Abstract W P90: Valproic Acid Ameliorates Ischemic Brain Injury in Hyperglycemic Rats with Permanent Middle Cerebral Occlusion
Background: Valproic acid (VPA) is widely used for the treatment of epilepsy in clinic. Some previous studies demonstrated that VPA ameliorated brain injury following experimental stroke. However, the effect of VPA in stroke model with comorbid conditions has not been fully studied. In this study, we investigated the effects of VPA in permanent ischemic stroke with hyperglycemia.
Methods: Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion according to a modification of the Tamura method. Hyperglycemia was induced by streptozotocin (STZ) injection 3 days before ischemia induction. The animals received a single injection of VPA immediately after the induction of ischemia. Vehicle-treated animals underwent the same procedure with physiological saline. Infarct volume, neurological deficits and immunohistological assessments were performed 3 days after ischemia.
Results: Hyperglycemia significantly enhanced the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and neurological deficit compared with normoglycemia (p < 0.05; Figure). VPA significantly alleviated the aggravation of neurological deficit by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (p < 0.05; Figure).
Conclusions: Our results showed that VPA ameliorated neurological deficits through modulating the inflammatory responses and protecting endothelial damage, leading to reduced neuronal cell death following ischemia in STZ-induced hyperglycemic rats.
Author Disclosures: S. Suda: None. M. Saito: None. T. Inaba: None. Y. Nishiyama: None. C. Nito: None. M. Ueda: None. Y. Katayama: None. K. Kimura: None.
- © 2015 by American Heart Association, Inc.