Activated autophagy pathway in experimental subarachnoid hemorrhage.
Recent results have suggested a role for autophagy in acute brain injury but an involvement in subarachnoid hemorrhage (SAH) has not been investigated. Although, autophagy is a regulated process essential for cellular homeostasis, it may represent an additional type of cell death mechanism. This study employed a modified endovascular perforation rat model under guidance by intracranial pressure monitoring to investigate whether autophagy pathway is involved in the early brain injury following SAH. Sham-operated control rats underwent an identical procedure without vessel perforation. Electron microscopy was performed to examine the ultrastructural changes in neural cells after SAH. Additionally, microtubule-associated protein light chain-3 (LC3), cathepsin-D and beclin-1 were investigated by Western blot analysis and immunohistochemistry. Electron microscopically, there was a marked increase in autophagosomes and autolysosomes in neurons at Day 1 following SAH. Although LC3 could be detected in sham-operated control rats, the conversion of LC3-I to LC3-II was significantly increased at Day 1 (P<0.01) and Day 3 (P<0.05). The time-course of beclin-1 expression paralleled the LC3 conversion. Cathepsin-D expression was also elevated at Day 1 (P<0.01). Immunohistochemical study with antibodies against cathepsin-D and beclin-1 showed numerous positive stained cells after SAH, especially in deep layers of the fronto-basal cortex. Double immunolabeling revealed beclin-1 expression predominantly in neurons. This present study showed that the autophagy pathway is activated in neurons in the acute phase after SAH.
Lee
Jin-Yul
JY
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan, USA. jinyul@umich.edu
He
Yangdong
Y
Sagher
Oren
O
Keep
Richard
R
Hua
Ya
Y
Xi
Guohua
G
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology*