Focal cerebral ischemia activates neurovascular restorative dynamics in mouse brain.
Cerebral ischemia triggers regeneration of neural stem/progenitor cells (NSCs/NPCs), which are associated with neovascularization and white matter repair in the brain. This study analyzed the dynamics of neurogenesis, neovascularization, and white matter injury/repair after middle cerebral artery occlusion (MCAO) and elucidated their temporal association. Mice were subjected to MCAO for 60 minutes and sacrificed up to 28 days after reperfusion. Neurogenesis and angiogenesis, as measured by double staining of 5-bromo-2-deoxyuridine (BrdU) with DCX or tomato lectin, respectively, were substantially activated soon after ischemia and persisted for 4 weeks. Despite the moderate recovery of functional vessels in infarct margin from 7 days post-ischemia, a significant decrease in vascular density remained over time. Clusters of immature neurons localized proximal to angiogenic blood vessels beginning 14 days after ischemia, suggesting interplay between neurogenesis and revascularization. Progenitors of oligodendrocytes (NG2+) constitutively presented in the normal brain and proliferated soon after ischemia. However, axon damage and the loss of white matter integrity after ischemic stroke were almost irreversible, as revealed by sustained decreases of myelin basic protein (MBP) and neurofilament-200 expression.
State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Min
M
Chu
Xiaoming
X
Hu
Shiduo
S
Lu
Yu
Y
Gan
Peiying
P
Li
Yanling
Y
Guo
Jia
J
Zhang
Jun
J
Chen
Yanqin
Y
Gao
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL