The pathophysiological mechanism of ischemic stroke after hypobaric hypoxia simulation at high altitude.

Abstract

Tibet is an area in China with a high incidence of stroke, typically attributed to hypobaric hypoxia. The present study aimed to observe the neuronal injury of ischemic stroke after hypobaric hypoxia and explore the mechanism by which N-methyl-D-aspartate receptor (NMDAR) and its downstream pathways are involved. This study employed a hypobaric chamber to imitate high altitude at 4000m. After hypoxia, the middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke. Behavioral tests and measurements of infarct area were used to observe neuronal injuries. The expression of NMDAR, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII (Threonine 286) (P-CaMKII) was tested by western blot, and hematological tests were used to count the number of red blood cells (RBCs) and hemoglobin. Compared with the plain+MCAO group, the neurological deficit scores and infarct area of rats in the 4000m + MCAO group were all decreased, and the protein expression of NMDAR, CaMKII and P-CaMKII was reduced. Compared with the plain group, the numbers of RBCs, hemoglobin and hematocrit were increased in the 4000m group; compared with the 4000m groups, the three indexes were increased in the 4000m + MCAO groups. The neuronal injuries after hypoxia were not more serious than those in rats enduring ischemia and reperfusion in plain. The underlying mechanisms were related to the decreased expression of NMDAR and CaMKII; furthermore, the increased numbers of RBCs and hemoglobin may be crucial mechanisms for the incidence and development of ischemic stroke at high altitude.