Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."Receptors, Kainic Acid: A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.Status Epilepticus: A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Convulsants: Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools.Flurothyl: A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Kindling, Neurologic: The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures.Pentylenetetrazole: A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.Medulla Oblongata: The lower portion of the BRAIN STEM. It is inferior to the PONS and anterior to the CEREBELLUM. Medulla oblongata serves as a relay station between the brain and the spinal cord, and contains centers for regulating respiratory, vasomotor, cardiac, and reflex activities.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Epilepsy, Temporal Lobe: A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Quinolinic AcidsNitrergic Neurons: Nerve cells where transmission is mediated by NITRIC OXIDE.Ibotenic Acid: A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.Epilepsy: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)alpha-Methyltyrosine: An inhibitor of the enzyme TYROSINE 3-MONOOXYGENASE, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with PHEOCHROMOCYTOMA. (Martindale, The Extra Pharmacopoeia, 30th ed)Mossy Fibers, Hippocampal: Axons of certain cells in the DENTATE GYRUS. They project to the polymorphic layer of the dentate gyrus and to the proximal dendrites of PYRAMIDAL CELLS of the HIPPOCAMPUS. These mossy fibers should not be confused with mossy fibers that are cerebellar afferents (see NERVE FIBERS).Receptors, Glutamate: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.Vestibular Nuclei: The four cellular masses in the floor of the fourth ventricle giving rise to a widely dispersed special sensory system. Included is the superior, medial, inferior, and LATERAL VESTIBULAR NUCLEUS. (From Dorland, 27th ed)Glutamates: Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.PyrrolidinesNerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Quisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Periaqueductal Gray: Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.Quinolinic Acid: A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Anticonvulsants: Drugs used to prevent SEIZURES or reduce their severity.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Nystagmus, Physiologic: Involuntary rhythmical movements of the eyes in the normal person. These can be naturally occurring as in end-position (end-point, end-stage, or deviational) nystagmus or induced by the optokinetic drum (NYSTAGMUS, OPTOKINETIC), caloric test, or a rotating chair.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Hyperprolactinemia: Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8)Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Injections, Intraventricular: Injections into the cerebral ventricles.Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain.Dentate Gyrus: GRAY MATTER situated above the GYRUS HIPPOCAMPI. It is composed of three layers. The molecular layer is continuous with the HIPPOCAMPUS in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called GRANULE CELLS, whose AXONS pass through the polymorphic layer ending on the DENDRITES of PYRAMIDAL CELLS in the hippocampus.Pons: The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM.Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Behavior, Animal: The observable response an animal makes to any situation.6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.NADPH Dehydrogenase: A flavoprotein that reversibly oxidizes NADPH to NADP and a reduced acceptor. EC 1.6.99.1.QuinoxalinesAstrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)).

In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. (1/1468)

In vivo intracellular recording and labeling in kainate-induced epileptic rats was used to address questions about granule cell axon reorganization in temporal lobe epilepsy. Individually labeled granule cells were reconstructed three dimensionally and in their entirety. Compared with controls, granule cells in epileptic rats had longer average axon length per cell; the difference was significant in all strata of the dentate gyrus including the hilus. In epileptic rats, at least one-third of the granule cells extended an aberrant axon collateral into the molecular layer. Axon projections into the molecular layer had an average summed length of 1 mm per cell and spanned 600 microm of the septotemporal axis of the hippocampus-a distance within the normal span of granule cell axon collaterals. These findings in vivo confirm results from previous in vitro studies. Surprisingly, 12% of the granule cells in epileptic rats, and none in controls, extended a basal dendrite into the hilus, providing another route for recurrent excitation. Consistent with recurrent excitation, many granule cells (56%) in epileptic rats displayed a long-latency depolarization superimposed on a normal inhibitory postsynaptic potential. These findings demonstrate changes, occurring at the single-cell level after an epileptogenic hippocampal injury, that could result in novel, local, recurrent circuits.  (+info)

Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. (2/1468)

