We investigated the probability of newly generated neurons that could survive and mature in the ischemic hippocampal CA1 region (CA1) of a gerbil model of transient cerebral ischemia. Neuronal death was shown in the stratum pyramidale (SP) from 4 days post-ischemia, and a significant increase in NeuN-positive (+) neurons was found in the SP at 180 days post-ischemia. 5-Bromo-2-deoxyuridine (BrdU)+ cells were co-stained with NeuN and glutamic decarboxylase 67 (GAD67). Brain-derived neurotrophic factor (BDNF) immunoreactivity and protein level was shown in nonpyramidal cells from 4 days post-ischemia, and the immunoreactivity was strong at 30 days post-ischemia and not significantly changed until 180 days post-ischemia. Furthermore, TrkB immunoreactivity was co-stained with GAD67 when we examined at 180 days post-ischemia. Myelin basic protein (MBP)+ nerve fibers were reduced at 4 days post-ischemia and maintained until 60 days post-ischemia, and MBP immunoreactivity and levels were significantly increased at 180 days post-ischemia. In the passive avoidance test, cognitive dysfunction was improved at 180 days post-ischemia. These results suggest that the differentiation of neural progenitor cells into new GABAergic neurons may be promoted via BDNF in the ischemic CA1 and that the neurogenesis may partially mediate the recovery of cognitive impairments via increasing myelinated nerve fibers.
Bibliographical noteFunding Information:
The authors would like to thank Mr. Seung Uk Lee for their technical help. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0010580), by the Bio-Synergy Research Project (NRF-2014M3A9C4066454) of the Ministry of Science, ICT and Future Planning through the National Research Foundation, and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (NRF-2013R1A2A2A01068190).
© 2015 International Society of Neuropathology
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Clinical Neurology