NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat
| Autor: | Mariella Caffo, Gerardo Caruso, Antonino Germanò, Kevin K.W. Wang, Francesca Antonia Arcadi, Jennifer K. Newcomb-Fernandez, Chiara Costa, Filippo Flavio Angileri, Ronald L. Hayes, Francesco Meli, Placido Bramanti, Jose A. Pineda, Stephen B. Lewis |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Excitotoxicity Phenylcarbamates Behavioral deficits medicine.disease_cause Cisterna magna Blood–brain barrier Neuroprotection Receptors N-Methyl-D-Aspartate Felbamate Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals Blood-Brain Barrier Rats Subarachnoid Hemorrhage Evans Blue Cognitive deficits NMDA receptor Postural Balance Behavior Animal Dose-Response Relationship Drug business.industry Microcirculation Body Weight Glutamate receptor Endocrinology medicine.anatomical_structure Neuroprotective Agents Spectrometry Fluorescence chemistry Propylene Glycols Anesthesia Cerebrovascular Circulation Neurology (clinical) business medicine.drug |
| Zdroj: | Journal of neurotrauma. 24(4) |
| ISSN: | 0897-7151 |
| Popis: | Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectrophotofluorimetric technique 2 days post-injury). Animals were injected with 400 muL of autologous blood into the cisterna magna. Within 5 min, rats received daily oral administration of FBM (15, 30, or 45 mg/kg) for 2 or 5 days. Results were compared with sham-injured controls treated with oral saline or FBM (15, 30, or 45 mg/kg). FBM administration significantly ameliorated SAH-related changes in Beam Balance scores on days 1 and 2 and Beam Balance time on days 1-3, Beam Walking performance on days 1 and 2, and Body Weight on days 3-5. FBM also decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This study demonstrates that, in terms of behavioral and microvascular effects, FBM is beneficial in a dose-dependent manner after experimental SAH in rats. These results reinforce the concept that NMDA excitotoxicity is involved in the cerebral dysfunction that follows SAH. |
| Databáze: | OpenAIRE |
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