Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury.
Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37 °C); sham injury with hypothermia group (32 °C); TBI with normothermia group (TNG; 37 °C); and TBI with hypothermia group (THG; 32 °C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32 °C) was achieved by partial immersion in a water bath (0 °C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90 ± 2.36% in TNG and 14.90 ± 1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia.
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Yichao
Y
Jin
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Yingying
Y
Lin
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Jun-feng
JF
Feng
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Feng
F
Jia
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Guo-yi
GY
Gao
Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University , School of Medicine, Shanghai, China .
Ji-yao
JY
Jiang
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D001831:Body Temperature / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007036:Hypothermia, Induced; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins
autophagy; cell death; hippocampus; moderate hypothermia; traumatic brain injury