title: Role of autophagy in early brain injury after experimental subarachnoid hemorrhage.
abstract: Autophagy is a self-degradative process and it plays a housekeeping role in removing misfolded or aggregated proteins, clearing damaged organelles, and eliminating intracellular pathogens. Previous studies have demonstrated that autophagy pathway was activated in brain after experimental subarachnoid hemorrhage (SAH); however, the role of autophagy in the pathogenesis of early brain injury (EBI) following SAH remains unknown. Experiment 1 aimed to investigate the time-course of the autophagy in the cortex following SAH. In experiment 2, we chose the maximum time point of autophagy activation and assessed the effects of rapamycin (RAP, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) on regulation of EBI. All SAH animals were subjected to injection of 0.3 ml fresh arterial, nonheparinized blood into prechiasmatic cistern in 20 s. As a result, microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and beclin-1, a Bcl-2-interacting protein required for autophagy, were significantly increased at the early stage of SAH and their expressions peaked at 24 h after SAH. In RAP-treated group, the early brain damage such as brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and clinical behavior scale was significantly ameliorated in comparison with vehicle-treated SAH rats. Conversely, 3-MA decreased expression of LC3 and beclin-1, increased the average value of brain edema and BBB disfunction, and aggravated neurological deficits. Our results suggest that autophagy pathway is activated in the brain after SAH and may play a beneficial role to EBI development.
authors: Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors: Zhong
authors: Z
authors: Wang
authors: Xiao-Yong
authors: XY
authors: Shi
authors: Jia
authors: J
authors: Yin
authors: Gang
authors: G
authors: Zuo
authors: Jian
authors: J
authors: Zhang
authors: Gang
authors: G
authors: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020206:Subarachnoid Hemorrhage, Traumatic / Q000473:pathology* / Q000503:physiopathology