title: 5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.
abstract: Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Yi-Feng
authors: YF
authors: Miao
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Hui
authors: H
authors: Wu
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Shao-Feng
authors: SF
authors: Yang
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Jiong
authors: J
authors: Dai
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Yong-Ming
authors: YM
authors: Qiu
authors: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX 77096, USA.
authors: Zhen-Yi
authors: ZY
authors: Tao
authors: Department of Neurosurgery, Ren Ji Hospital, South Campus, Shanghai Jiao Tong University School of Medicine, Shanghai 201112, China.
authors: Xiao-Hua
authors: XH
authors: Zhang
mesh_terms: D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007036:Hypothermia, Induced; D007249:Inflammation / Q000517:prevention & control*; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051193:Toll-Like Receptors; D000249:Adenosine Monophosphate; D019272:Leukocyte Elastase