The Effects Of Hyperglycemia On The Hippocampal Ischemic Microenvironment And VEGF Expression In Tree Shrews

Objectives: We observed the effects of hyperglycemia on the hippocampal cell microenvironment and the changes of vascular endothelial growth factor (VEGF) expression after focal cerebral ischemia in tree shrews. So that we can elucidate the action and mechanism of hyperglycemia in ischemic brain damage, and explore the relationship between cerebral ischemia, hyperglycemia and VEGF, and provide the pathophysiologic clues for clarifying the possible mechanisms of secondary neuronal injury and neuronal protection under the conditions of cerebral ischemia and hyperglycemia. Methods: We induced high blood glucose in tree shrews by intraperitoneal injection of streptozotoctin(STZ). Focal cortical thrombotic cerebral ischemia was induced by photochemical technology in tree shrews. At 4, 24 and 72 hours after cerebral ischemia, the changes of pH, K⁺, Na⁺, Ca²⁺ and Cl^- in the ipsilateral ischemic hippocampal microenvironment were tested by a kind of single-pumped push-pull perfusing system and the ion analyzer. And then we examined the histopathological changes with a light microscope to reflect the degree of brain damage. The average grey level of VEGF expression in the cerebral cortex and hippocampus was detected by immunohistochemistry technology at different times after cerebral ischemia under the normoglycemic and hyperglycemic conditions. Results: After focal cerebral cortex ischemia, in the hippocampal microenvironment, pH declined markedly, K⁺ concentration increased, Na⁺, Ca²⁺ and Cl^- concentration decreased. These changes were most noticeable at 4h after occlusion, took second place at 24h, and come back gradually at 72h after occlusion. Hyperglycemia without ischemia didn't induce the marked changes of these parameters. But the combination of hyperglycemia and ischemia made the turbulence of ischemic microenvironment worse. For instance, compared with the normoglycemic stroke animals, the changes were more significant in hyperglycemic animals at the corresponding period, that including pH, K⁺and Ca²⁺ concentration at 4h after occlusion and the contents of pH and Na⁺ at 24h after brain ischemia (P <0.05) . The histopathological study showed...