Abstract
Endoplasmic reticulum (ER) stress has been implicated in the pathology of cerebral ischemia. Apoptotic cell death occurs during prolonged period of stress or when the adaptive response fails. Hypothermia blocked the TNF or Fas-mediated extrinsic apoptosis pathway and the mitochondria pathway of apoptosis, however, whether hypothermia can block endoplasmic reticulum mediated apoptosis is never known. This study aimed to elucidate whether hypothermia attenuates brain cerebral ischemia/reperfusion (I/R) damage by suppressing ER stress-induced apoptosis. A 15 min global cerebral ischemia rat model was used in this study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in hippocampus CA1 were assessed after reperfusion of the brain. The expressions of C/EBP-homolo gous protein (CHOP) and glucose-regulated protein 78 (GRP78) in ischemic hippocampus CA1 were measured at 6, 12, 24 and 48 h after reperfusion. The results showed that hypothermia significantly attenuated brain I/R injury, as shown by reduction in cell apoptosis, CHOP expression, and increase in GRP78 expression. These results suggest that hypothermia could protect brain from I/R injury by suppressing ER stress-induced apoptosis.
Highlights
Hypothermia has been recognized as an effective method in reducing brain injury caused by a variety of neurological insults and may play an important role in emergency brain resuscitation of patients with ischemic stroke, head trauma and cardiac arrest [1,2,3,4,5]
There are no prior studies examining the effects of hypothermia on the Endoplasmic reticulum (ER) stress induced apoptotic pathway after transient global ischemia, so we explored these apoptotic events after transient global ischemia, and investigated the effects of hypothermia hypothermia against transient global ischemia through ER stress pathway in the transient global cerebral ischemia model
3.1 Hippocampus Neuronal Morphology Compared with sham group, the number of normal neurons in hippocampus CA1 area decreased in ischemia and hypothermia group
Summary
Hypothermia has been recognized as an effective method in reducing brain injury caused by a variety of neurological insults and may play an important role in emergency brain resuscitation of patients with ischemic stroke, head trauma and cardiac arrest [1,2,3,4,5]. Hypothermia can reduce the mitochondria pathway of apoptosis which known as intrinsic apoptosis pathway Both the extrinsic and intrinsic apoptosis pathways activate caspases and culminate in neuronal death. ER is the site for protein synthesis and folding, and involved in calcium homeostasis and lipid biosynthesis Many stimuli such as ischemia and hypoxia might perturb ER function resulting in accumulation of unfolded proteins in the ER lumen. Studies have showed chop is the downstream of all three ER stress pathways and plays an important role in endoplasmic reticulum stress [18]. Prolonged ER stress is implicated in the pathogenesis of ischemia and CHOP plays an important role in the cerebral ischemic damage induced by neuronal death. There are no prior studies examining the effects of hypothermia on the ER stress induced apoptotic pathway after transient global ischemia, so we explored these apoptotic events after transient global ischemia, and investigated the effects of hypothermia hypothermia against transient global ischemia through ER stress pathway in the transient global cerebral ischemia model
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