Focal and secondarily generalised convulsive status epilepticus induced by thiocolchicoside in the rat.
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The objective of this study was to document the convulsant properties of thiocolchicoside in rats, and to characterise the electroclinical pattern of epileptic seizures. Experiments were carried out in three groups of male Wistar rats: in group A, thiocolchicoside was applied topically to the pia, or given by microinjection to the cerebral cortex (2 microg/microl); in group B, the drug was administered parenterally (6 mg/kg) to rats with minimal lesions of the dura and arachnoid membranes; in group C, thiocolchicoside was administered parenterally (up to 12 mg/kg) to intact rats. In all animals, electroclinical activity was continuously monitored for at least 3 hours after thiocolchicoside injection or application. In group A, electrographic and behavioural activity of focal motor seizures occurred in 100% of animals, developing into a focal status epilepticus; in group B, a multifocal epileptic pattern with secondary generalisation, clinically characterised by clonic or tonic-clonic seizures occurred in 100% of animals, until a secondarily generalised convulsive status epilepticus; in group C, none of animals showed either electrographic or behavioural seizure activity. Our study documents that thiocolchicoside has a powerful convulsant activity in the rat, perhaps due to an antagonistic interaction of the compound with a cortical subtype of the GABA(A) receptor. (+info)
Intrathecal 4-hydroperoxycyclophosphamide: neurotoxicity, cerebrospinal fluid pharmacokinetics, and antitumor activity in a rabbit model of VX2 leptomeningeal carcinomatosis.
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Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4-hydroperoxycyclophosphamide (4-HC) in the rabbit and the activity of i.t. 4-HC in a VX2 rabbit model of leptomeningeal carcinomatosis to evaluate the potential use of 4-HC in the treatment of leptomeningeal tumors. Toxicity studies examined 4-HC doses ranging from 0.5 to 6.0 mumol administered by intraventricular injection weekly for 4 to 8 weeks. Clinical or histological neurotoxicity was not observed in rabbits treated with < 1.0 mumol 4-HC for 4 weeks. Clinical toxicity, characterized by lethargy, weight loss, seizures, or death, was apparent at doses > 2.0 mumol. Vasculitis of superficial arteries was observed in rabbits treated with > 1.0 mumol 4-HC. In cerebrospinal fluid pharmacokinetic studies, the mean drug half-life after intraventricular or intralumbar administration was 24.3 and 18.2 min. Regional inequities in drug exposure were apparent as area under the clearance curve values for cerebrospinal fluid distant from the injection site were lower than those of proximate sites (P < 0.001). Weekly intraventricular treatment of VX2 leptomeningeal tumor-bearing rabbits with 0.5 or 1.0 mumol of 4-HC resulted in an increased life span of 22.5 and 35%, respectively. These results indicate that i.t. 4-HC, at doses lower than those producing neurotoxicity in the rabbit, is effective treatment for VX2 leptomeningeal carcinomatosis. (+info)
Tridimensional architecture of the collagen element in the arachnoid granulations in humans: a study on scanning electron microscopy.
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The arachnoid granulations of adult individual of both sexes were studied through scanning electron microscopy. The dura mater and arachnoid meninges of individuals were collected at the Service of Death Verification of Sao Paulo - USP and fixed in Karnovsky solution. After this period the material was prepared for analysis in electron microscope. Our results demonstrated that the arachnoid granulations are formed by a pedicle, body and apex, being surrounded by a capsule of connective tissue, which in turn is composed of, basically, bundles of collagen fibers that line pores of different shapes and sizes. The smaller pores are lined by tiny bundles and are located at the apical region of the granulation and the larger are lined by thicker bundles and are located at the lateral regions. In the body we verified that the bundles of collagen fibers compose a fibrous meshwork and in some regions these bundles have circular orientation, forming pores similar to those found at the region of the capsule. (+info)
Regulation of rat pial arteriolar smooth muscle relaxation in vivo through multidrug resistance protein 5-mediated cGMP efflux.
