Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice.
Peripheral stimulation and physical therapy can promote neurovascular plasticity and functional recovery after CNS disorders such as ischemic stroke. Using a rodent model of whisker-barrel cortex stroke, we have previously demonstrated that whisker activity promotes angiogenesis in the penumbra of the ischemic barrel cortex. This study explored the potential of increased peripheral activity to promote neurogenesis and neural progenitor migration toward the ischemic barrel cortex. Three days after focal barrel cortex ischemia in adult mice, whiskers were manually stimulated (15 min x 3 times/day) to enhance afferent signals to the ischemic barrel cortex. 5-Bromo-2'-deoxyuridine (BrdU, i.p.) was administered once daily to label newborn cells. At 14 days after stroke, whisker stimulation significantly increased vascular endothelial growth factor and stromal-derived factor-1 expression in the penumbra. The whisker stimulation animals showed increased doublecortin (DCX) positive and DCX/BrdU-positive cells in the ipsilateral corpus of the white matter but no increase in BrdU-positive cells in the subventricular zone, suggesting a selective effect on neuroblast migration. Neurogenesis indicated by neuronal nuclear protein and BrdU double staining was also enhanced by whisker stimulation in the penumbra at 30 days after stroke. Local cerebral blood flow was better recovered in mice that received whisker stimulation. It is suggested that the enriched microenvironment created by specific peripheral stimulation increases regenerative responses in the postischemic brain and may benefit long-term functional recovery from ischemic stroke.
Li
Wen-Lei
WL
Department of Neurology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Yu
Shan Ping
SP
Ogle
Molly E
ME
Ding
Xin Sheng
XS
Wei
Ling
L
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000503:physiopathology*; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology; D007511:Ischemia / Q000473:pathology / Q000534:rehabilitation*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods*; D011897:Random Allocation; D012039:Regional Blood Flow; D013997:Time Factors; D014738:Vibrissae / Q000294:innervation*
C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D001973:Bromodeoxyuridine
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