Synaptically released Zn2+ can enter and cause injury to postsynaptic neurons. Microfluorimetric studies using the Zn2+-sensitive probe, Newport green, examined levels of [Zn2+]i attained in cultured cortical neurons on exposure to N-methyl-D-asparte, kainate, or high K+ (to activate voltage-sensitive Ca2+ channels) in the presence of 300 microM Zn2+. Indicating particularly high permeability through Ca2+-permeable alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionic-acid/kainate (Ca-A/K) channels, micromolar [Zn2+]i rises were observed only after kainate exposures and only in neurons expressing these channels [Ca-A/K(+) neurons]. Further studies using the oxidation-sensitive dye, hydroethidine, revealed Zn2+-dependent reactive oxygen species (ROS) generation that paralleled the [Zn2+]i rises, with rapid oxidation observed only in the case of Zn2+ entry through Ca-A/K channels. Indicating a mitochondrial source of this ROS generation, hydroethidine oxidation was inhibited by the mitochondrial electron transport blocker, rotenone. Additional evidence for a direct interaction between Zn2+ and mitochondria was provided by the observation that the Zn2+ entry through Ca-A/K channels triggered rapid mitochondrial depolarization, as assessed by using the potential-sensitive dye tetramethylrhodamine ethylester. Whereas Ca2+ influx through Ca-A/K channels also triggers ROS production, the [Zn2+]i rises and subsequent ROS production are of more prolonged duration.  (+info)

Glutamate-, kainate- and NMDA-evoked membrane currents in identified glial cells in rat spinal cord slice. (3/1468)

The effect of L-glutamate, kainate and N-methyl-D-aspartate (NMDA) on membrane currents of astrocytes, oligodendrocytes and their respective precursors was studied in acute spinal cord slices of rats between the ages of postnatal days 5 and 13 using the whole-cell patch-clamp technique. L-glutamate (10(-3) M), kainate (10(-3) M), and NMDA (2x10(-3) M) evoked inward currents in all glial cells. Kainate evoked larger currents in precursors than in astrocytes and oligodendrocytes, while NMDA induced larger currents in astrocytes and oligodendrocytes than in precursors. Kainate-evoked currents were blocked by the AMPA/kainate receptor antagonist CNQX (10(-4) M) and were, with the exception of the precursors, larger in dorsal than in ventral horns, as were NMDA-evoked currents. Currents evoked by NMDA were unaffected by CNQX and, in contrast to those seen in neurones, were not sensitive to Mg2+. In addition, they significantly decreased during development and were present when synaptic transmission was blocked in a Ca2+-free solution. NMDA-evoked currents were not abolished during the block of K+ inward currents in glial cells by Ba2+; thus they are unlikely to be mediated by an increase in extracellular K+ during neuronal activity. We provide evidence that spinal cord glial cells are sensitive to the application of L-glutamate, kainate and transiently, during postnatal development, to NMDA.  (+info)

The distribution of neurons expressing calcium-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. (4/1468)

The superficial dorsal horn is a major site of termination of nociceptive primary afferents. Fast excitatory synaptic transmission in this region is mediated mainly by release of glutamate onto postsynaptic AMPA and NMDA receptors. NMDA receptors are known to be Ca2+-permeable and to provide synaptically localized Ca2+ signals that mediate short-term and long-term changes in synaptic strength. Less well known is a subpopulation of AMPA receptors that is Ca2+-permeable and has been shown to be synaptically localized on dorsal horn neurons in culture (Gu et al., 1996) and expressed by dorsal horn neurons in situ (Nagy et al., 1994; Engelman et al., 1997). We used kainate-induced cobalt uptake as a functional marker of neurons expressing Ca2+-permeable AMPA receptors and combined this with markers of nociceptive primary afferents in the postnatal rat dorsal horn. We have shown that cobalt-positive neurons are located in lamina I and outer lamina II, a region strongly innervated by nociceptors. These cobalt-positive neurons colocalize with afferents labeled by LD2, and with the most dorsal region of capsaicin-sensitive and IB4- and LA4-positive afferents. In contrast, inner lamina II has a sparser distribution of cobalt-positive neurons. Some lamina I neurons expressing the NK1 receptor, the receptor for substance P, are also cobalt positive. These neurons are likely to be projection neurons in the nociceptive pathway. On the basis of all of these observations, we propose that Ca2+-permeable AMPA receptors are localized to mediate transmission of nociceptive information.  (+info)

Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immunochemical/behavioral evidence. (5/1468)

Cells within the lateral hypothalamic area (LHA) are important in eating control. Glutamate or its analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), elicit intense eating when microinjected there, and, conversely, LHA-administered NMDA receptor antagonists suppress deprivation- and NMDA-elicited eating. The subunit composition of LHA NMDA receptors (NMDA-Rs) mediating feeding, however, has not yet been determined. Identifying this is important, because distinct second messengers/modulators may be activated by NMDA-Rs with differing compositions. To begin to address this, we detected LHA NR2A and NR2B subunits by immunoblotting and NR2B subunits by immunohistochemistry using subunit-specific antibodies. To help determine whether NMDA-Rs mediating feeding might contain these subunits, we conducted behavioral studies using LHA-administered ifenprodil, an antagonist selective for NR2A- and/or NR2B-containing NMDA-Rs at the doses we used (0.001-100 nmol). Ifenprodil maximally suppressed NMDA- and deprivation-elicited feeding by 63 and 39%, respectively, but failed to suppress KA-elicited eating, suggesting its actions were behaviorally specific. Collectively, these results suggest that LHA NMDA-Rs, some of which contribute to feeding control, are composed of NR2A and/or NR2B subunits, and implicate NR2A- and/or NR2B-linked signal transduction in feeding behavior.  (+info)

Subtype-specific effects of lithium on glutamate receptor function. (6/1468)

We report that substitution of sodium with lithium (Li+) in the extracellular solution causes subtype-specific changes in the inward and outward currents of glutamate receptors (GluRs), without a shift in reversal potential. Li+ produces an increase of inward and outward currents of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors and decreases in the currents of kainate (KA) and N-methyl-D-aspartate receptors. The greatest effect of Li+ was observed with GluR3. A concentration-response curve for GluR3 reveals that the potentiation caused by Li+ is greatest at saturating agonist concentrations. GluR1, which shows no potentiation by Li+ at 100 microM KA, shows a small but significant potentiation at saturating KA and glutamate concentrations. The effects of Li+ on outward current, where Li+ is not the primary charge carrier, and the lack of reversal potential shift argue for a mechanism of potentiation not associated with Li+ permeation. This potentiation of current is specific for Li+ because rubidium, although causing an increase of inward current, shifted the reversal potential and did not increase outward current. The effects of Li+ are different for KA, a weak desensitizing agonist, and glutamate, a strong desensitizing agonist, suggesting that Li+ might interact with a mechanism of desensitization. By using cyclothiazide (CTZ) to reduce desensitization of GluR3, we find that for low concentrations of KA and glutamate potentiation of the response by a combination of CTZ and Li+ is no greater than by CTZ or Li+ alone. However, at high concentrations of agonist, the potentiation of the response by a combination of CTZ and Li+ is significantly greater than by CTZ or Li+ alone. This potentiation was additive for glutamate but not for KA. At high agonist concentration in the presence of CTZ, the intrinsically lower desensitization produced with KA-evoked responses may preclude Li+ from potentiating the current to the same degree as it can potentiate glutamate-evoked responses. The additive effects of CTZ and Li+ were unique to the flop variant of GluR3.  (+info)

Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. (7/1468)

A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in approximately 74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of NMDA receptors in the recurrent pathway may contribute to seizure propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal rats, where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant.  (+info)

Role of the Botzinger complex in fastigial nucleus-mediated respiratory responses. (8/1468)