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Multidrug resistance protein 5 (MRP5) has been linked to cGMP cellular export in peripheral vascular smooth muscle cells (VSMCs) and is widely expressed in brain vascular tissue. In the present study, we examined whether knockdown of MRP5 in pial arterioles [via antisense oligodeoxynucleotide (ODN) applications] affected nitric oxide (NO)/cGMP-induced dilations. The antisense or (as a control) missense ODN was applied to the cortical surface approximately 24 h before study via closed cranial windows. The efficacy of the antisense vs. missense ODN in eliciting selective reductions in MRP5 expression was confirmed by analysis of MRP5 mRNA in pial tissue. Unexpectedly, in initial studies, a significantly lower maximal pial arteriolar diameter increase in the presence of the NO donor S-nitrosoacetylpenicillamine (SNAP) was seen in the antisense vs. missense ODN-treated rats (35 vs. 48% diameter increase, respectively). It was suspected that this related to a reduced vascular smooth muscle cell sensitivity to cGMP due to prolonged exposure to increased intracellular cGMP levels elevated by overnight restriction of cGMP efflux. That postulate was supported by a finding of a diminished vasodilating response to the cGMP-dependent protein kinase-activating cGMP analog 8-p-chlorophenylthio-cGMP in antisense vs. missense ODN-treated rats. To prevent desensitization, additional rats were studied in the presence of chronic NOS inhibition via Nomega-nitro-L-arginine. In the NO synthase (NOS)-inhibited rats, the maximal SNAP response was much higher in the antisense (62% increase) vs. the missense ODN (40% increase) group. A similar result was obtained when monitoring responses to the soluble guanylyl cyclase-activating drugs YC-1 and BAY 41-2272. Moreover, in the presence of NOS inhibition, the normal SNAP-induced rise in periarachnoid cerebrospinal fluid cGMP levels, which reflects cGMP efflux, was absent in the antisense ODN-treated rats, a finding consistent with loss of MRP5 function. In conclusion, if one minimizes the confounding effects of basal cGMP production, a clearer picture emerges, one that indicates an important role for MRP5-mediated cGMP efflux in the regulation of NO-induced cerebral arteriolar relaxation. (+info)
The sphenoparietal sinus of breschet: does it exist? An anatomic study.
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BACKGROUND AND PURPOSE: The termination of the superficial middle cerebral vein is classically assimilated to the sphenoid portion of the sphenoparietal sinus. This notion has, however, been challenged in a sometimes confusing literature. The purpose of the present study was to evaluate the actual anatomic relationship existing between the sphenoparietal sinus and the superficial middle cerebral vein. METHODS: The cranial venous system of 15 nonfixed human specimens was evaluated by the corrosion cast technique (12 cases) and by classic anatomic dissection (three cases). Angiographic correlation was provided by use of the digital subtraction technique. RESULTS: The parietal portion of the sphenoparietal sinus was found to correspond to the parietal portion of the anterior branch of the middle meningeal veins. The sphenoid portion of the sphenoparietal sinus was found to be an independent venous sinus coursing under the lesser sphenoid wing, the sinus of the lesser sphenoid wing, which was connected medially to the cavernous sinus and laterally to the anterior middle meningeal veins. The superficial middle cerebral vein drained into a paracavernous sinus, a laterocavernous sinus, or a cavernous sinus but was never connected to the sphenoparietal sinus. All these venous structures were demonstrated angiographically. CONCLUSION: The sphenoparietal sinus corresponds to the artificial combination of two venous structures, the parietal portion of the anterior branch of the middle meningeal veins and a dural channel located under the lesser sphenoid wing, the sinus of the lesser sphenoid wing. The classic notion that the superficial middle cerebral vein drains into or is partially equivalent to the sphenoparietal sinus is erroneous. Our study showed these structures to be independent of each other; we found no instance in which the superficial middle cerebral vein was connected to the anterior branch of the middle meningeal veins or the sinus of the lesser sphenoid wing. The clinical implications of these anatomic findings are discussed in relation to dural arteriovenous fistulas in the region of the lesser sphenoid wing. (+info)
Effect of craniocervical decompression on peak CSF velocities in symptomatic patients with Chiari I malformation.
