Spatial Changes Of Blood Flow, NMDA Receptor, M Receptor And NO During Focal Cerebral Ischemia/Reperfusion In The Rat

Background and purpose: The process of brain damage during focal cerebral ischemia is very complex and is influenced by many factors, among which the changes of cerebral blood flow (CBF), receptors and NO are the three key responsible factors. Since middle cerebral artery occlusion (MCAO) is most frequently involved in focal cerebral ischemia, the model of MCAO is the standard model to study brain ischemia. Receptor imaging is an important direction in the nuclear medicine research, especially in the development of positron emission tomography (PET). Some receptor imaging has already been applied to the diagnosis of brain diseases. Reperfusion often appears after clinical thrombolysis in the cerebral ischemia and thus influencs the progress of ischemia by counteracting the changes resulting from ischemia.In this study, the intraluminal suture method was used to produce a cerebral ischemia/reperfusion model. The relationship between the changes of CBF and histology, the changes of NMDA receptor, M receptor and NO during cerebral ischemia/reperfusion were studied. The aims were to accumulate data which might be used in the diagnosis, therapy and recovery of brain ischemia, perhapes also in the study of other brain diseases with changes of the brain function. Methods: Wistar rats, male/female, weighing from 250 to 300 grams, were used. (1) The rat MCAO ischemia/reperfusion model was made by the intraluminal suture method. (2) In the study of focal cerebral ischemia/reperfusion jury, the frozen brain slices were stained by crestyl violet to observe the pathological changes in different areas. Zea longa criterion was used to grade the behavior of the experimental animal and brain edema was detected by the brain H₂O content. The animals were divided into nine groups: Sham group, 2 hours' occlusion (O2), 24 hours' occlusion (O24), 2 hours' reperfusion after 2 hours' occlusion (O2R2), 4 hours' reperfusion after 2 hours' occlusion (O2R4), 8 hours' reperfusion after 2 hours' occlusion (O2R8), 24 hours' reperfusion after 2 hours' occlusion (O2R24), 72 hours' reperfusion after 2 hours' occlusion (O2R72), 24 hours' reperfusion after 4 hours' occlusion(O4R24). (3) In the study of CBF and histology during focal cerebral ischemia/reperfusion, ^99mTc-HMPAO was used as an imaging agent and scanned under BI screen, using of CS-250 molecular imaging system. Autoradiography was used to study the changes of CBF, areas and histology in different locations. Eight groups of animals were compared: Sham group, 5 minutes' occlusion (O5m), 2 hours' occlusion (O2), 2 hours' occlusion (O4), 15 minutes' reperfusion after 2 hours' occlusion (O2R15m), 2 hours' reperfusion after 2 hours' occlusion (O2R2), 4 hours' reperfusion after 2 hours' occlusion (O2R4), 24 hours' reperfusion after 2 hours' occlusion (O2R24).