We have reported that the phrenic neurogram (PN) is modulated by stimulation of the fastigial nucleus (FN) of the cerebellum. The present study was undertaken to search for brainstem site(s) involved in the FN efferent pathway to modulate phrenic nerve activities. Experiments were performed on 35 anesthetized, paralyzed, and ventilated cats, using the PN as the index of the respiratory motor output. Results showed that bilateral electrolytic lesions of the red nucleus (RN), the paramedian reticular nucleus (PRN), or the pontine respiratory group (PRG) had little effect on the ability of FN stimulation to modulate the respiratory output. However, the modulation was abolished by bilateral electrolytic lesions of the Botzinger complex (BotC). Further studies showed that bilateral chemical inactivation of BotC neurons produced by topical microinjection of kainic acid or cobalt chloride failed to abolish the modulation. We concluded that fibers of passage, not synapses or cell bodies in the BotC, were involved in the modulatory effect of FN stimulation on the PN. The RN, PRN, and PRG appear not to be important in the neural circuitry responsible for the FN modulation of the phrenic activity.  (+info)

  • Kainic acid is a direct agonist of the glutamic kainate receptors and large doses of concentrated solutions produce immediate neuronal death by overstimulating neurons to death. (wikipedia.org)
  • Thus, in large, concentrated doses kainic acid can be considered a neurotoxin, and in small doses of dilute solution kainic acid will chemically stimulate neurons. (wikipedia.org)
  • An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid," Autophagy , vol. 4, no. 2, pp. 214-226, 2008. (hindawi.com)
  • Local injections of kainic acid, which destroyed cholinergic and GABA neurons in the caudatoputamen and in the nucleus accumbens, caused a rapid (70-90%) decrease in the soluble guanylate cyclase and a slower 50‐60% fall in the particulate guanylate cyclase in these nuclei. (deepdyve.com)
  • In this study, we investigated a role of COX isoforms (COX-1 and COX-2) in kainic acid-induced neuronal death in cultured murine cortical or hippocampal neurons. (elsevier.com)
  • In primary cortical neurons, both indomethacin (COX-1/-2 nonselective inhibitor) and aspirin (COX-1 preferential inhibitor) reduced basal and kainic acid-induced PGE 2 production significantly and prevented neuronal cell death after kainic acid treatment. (elsevier.com)
  • In hippocampal neurons, however, COX-2 inhibitors prevented both kainic acid-induced neuronal death and PGE 2 production. (elsevier.com)
  • In conclusion, we suggest that the release of PGE 2 induced by kainic acid occurred through COX-1 activity rather than COX-2 in cortical neurons. (elsevier.com)
  • The inhibition of PGE 2 release by COX-1 inhibitors prevented kainic acid-induced cortical neuronal death, while in the hippocampal neurons, COX-2 inhibitors prevented kainic acid-induced PGE 2 release and hippocampal neuronal death. (elsevier.com)
  • Bromodeoxyuridine labeled neurons increased at least 6-fold on the side ipsilateral to the kainic acid injection compared to controls, but significantly, were also increased, by at least 3-fold on the side contralateral to the injection. (cf.ac.uk)
  • In this article we cultured axotomized rat dorsal root ganglion neurons to investigate the effects of corticosterone and a glutamate receptor agonist kainic acid on neurite outgrowth. (elsevier.com)
  • Western blot analysis and immunocytochemical studies revealed an increase of expressions of both TrkA and growth-associated protein GAP-43 in dorsal root ganglion neurons with combined treatment of corticosterone and kainic acid. (elsevier.com)
  • Immunocytochemistry showed that corticosterone+kainic acid increase nerve growth factor immunoreactivity in dorsal root ganglion neurites and enhance GAP-43 immunointensity in dorsal root ganglion neurons. (elsevier.com)
  • Here we further studied in vivo the sensitivity of the hippocampal CA1 neurons in response to CTZ in epileptogenesis in comparison with two other classic convulsants of kainic acid (KA) and pentylenetetrazol (PTZ). (naver.com)
  • Therefore, the most effective ablation studies are performed in comparison to a sham lesion that duplicates all the steps of producing a brain lesion except the one that actually causes the brain damage, that is, injection of kainic acid or administration of an electrical shock. (wikipedia.org)
