Neuronal Repair And Regeneration In Adult Brain After Ischemic Damage

In the present study, brornodeoxyuridine CBrdU) incorporation and nestin expression in adult brain were detected by immunohistochemistry combined with double immunofluorescent labeling techniques to investigate if neuronal regeneration and DNA repair involve in the pathophysiological process following cerebral damage. Adult mice were injected intraperitoneally with BrdU and decapitated at different time points following H-I damage. The increased BrdU incorporation in ipsilateral hemisphere was observed as early as 30 min and the increased expression of nestin immunoreactivity was observed at 4d after H-I damage. Double staining showed that BrdU incorporated into neuron and glia at 2d and incorporated into nest in-positive cells at 4d after H-I damage. In the process of proliferation, BrdU incorporates into DNA synthesis. BrdU incorporation into neuron suggests newly born neuron, but there is also a possibility that BrdU may participate in DNA repair process of damaged neuron after H-I damage. PCNA, a proliferative cell nuclear antigen, is essential for the excision repair of damaged DNA, in addition to DNA replication. All of BrdU co-expressed with PCNA at 2d after H-I damage in present study suggests the role of BrdU may be similar to that of PCNA, TUNEL co-expressed with BrdU verified that BrdU participated in DNA repair process of damage cells. The results suggest that BrdU incorporates into DNA synthesis and repair in vivo, it may participate in DNA repairprocess of damaged cells in the early time following H-I damage. Nestin is a neural stem cell marker. Nestin-positive cells co-expressed with NSE and/or GFAP, which is neuron and astrocyte marker, respectively, were observed in cortex following H-I damage. It suggests that H-I damage initiate a differentiating cascade of neural stem cells, but environmental signal play a key role in regulating the fate of adult stem cell populations in vivo. To observe further nestin expression in adult cerebral brain following ischemia, MCAO model was also used in the present. study. The results showed that nestin-positive cells mapped out the margin of the ischemic core and strongly labeled processes were oriented toward the ischemic core. Double staining also showed that nestin-positive cells co-expressed with GFAP and/or NSE. The results verified that ischemic damage in adult brain induced the expression of nestin and neural stem cells may differentiate into neuron and/or astrocyte after ischemia. On the other hand, previously differentiated neuron and astrocyte may also re-express nestin, which may indicate the recovery and plasticity of neuron and astrocyte. Either neural stem cells differentiation or differentiated cells re-expressing nestin may be favorable for repair and regeneration processes of neuron and astrocyte.