Na～+,K～+-TPaseα Isoform Involves In Ischemic Cerebral Injury

Cerebral ischemia is always followed by low energy metabolism, high level of free radical and excitatory amino acids, overload of intracellular Ca2+, and destruction of cell structure. It is believed that the failure of energy metabolism in brain cells is the main driving factor of neural damage. After cerebral ischemia aerobic metabolism is converted to anaerobic metabolism and the production of ATP in the ischemic cells is only as much as 1/18 in the non-ischemic cells. The activity of Na+,K+-ATPase in the cell membrane is decreased because of the ATP exhaustion, resulting in a increase of extracellular K+ concentration, and a sudden decrease of intracellular Na+,Cl- concentrations. H2O moves into cells by osmotic gradient from the interstitial tissue and causes cytotoxic edema.Na+,K+-ATPase in brain tissue exists on the synaptic membrane (SPM) and microvascular endotheliocyte (CMV). In the early stage of brain ischemia, Na+,K+-ATPase activity is increased in CMV and decreased in SPM. The change of Na+,K+-ATPase activity results in the movement of Na+ from extra-cell space to intra-cell and cause cellular edema. In the later stage Na+,K+-ATPase activity is decreased both in CMV and SPM,and brain edema is deteriorated. The evidence suggests that changes of Na+ ,K+-ATPase activity may participate in the occurrence and development of brain edema.In addition to causing edema, cerebral ischemia always induces the depolarization of cell membrane and a lot of presynaptica excitatory transmitter is released, which, together with insufficient intracellular ATP, lactate acidosis, and reduction of Na+,K+-ATPase activity, raises intracellular Na+ concentration. As a result, overload of intracellular Ca2+ occur through the inverse mode of Na+-Ca2+ exchange. The activation Ca2+-related phosphatidase, protease, endonuclease induces decomposition of membrane phospholipid and...