Phenytoin pretreatment prevents hypoxic-ischemic brain damage in neonatal rats
| Autor: | Charles Taylor, Kadee J. Raser, Avigail Posner, John J. Cordon, Kevin K.W. Wang, Nancy C. Kupina, Gerald P. Schielke, Mark G. Vartanian |
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| Rok vydání: | 1996 |
| Předmět: |
Phenytoin
medicine.medical_specialty medicine.medical_treatment Ischemia Brain damage Neuroprotection Brain Ischemia Rats Sprague-Dawley Brain ischemia Developmental Neuroscience Internal medicine medicine Animals Hypoxia Brain Dose-Response Relationship Drug biology business.industry Spectrin Calpain Hypoxia (medical) medicine.disease Rats Neuroprotective Agents Endocrinology Anticonvulsant Animals Newborn Anesthesia biology.protein Anticonvulsants Brain Damage Chronic medicine.symptom business Body Temperature Regulation Developmental Biology medicine.drug |
| Zdroj: | Developmental Brain Research. 95:169-175 |
| ISSN: | 0165-3806 |
| Popis: | This study was performed to investigate whether the anticonvulsant phenytoin has neuroprotective effect in a model of hypoxia-ischemia with neonatal rats. The left carotid artery of each rat was ligated, followed by 3 h of hypoxic exposure (8% O2) in a temperature-regulated environment (36 degrees C). Two weeks later, brain damage was assessed by measuring loss of brain hemisphere weight. Phenytoin had no effect on body temperature or plasma glucose, but attenuated brain damage in a dose-dependent manner (3, 10, and 30 mg/kg i.p.) when administered before the hypoxic episode. Phenytoin administered during or after hypoxia did not alter hypoxic brain damage significantly. A parallel experiment using histological examination of frozen brain sections demonstrated less brain infarction after phenytoin treatment (30 mg/kg i.p.). In an additional experiment measuring breakdown of an endogenous brain calpain substrate, spectrin, phenytoin treatment reduced this measure of early cellular damage. Our results indicate that pretreatment with phenytoin is neuroprotective at a plasma phenytoin concentration of approximately 12 micrograms/ml. These results are consistent with the hypothesis that blockade of voltage-dependent sodium channels reduces brain damage following ischemia. |
| Databáze: | OpenAIRE |
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