Heat Shock Protein A12B Contributes To Focal Cerebral Ischemia/reperfusion Injury

BackgroundCerebral ischemic injury or ischemic stroke is caused by a deficiency of cerebral blood flew and could result in irreversible brain damage. It is not only the second leading cause of death in the world, but also a leading cause of long-term disability in adults, which has a mortality rate of around 30%. Developing and identifying novel drugs to protect ischemic stroke has become a great issue that we have to face with. Recent evidences have indicated that angiogenic factors such as angiopoietin-1 (Ang1) could protect brain against ischemic injury through stabilization of BBB permeability. Heat shock protein A12B (HSPA12B) is a newly discovered factor that involved in angiogenesis. However, it is still unknown whether overexpression of HSPA12B may attenuate cerebral ischemic injury.SubjectIn the present study, we examined the role of HSPA12B in focal cerebral ischemia/reperfusion injury.MethodsTransgenic mice overexpressing human HSPA12B gene (HSPA12B Tg) were employed in the studies. Cerebral ischemia/reperfusion was induced by middle cerebral artery occlusion (MCAO). The effects of HSPA12B on brain ischemia were then evaluated. 1. Animals:Eight-ten weeks old HSPA12B transgenic mice and WT littermates were employed in the experiments. 2. Evaluation of brain injuries. (1)Infarct size:After ischemia for 60min and reperfusion for 24h, the brain tissues were isolated from mice and subjected to TTC staining. Infarct sizes were then observed and calculated. (2) Neurological scoring: Neurological function was evaluated by using rating scales after the mice were subjected to ischemia 60min/reperfusion 24h. (3) Hippocampal formation injury: After ischemia for 60min and reperfusion for 24h, the brain tissues were isolated from mice and subjected to paraffin section. HE staining was performed. Morphology of hippocampus was then observed under microscope and the images were captured. 3. Blood Brain Barrier permeability:It was expressed as the amount of Evan's blue leaking across BBB after ischemia for 60min and reperfusion for 3h.Results1. Overexpression of HSPA12B decreased the infarct size that induced by MCAO. 2. Overexpression of HSPA12B improved neurological dysfunction that induced by MCAO. 3. Overexpression of HSPA12B attenuated hippocampal formation injury that induced by MCAO. 4. Overexpression of HSPA12B decreased the BBB permeability that induced by MCAO.ConclusionOverexpression of HSPA12B significantly protected mice from MCAO-induced brain ischemic injury.