Differentiation Of Endogenous Neurogenesis And Secretion Of Neurotrophic Factors In The Focal Cerebral Ischemic Rats

BackgroundThe functions of neurogenesis in pathologic conditions such as ischemia attacks or traumatic brain injuries are not fully understood. Whether the repair of injured long distant neural pathways is by virtue of direct replacement by the axons of newborn neurons or the beneficial effects of the neurotrophic factors secreted is not clarified.ObjectiveWe aimed to certify whether newborn neurons could differentiate into projection neurons to form the long distance pathway and whether they could secrete neurotrophic factors after ischemic injury induced by medial cerebral artery occlusion model in rats.Materials and MethodsThis study was mainly divided into2parts. In the first part, we made a medial cerebral artery occlusion (MCAO) model while the regional cerebral blow flow (rCBF) was monitored by a Doppler instrument to induce ischemic injury in adult rats. We used methods of double immunofluorescence labeling and retrograde tracing techniques to identify newly formed neurons. In the second part, we used methods of enzyme-linked immunosorbent assay (ELISA)and partial quantitive reverse transcript polymerase chain reaction (RT-PCR) to observe the secretion of three neurotrophic factors, including nerve growth factor (NGF),brain-derived neurotrophic factor (BDNF) and Neurotrophin-3(NT-3).ResultsIn part1, we found focal ischemic injury could induce neurogenesis, especially in the subventricular zone (SVZ) and dentate gyrus (DG) of hippocampus. Newborn cells blasted on the1st week after MACO, then decreased. Newborn cells could immigrate into the penumbra zone near the infarct area.Newborn cells could differentiate into calbindin-positive interneurons, but not N200positive projection cells.And retrograde tracing technique also provedthat he damaged long distance pathway could not be reconstructed via the replacement of newborn neurons.In part2, ELISA results revealed the secretion of neurotrophic factors promoted after ischemic injury.And the secretion synchronized with the neurogenesis. The concentrations of three target neurotrophic factors in the cerebrospinal fluid (CSF) were at peak on the1st week after ischemia. Then they dropped down.But BDNF re-climbed to another peak on4th week. And RT-PCR showed that the transcriptions of three target factors different in different locations and time after ischemia. Conclusion Thus, our results diminished the possibility that the recovery of the neural function impaired by the ischemia injury was due to the replacement of the damaged projection tracts but to the local circuit's plasticity, and suggested the potentially special effects of neurotrophic factors in post ischemia neural repair.