Affiliations: Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China | Department of Neurological Surgery, University of California, San Francisco, CA, USA | School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
Note: [] These authors contributed equally to this work.
Note: [] These authors contributed equally to this work.
Note: [] Corresponding author: Jian-min Zhang, Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, PR China. Tel.: +86 13805722695; Fax: +86 0571 87784716; E-mails: neurosurgeryzjm@hotmail.com; sunchongran@gmail.com (C.-r. Sun); cae-czh@126.com (Z.-h. Chen); cecile.yin@gmail.com (S.-y. Yin); saintchan@sina.com (S. Chen); neurosurgeryzjm@hotmail.com (J.-m. Zhang).
Abstract: Purpose: How injured long-distance neural tracts are reestablished following ischemic brain injury remains unclear. Theories surrounding reconnection include the growth of newly formed axons from newborn neurons, modification of local circuits and a beneficial influence from neurotrophic factors. This research aimed to find the developing new born neurons and the neurotrophic factors they secreted in a middle cerebral artery occlusion (MCAO) rat model to explain the roles of neural progenitor cells in post-ischemic neurogenesis. Methods: Fifty-three male Sprague-Dawley rats underwent the MCAO procedure or sham operation. Double labeling of specific neuron markers (calbindin and N-200) and a dividing cell marker (BrdU) were used to identify newly formed neurons. Neurotrophic factors were examined in the cerebrospinal fluid in post-ischemic rats using enzyme-linked immunosorbent assay. Results: Ischemic injury induced activation of neurogenesis. The newborn neurons differentiated into calbindin-positive interneurons, but not N-200 positive projection neurons. The concentration of neurotrophic factors was elevated and was in accordance with the neurogenesis seen in ischemic animal models. Conclusion: Our research indicates that the recovery of neural function is not ascribed to the reestablishment of damaged projection tracts, but to the modulation of local circuits and beneficial effects of neurotrophins produced by neural progenitor cells.
