The meninges is a source of retinoic acid for the late-developing hindbrain.
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One general function for retinoic acid (RA) is pattern organization in the CNS. This regulatory factor has an essential role in spinal cord motor neuron and early posterior hindbrain development. In the anterior CNS, however, there is only a limited number of foci of RA synthesis, and less attention has been placed on regions such as the anterior hindbrain where RA synthesizing enzymes are absent. This study shows that a rich source of RA lies around the hindbrain from the RA synthetic enzyme retinaldehyde dehydrogenase-2 (RALDH2) present in the surrounding meninges and mesenchyme by embryonic day 13. RALDH2 is not distributed uniformly throughout the meninges but is restricted to territories over the developing hindbrain, suggesting that RA signaling may be localized to those regions. Further regulation of RA signaling is provided by the presence of a RA sink in the form of the CYP26B1 RA catabolic enzyme expressed in deeper regions of the brain. As a guide to the neural anatomy of hindbrain RA signaling, we used a mouse transgenic for a lacZ reporter gene driven by a RA response element (RAREhsplacZ) to identify regions of RA signaling. This reporter mouse provides evidence that RA signaling in the hindbrain after embryonic day 13 occurs in the regions of the cerebellum and precerebellar system adjacent to sources of RA, including the inferior olive and the pontine nuclei. (+info)
Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats.
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The present study provides the first evidence that signaling occurs between B-ephrins and EphB receptors in the adult CNS in response to injury. Specifically, our combined histological and biochemical data indicate that two members of the B-class of ephrins and Eph receptors, ephrin-B2 and EphB2, are expressed by astrocytes and meningeal fibroblasts, respectively, in the adult spinal cord. In response to thoracic spinal cord transection lesions, ephrin-B2 and EphB2 protein levels exhibit an initial decrease (1 d after lesion), followed by a significant increase by day 14. Immunohistochemical data indicate that ephrin-B2 is expressed by reactive CNS astrocytes, and EphB2 is present on fibroblasts invading the lesion site from the adjacent meninges. During the first 3 d after injury, there is intermingling of ephrin-B2-expressing reactive astrocytes at the lesion surface with EphB2-containing fibroblasts that is concurrent with bidirectional activation (phosphorylation) of ephrin-B2 and EphB2. By 7 d, both cell types are establishing restricted cellular domains containing dense networks of cells and interweaving processes. This astroglial-meningeal fibroblast scar is fully developed by day 14 when there is strict segregation of ephrin-B2-expressing astrocytes from EphB2-positive meningeal fibroblasts. These morphological changes are concomitant with a simultaneous decrease in ephrin-B2 and EphB2 activation. These observations provide strong evidence that cell contact-mediated bidirectional signaling between ephrin-B2 on reactive astrocytes and EphB2 on meningeal fibroblasts is an early event in the cellular cascades that result in the development of the glial scar and the exclusion of meningeal fibroblasts from the injured spinal cord. (+info)
CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges.
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1. The effects of intravenously administered 5-HT1B receptor agonists were examined on c-fos like immunoreactivity, an indicator of neuronal activation, within the brain stem. C-fos was induced by injecting an algesic, vasoconstrictor substance (0.3 ml of autologous blood) or a pro-inflammatory molecule, carrageenin (1 mg in 0.1 ml saline) into the cisterna magna of pentobarbitone-anaesthetized Sprague-Dawley rats and was visualized in serial sections (50 micrometers) by use of a polyclonal antiserum. 2. As previously reported, the injection of blood caused significant labelling within laminae I, IIo of the trigeminal nucleus caudalis, a major nociceptive brain stem nucleus, as well as within nucleus of the solitary tract and area postrema. A similar pattern of expression with fewer cells per section was detected after carrageenin instillation. The number of expressing cells was reduced by 54% in trigeminal nucleus caudalis but not within the nucleus of the solitary tract or area postrema when blood was injected in adult rats neonatal capsaicin treatment. 3. Pretreatment with 5-HT1 agonists with some selectivity for the 5-HT1B receptor, CP-93,129 (460 nmol kg-1 x 2, i.v.), sumatriptan (720 nmol kg-1 x 2, i.v.) or dihydroergotamine (86 nmol kg-1 x 2, i.v.) reduced positive cells by 39%, 31%, and 33% respectively in trigeminal nucleus caudalis but not in nucleus of the solitary tract or area postrema after blood instillation. Pretreatment with the analgesic morphine (15 mumol kg-1, s.c.) also decreased the number of positive cells by 63% in trigeminal nucleus caudalis. 4. CP-93,129 (460 nmol kg-1 x 2, i.v.) reduced the number of c-fos labelled cells by 47% within lamina I, IIo after carrageenin instillation. 5. Drug-induced blockade appeared to be tissue-dependent. Pretreatment with sumatriptan (720 nmol kg-1 x 2, i.v.) did not block c-fos expression in trigeminal nucleus caudalis following formalin application to the nasal mucosa.6. Drug-induced blockade may be mediated by an action on primary afferent (trigeminovascular) fibres in as much as CP-93,129 (460 nmol kg-' x 2, i.v.) did not reduce the number of expressing cells within the trigeminal nucleus caudalis following blood instillation in rats treated as neonates with capsaicin.7. We infer from these results that the analgesic actions of agonists at 5-HTB receptors (the receptor subtype analogous to 5-HTID in man) need not depend upon the presence of vasodilatation and, that 5-HTID receptor-mediated blockade of neurotransmission contributes significantly to the analgesic effects of these drugs in headache.8. Based on the demonstrated effects of 5-HTB/D agonists against the actions of two chemicallyunrelated meningeal stimulants, we suggest that treatment with 5-HTID agonists may be useful for the alleviation of pain in other headache conditions associated with meningeal irritation. Bacterial, viral(including AIDS meningovascular inflammation) and other forms of chemical meningitis merit further investigation. (+info)
Meningeal carcinomatosis.
