Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake.

摘要: The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 μmol (1 M) the succinate dehydrogenase inhibitor malonate. VPA-treated animals developed smaller lesions than control animals: 10 ± 2 mm3 versus 26 8 (means SD; P = 10−4). Injection NaCl that was equiosmolar 1 M malonate caused only 1.2 0.4 in animals, whereas physiologic saline produced no lesion. pretreatment reduced malonate-induced extracellular accumulation glutamate. This effect paralleled an increase striatal level glutamate transporter GLT, which augmented high-affinity uptake by 25%, as determined from [3H] into proteoliposomes. Malonate a 76% reduction adenosine triphosphate (ATP) content, but glial, ATP-dependent formation glutamine radiolabeled glucose or intact, indicating g...