  • The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). (nih.gov)
  • We now investigate the effect of intra-amygdaloid injection of kainic acid, as another model of temporal lobe epilepsy, focusing on epileptogenesis, spike-and-wave discharges (SWDs), and the transition from basal to SWD states in GAERS. (jneurosci.org)
  • SWDs and increases in power of the delta, alpha, and beta frequency ranges during the transition period disappeared after the kainic acid injection for 1-3 d and gradually reappeared. (jneurosci.org)
  • We have further evaluated the interplay between absence epilepsy and limbic epilepsy by using intra-amygdaloid injection of kainic acid in adult GAERS as another model of temporal lobe epilepsy ( Sperk, 1994 ) to compare with intra-amygdaloid kindling. (jneurosci.org)
  • Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. (biomedsearch.com)
  • Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. (biomedsearch.com)
  • The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. (biomedsearch.com)
  • Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. (biomedsearch.com)
  • GFAP levels were induced 3 days after kainic acid injection in brain regions where MMP-2 was elevated. (ovid.com)
  • These data demonstrate that MMP-9 and MMP-2 are differentially expressed with respect to time after kainic acid injection, and suggest that they are regulated by convulsion and/or neurodegenerative-associated mechanisms, respectively. (ovid.com)
  • In this study, we evaluated the expression of APC and its association with β-catenin signaling pathway, following the induction of an excitotoxic lesion by kainic acid (KA) injection, which cause pyramidal cell degeneration. (springer.com)
  • Intraventricular injection of kainic acid produced a characteristic necrosis in the hippocampal CA3 region of adult rabbits. (elsevier.com)
  • The animals were sacrificed by decapitation on the 1st, 4th and 10th day after injection of the kainic acid. (ndsl.kr)
  • 3. After injection of the kainic acid the neurites of the inner plexiform layer were swollen at the first, and thereafter those changes were gradually disappeared until the 10th day. (ndsl.kr)
  • We report here for the first time that granule cell neurogenesis is increased bilaterally 1 week after a single unilateral intracerebroventricular injection of kainic acid. (cf.ac.uk)
  • Injection of kainic acid (KA) can induce neurodegeneration and epilepsy in the experimental study. (tci-thaijo.org)
  • Here, we investigate hippocampal changes using a mouse model that receive a single kainic acid-intracerebral ventricle injection. (biomedcentral.com)
  • The effects of caspase 3 inhibition on these changes were detected during a period of 1 to 7 days post kainic acid injection. (biomedcentral.com)
  • The co-injection of caspase 3 inhibitor did not rescue kainic acid-mediated neurodegeneration but seriously and reversibly disturb the structural integrity of axon and dendrite. (biomedcentral.com)
  • The kainic acid-induced events include microglia activation, the proliferation of radial glial cells, neurogenesis, and calcineurin A cleavage were significantly inhibited by the co-injection of caspase 3 inhibitor, suggesting the direct involvement of caspase 3 in these events. (biomedcentral.com)
  • Walaas, Ivar 1981-01-01 00:00:00 Abstract: The activity of soluble and particulate guanylate cyclase (EC 4.6.1.2) has been compared with the distribution of neurotransmitter candidates in three rat forebrain nuclei, and the effects of local kainic acid injections into these nuclei have been tested. (deepdyve.com)
  • abstract = "Kainic acid (KA) selectively damages afferent synapses that innervate, in chickens, mainly tall hair cells. (elsevier.com)
  • abstract = "The distribution of [3H]kainic acid (KA) binding sites in the rat CNS was determined by in vitro autoradiography. (nebraska.edu)
  • antiworming agent neuroscience research neurodegenerative agent modeling of epilepsy modeling of Alzheimer's disease Dihydrokainic acid Domoic acid Kainate receptor Carlson, Neil R. Physiology of Behavior. (wikipedia.org)