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BACKGROUND AND PURPOSE: Peak CSF velocities detected in individual voxels in the subarachnoid space in patients with Chiari I malformations exceed those in similar locations in the subarachnoid space in healthy subjects. The purpose of this study was to test the hypothesis that the peak voxel velocities are decreased by craniocervical decompression. METHODS: A consecutive series of patients with symptomatic Chiari I malformations was studied before and after craniocervical decompression with cardiac-gated, phase contrast MR imaging. Velocities were calculated for each voxel within the foramen magnum at 14 time points throughout the cardiac cycle. The greatest velocities measured in a voxel during the cephalad and caudad phases of CSF flow through the foramen magnum were tabulated for each patient before and after surgery. The differences in these velocities between the preoperative and postoperative studies were tested for statistical significance by using a single-tailed Student's t test of paired samples. RESULTS: Eight patients with a Chiari I malformation, including four with a syrinx, were studied. Peak caudad velocity diminished after craniocervical decompression in six of the eight patients, and the average diminished significantly from 3.4 cm/s preoperatively to 2.4 cm/s postoperatively (P =.01). Peak cephalad velocity diminished in six of the eight cases. The average diminished from 6.9 cm/s preoperatively to 3.9 cm/s postoperatively, a change that nearly reached the significance level of.05 (P =.055). CONCLUSION: Craniocervical decompression in patients with Chiari I malformations decreases peak CSF velocities in the foramen magnum. The study supports the hypothesis that successful treatment of the Chiari I malformation is associated with improvement in CSF flow patterns. (+info)
Progressive adhesive arachnoiditis following spinal anesthesia.
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Neurological complications-some of them serious-sometimes occur following spinal anesthesia. In the majority of the relatively few cases in which they occur, they are caused by factors which can be obviated.Rigid adherence to defined safeguards will reduce the incidence of complications and overcome most of the objections to the procedure. (+info)
Detailed MR imaging anatomy of the abducent nerve: evagination of CSF into Dorello canal.
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BACKGROUND AND PURPOSE: The abducent nerve is difficult to identify reliably and consistently with conventional radiologic techniques. In this study, a 3D fast asymmetrical spin-echo MR imaging technique was used to obtain detailed images of the abducent nerve in normal volunteers. METHODS: The 3D fast asymmetrical spin-echo MR protocol was used to image the abducent nerves in 24 normal volunteers by using a 1-mm section thickness in the tilted axial and parasagittal planes. The microanatomy of the abducent nerve within Dorello's canal was also demonstrated in a cadaver study. RESULTS: In 24 normal volunteers, the anatomy of 47 abducent nerves was clearly depicted on MR images. The length of the cisternal segment of the abducent nerve, extending from the brain stem to its dural foramina, ranged from 6.7 to 19.6 mm (mean, 13.1 mm). The abducent nerves were at an angle of 5 to 90 degrees (mean, 24.5 degrees) to the clivus. CSF evagination was detected in the region of Dorello's canal in 36 (77%) of 47 abducent nerves. The length of CSF evagination varied: 0.9 mm in five nerves, 1.0 to 1.9 mm in 18 nerves, 2.0 to 2.9 mm in eight nerves, and 3.0 mm or more in five nerves. Histologic examination of serial sections of the abducent nerve revealed that the petroclival segment of the nerve was covered by an envelope composed of an arachnoid cell layer. CONCLUSION: The course of the abducent nerve was reliably identified using the 3D fast asymmetrical spin-echo MR protocol and a histologically proven arachnoid envelope around the petroclival segment of the nerve was shown as CSF evagination into Dorello's canal by MR imaging. (+info)