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Meningeal carcinomatosis without gross tumour in the substance of the brain or spinal cord has been reported rarely. Two cases observed at the Victoria General Hospital, Halifax, presented a bizarre clinical picture consisting of signs of meningeal irritation without fever, and psychotic behaviour. Examination of the cerebrospinal fluid revealed low sugar concentration and increased pressure, protein and cells. In one case these cells were readily identified as malignant on stained smears. At autopsy the surfaces of the cerebral hemispheres, cerebellum and brain stem were covered by an opalescent film and on section the subarachnoid space was densely packed with malignant cells. Both primary tumours were adenocarcinomas, one originating in the gallbladder and one in the rectum. The diagnosis of meningeal carcinomatosis must be considered in patients presenting with profound mental changes and meningeal irritation without fever. Diagnosis may be confirmed by cytological examination of the cerebrospinal fluid. The primary tumour is most commonly an adenocarcinoma. There is no satisfactory treatment available. (+info)
CARCINOMATOSIS OF THE MENINGES.
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Some clinical and pathological features of carcinomatosis of the meninges are reviewed along with a report of four cases. This condition usually presents in middle age as a subacute meningitis with cranial nerve involvement, but the diagnostic importance of the various mental disturbances which may be encountered early in its course are noted. The acute or subacute course may reflect a widespread mechanical interference with normal cerebral metabolism, a notion which is supported by recent clinical measurements in these patients of the rate of glucose transport across the blood-brain barrier. It is probable that the route taken by tumour cells to reach the meningeal spaces is a relatively unimportant factor in determining this pattern of growth and that the intrinsic growth characteristics of the primary tumour, its nutritional needs, and gravity probably play the major roles in production of this unusual type of secondary invasion. Greater therapeutic use of irradiation for these patients is encouraged. (+info)
ACTINOMYCOSIS OF THE BRAIN; CASE REPORT AND REVIEW OF THE LITERATURE.
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The available world literature (since Friedman's and Levy's comprehensive report in 1937) regarding actinomycosis of the central nervous system is reviewed. Only cases proved by culture were included in this analysis. A total of 17 cases was collected and an additional patient with this entity is described.The important differences between actinomycosis and nocardiosis are discussed. A definite diagnosis of actinomycosis was possible only when anaerobic cultures of cerebrospinal fluid or material obtained from a brain abscess yielded colonies of typical Actinomyces organisms. The characteristic result of infection of the brain by this fungus was abscess formation, and this occurred in all except one of the cases reviewed. Penicillin appears to be the drug of choice in treatment and, where possible, surgical excision of the cerebral abscess should be undertaken. (+info)
Physical and chemical properties of drug molecules governing their diffusion through the spinal meninges.
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Drugs administered into the epidural space for selective spinal analgesia must diffuse through the spinal meninges to gain access to their sites of action in the spinal cord. Therefore, knowledge of the physical and chemical properties of drug molecules that govern their diffusion through the meninges is important for understanding the pharmacokinetics of epidural analgesia. To determine the physicochemical properties of drug molecules that govern the rate at which drugs diffuse through the spinal meninges, the authors measured the permeability coefficient of eight different drug molecules through the spinal meninges of the monkey using a previously established in vitro model. We previously reported permeability measurements for four of the molecules used in this study; the other four molecules' permeability measurements are new. The measured permeability coefficient was then correlated with the drugs' molecular weight, molecular surface area, molecular volume, length of the major molecular axis, and octanol:buffer distribution coefficient. We found no relationship between the drugs' permeability coefficients and any measure of drug mass, molecular shape, or molecular size. There was, however, a biphasic relationship between the octanol: buffer distribution coefficient and the drugs' measured permeability coefficients. Drugs that were either very hydrophilic or very hydrophobic had permeability coefficients that were significantly less than drugs of intermediate hydrophobicity. These data suggest that it should be possible to design novel analgesics for which meningeal permeability is maximal. (+info)
Anatomy and functionality of leptomeningeal anastomoses: a review.
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BACKGROUND: This review seeks to provide a structured presentation of existing knowledge of leptomeningeal anastomoses from anatomic and functional points of view and to identify problems and possible research directions to foster a better understanding of the subject and of stroke mechanisms. SUMMARY OF REVIEW: Available data show that leptomeningeal anastomoses may be important in understanding stroke mechanisms and that leptomeningeal anastomoses play an important role in penumbra outcome. However, the literature shows no consensus between statements on the existence of leptomeningeal anastomoses and compensatory capacity. CONCLUSIONS: By analyzing the available literature and identifying the factors that contribute to this confusion, we found that variability and the functional consequences thereof are important but that quantitative data are lacking. Moreover, vascular remodeling is an issue to consider. (+info)