  • Ben-Ari, Y., Tremblay, E., and Ottersen, 0.P., 1980, Injections of kainic acid into the amygdaloid complex of the rat: an electrographic, clinical and histological study in relation to the pathology of epilepsy, Neuroscience 5: 515. (springer.com)
  • kainic acid: mechanisms and relevance to human temporal lobe epilepsy, Neuroscience 14:375. (springer.com)
  • To investigate the pathophysiological role of phospholipase D (PLD)-mediated signaling, changes in the expression of the PLD isozymes PLD1 and PLD2 were investigated in the rat kainic acid (KA) model of human temporal lobe epilepsy. (elsevier.com)
  • The potential for this disease was first recognized in a human case study of temporal lobe epilepsy after the 1987 amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic epileptic syndrome in California sea lions through investigation of a series of domoic acid poisoning cases between 1998 and 2006. (mdpi.com)
  • Gluck MR, Jayatilleke E, Shaw S, Rowan AJ, Haroutunian V. CNS oxidative stress associated with the kainic acid rodent model of experimental epilepsy. (tci-thaijo.org)
  • kainic acid (KA) is one of the most common chemoconvulsants used to create SE models of temporal lobe epilepsy (TLE). (biomedcentral.com)
  • The present study used continuous electroencephalography ( EEG ) to evaluate the therapeutic efficacy of RG in intrahippocampal kainic acid (IHKA) animal model of temporal lobe epilepsy . (bvsalud.org)
  • In recent years, kainic acid has been used as a research tool to study human neurological conditions such as epilepsy and Alzheimer's disease. (ucsd.edu)
  • Sensitive indices of neural injury were used to evaluate the time course of kainic acid (KA)-induced hippocampal damage in adult C57BL/6J mice (4 months), a strain previously reported to be resistant to kainate-induced neurotoxicity. (cdc.gov)
  • Kainic acid hyperphosphorylates tau via inflammasome activation in MAPT transgenic mice. (alzforum.org)
  • IL-18 deficiency aggravates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice due to an overcompensation by IL-12. (tci-thaijo.org)
  • Seventy adult male KM mice were subjected to microinjections into the hippocampus of kainic acid (KA) or 500, 1000, or 2000 µg/ml tunicamycin (TM). (bvsalud.org)
  • Curcumin attenuates the kainic acid-induced hippocampal cell death in the mice. (greenmedinfo.com)
  • Supraphysiological levels of the stress hormone corticosterone attenuate blood-brain barrier disruption and microglial activation in hippocampus of C57BL/6J mice treated with kainic acid. (cdc.gov)
  • Kainic acid intoxication in C57BL/6J mice causes neuronal damage and the activation of glial cells. (cdc.gov)
  • Control and implanted mice were injected intraperitoneally with saline or 25 mg/kg kainic acid, and sacrificed at 1, 3, 6, and 12 hours post treatment. (cdc.gov)
  • Older Abr;Bcr -deficient mice show spontaneous mid-brain glial hypertrophy, which can further be markedly enhanced by kainic acid. (biologists.org)
  • Kainic acid injections directly into the cerebellum destroy Purkinje, stellate, basket and Golgi II cells selectively with much less damage to granule cells. (elsevier.com)
  • Following the IHKA injections , one group received treatments of RG (250 mg/kg/day) for 4 weeks (RG group, n=7) while another group received valproic acid (VPA, 30 mg/kg/day) (VPA group, n=7). (bvsalud.org)
  • Franck, JE & Schwartzkroin, PA 1984, ' Immature rabbit hippocampus is damaged by systemic but not intraventricular kainic acid ', Developmental Brain Research , vol. 13, no. 2, pp. 219-227. (elsevier.com)
  • A team of scientists at Scripps Institution of Oceanography at the University of California San Diego and the J. Craig Venter Institute ( JCVI ) has developed a new way to produce kainic acid, a natural seaweed neurochemical and powerful reagent used in brain research. (ucsd.edu)
  • In a new study published April 17 in the journal Angewandte Chemie International Edition , the scientists were able to sequence the genome of a seaweed known to produce kainic acid, and they identified the enzymes responsible for production of the natural chemical. (ucsd.edu)
  • This biotransformation approach allows us to quickly produce kainic acid in a cheaper and more environmentally friendly way than traditional chemical synthesis. (ucsd.edu)
  • Dr. Moore's lab set out to identify the genes that code for the production of kainic acid in red seaweed and found that these genes enabled the seaweed to produce kainic acid in only two steps. (newswise.com)
