title: Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events.
abstract: BACKGROUND
  Diabetes and cerebral ischemic-reperfusion are among the most common causes of neurological complications in Egypt. The prevalence of diabetes in Egypt is high and it can be considered as a major clinical and public health problem.
  
  
  METHODS
  Blood glucose, lipid profile, oxidative stress makers (cerebral MDA & GSH), cerebral interleukin-4 (IL-4) level and cerebral cyclooxygenase-2 (COX-2) gene expression were measured in male albino rats weighing 200 ± 20 g. The rats were divided into five groups, normal control group, diabetic group (diabetes was induced by single dose of streptozotocin [STZ]), diabetic cerebral ischemic-reperfused group, two treated groups (diabetic and diabetic ischemic-reperfused), both groups treated with resveratrol. Histological study was done using H&E, AgNOR and cresyl violet stains. Immunohistochemistry for Bax and COX-2 was done with morphometric study.
  
  
  RESULTS
  Diabetic and diabetic cerebral ischemic- reperfused rats showed significant increase in serum glucose level, serum TAG, serum LDL-C, atherogenic index, cerebral MDA and upregulation of COX-2 gene expression. These groups showed significant decrease in serum HDL, cerebral IL-4 and depletion of cerebral GSH when compared to normal control rats. Treating these groups with resveratrol resulted in significant decrease in serum glucose level, serum TAG, TC, serum LDL-C, atherogenic index, cerebral MDA and downregulation of COX-2 gene expression. The results of COX-2 gene expression were confirmed by COX-2 immunohistochemistry. Also, significant increase in serum HDL, cerebral IL-4 and cerebral GSH contents could be observed in these treated groups as compared to normal control group. Cerebral apoptotic index and optical density of Bax reaction revealed significant increase in diabetic and diabetic cerebral ischemic-reperfused rats while treatment of these groups with resveratrol resulted in significant decrease in cerebral apoptotic index and optical density of Bax reaction. These apoptotic results were confirmed with AgNOR and cresyl violet stains.
  
  
  CONCLUSIONS
  The results of this research suggest that upregulation of cerebral COX-2 gene along with the decrease in cerebral IL-4 and enhanced cerebral apoptosis is critically involved in cerebral damage associated with diabetes and cerebral ischemic-reperfusion. Resveratrol can ameliorate these effects and has promising neuroprotective effect in diabetic-induced cerebral complications.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Hoda E
authors.initials: HE
authors.lastname: Mohamed
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Sahar E
authors.initials: SE
authors.lastname: El-Swefy
authors.affiliation: Department of Histology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Rehab A
authors.initials: RA
authors.lastname: Hasan
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Hasan
keywords: COX2; Diabetes; Ischemic-reperfusion; Resveratrol and apoptosis