The ER chaperone GRP78 with antiapoptotic properties is a central regulator of ER homeostasis, and its up-regulation is widely used as a sentinel marker for ER stress under pathologic conditions. As a major ER chaperone, GRP78 facilitates protein folding, preventing intermediates from aggregating and promoting misfolded protein for proteasome degradation. Our result has revealed the activation of GRP78 started at 6 h after ischemia and reached the peak at 24 h after ischemia attack. Compared with the ischemia group, the amount of GRP78 expression in hypothermia group is much more than that in ischemia group which is in. consistent with the finding of Masayuki Aoki. There was a significant reduction in the number of TUNEL-positive cells in the hippocampus CA1 in the hypothermia group rats at 48 h of reperfusion in our study. Therefore, we believe that the increased GRP78 expression contributes to the hypothermia-induced neuroprotection in hippocampus area against cerebral ischemia.A similar result can also be obtained for IDE secretion, by using an ELISA assay on BV-2 cell supernatants collected 24 hrs after the administration. Notably, IDE is the main extracellular protease secreted by microglia involved in Ab degradation, even though the molecular basis of IDE regulation are poorly known. Secondly, as the disease progresses, the microglia Abclearing capability is compromised. This downregulation is followed by an increase of Ab released by neurons and by a worsening of the disease. We previously demonstrated that sst is an allosteric modulator of IDE. In this work, we further study the effect of sst on IDE showing that the neuropeptide somatostatin also specifically regulates IDE, the main extracellular Ab protease, by affecting its expression and secretion in both primary and BV-2 microglia cells. Somatostatin triggers IDE gene transcription and protein which displays a different turnover rate: IDE-mRNA reaches a maximum of transcription within 5 hrs after stimulation, returning to the basal level within 24 hrs, whereas the protein concentration increases in cell lysates and supernatants at later times, being still clearly evident after 24 hrs. Through this pathway, somatostatin enhances IDE secretion, strengthening the pool of active enzymes which interact with bamyloid and other IDE extracellular substrates. This effect is specific for IDE since sst does not affect either secretion and activity of MMP-9, another enzyme which is active in Ab degradation. It is known that IDE and somatostatin levels are altered in AD progression. It is thus conceivable that sst depletion results in a decrease of IDE expression and secretion contributing to the pathological deposition of b-amyloid in the brain.This generates the hypothesis that the reduced ability to deal with low temperatures in low- latitude populations which improves survival at low temperatures.