  • The objective of this study was to determine whether MMPs are expressed in various regional areas of rat brain after administration of the neurotoxin, kainic acid. (ovid.com)
  • Their research builds upon the team's recent work on discovering the genetic origin of domoic acid, a potent neurotoxin produced by planktonic microalgae. (ucsd.edu)
  • The kit contains (S)-AMPA, ( ab120005 ), (S)-5-Fluorowillardiine hydrochloride ( ab120399 ), Cyclothiazide ( ab120061 ), Aniracetam ( ab120316 ), Kainic acid ( ab120100 ), (S)-5-Iodowillardiine hydrochloride ( ab120401 ), NMDA ( ab120052 ) and D-serine ( ab120048 ). (abcam.com)
  • Postnatal development of kainic acid binding sites in the limbic system, Neuroscience 13: 1095. (springer.com)
  • Hilmas et al 2001 J. of Neuroscience) Kynurenic acid may modulate the synaptic transmission through blockade of the alpha 7 nicotine cholinergic rezeptors (nACh), while7nChRs). (shakyradunn.com)
  • Recently, Dr. Moore discovered a faster and more environmentally friendly way to synthesize kainic acid-a compound produced by some types of red seaweed-that's valuable for neuroscience research. (newswise.com)
  • The neurotrophic effect of corticosterone and kainic acid was attenuated by the receptor tyrosine kinase A (TrkA) inhibitor AG-879. (elsevier.com)
  • 3APS) protects from the convulsant and cytotoxic effect of systemically administered kainic acid. (webmd.com)
  • Here, we present the concept of domoic acid epileptic disease as a delayed manifestation of domoic acid poisoning and review the state of knowledge for this disease state in affected humans and sea lions. (mdpi.com)
  • We now define domoic acid epileptic disease as distinct consequence of domoic acid poisoning that occurs in the absence of domoic acid. (mdpi.com)
  • However, in the case of domoic acid, we use the term "disease" because it is caused by a known external factor with a defined sequence of events and course of prognosis. (mdpi.com)
  • This concept report focuses on those essential characteristics of domoic acid poisoning that lead to epileptic disease drawing on case studies in humans and sea lions and a rat model to elucidate the structural basis specific to domoic acid epileptic maturation. (mdpi.com)
  • The domoic acid study helped the scientists develop a hypothesis for how a chemical compound like kainic acid is formed within a living organism-in this case seaweed-in a process known as biosynthesis. (ucsd.edu)
  • Supply shortages beginning in 2000 have caused the cost of kainic acid to rise significantly. (wikipedia.org)
  • Worldwide shortages of the seaweed natural product in 2000 prompted researchers to use chemical synthetic versions of kainic acid. (ucsd.edu)
  • These results are generally in conflict with those obtained by many researchers using the activity of the GABA synthetic enzyme glutamic acid decarboxylase (GAD) as a measure of GABA levels. (osu.edu)
  • Glutamic acid decarboxylase mRNA in rat brain: regional distribution and effects of intrastriatal kainic acid. (umassmed.edu)
  • Kainic acid lesions produce a 65-70% decrease in high affinity [ 3 H]GABA uptake into synaptosomal fractions and a similar decrease in glutamic acid decarboxylase with a 50% reduction in endogenous GABA. (elsevier.com)
  • Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. (stanford.edu)
  • The effect of alcohols (ethanol, 1-propanol, propylene glycol, glycerin, sucrose) on the phase behavior and emulsification of sucrose stearic acid ester (SSE)/water/edible vegetable oil (EVO) systems was investigated. (bireme.br)
  • Kainic acid (KA) exposure causes neuronal degeneration featured by Alzheimer-like tau hyperphosphorylation and memory deficits. (frontiersin.org)
  • Alternatively, the kainic acid-mediated astrogliosis is not caspase 3-dependent, although caspase 3 cleavage of glial fibrillary acidic protein occurred. (biomedcentral.com)
  • Home Research Outputs Distribution of GABA immunoreactivity in kainic acid-treated. (lu.se)
  • Application of kainic acid to the neostriatum caused a dose-dependent release of GABA both locally and, at the same time, from the ipsilateral substantia nigra. (ox.ac.uk)
  • Direct application of kainic acid to the substantia nigra caused a DNQX-sensitive local release of GABA. (ox.ac.uk)