The HBO promotes neural progenitor cells migration via endothelial nitric oxide synthase regulating SDF-1/CXCR4 in transient brain ischemia

• Main Authors: I-Ling Lu, 呂怡陵
• Other Authors: Ray-Yau Wang
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/54648812772214893727

碩士 === 國立陽明大學 === 物理治療暨輔助科技學系 === 100 === Background: Neurogenesis is found surrounding the peri-infarct region and contributes to functional recovery after stroke. The hyperbaric oxygenation (HBO) has been noted to be beneficial after brain ischemia, however, its effects on neural progenitor cells (NPCs) is still unknown. This study aimed to investigate multiple HBO on NPCs migration via endothelial nitric oxide synthase (eNOS) regulating SDF1/CXCR4 and functional recovery after brain ischemia. Methods: Brain ischemia was induced by middle cerebral artery occlusion (MCAO). Twenty-four male Sprague-Dawley (SD) rats were randomly allocated to the MCAO and HBO+MCAO group with two subgroups (7 and, 28 days) in each group. The HBO was administered with 100% oxygen at 3 ATA for 1 hour each day for 7 days starting from 3 hours post brain ischemia. Rats in the MCAO group received room air as a control. The outcome measures included the migration distance of NPCs as indicated by the immature neural marker-Doublecortin (Dcx) expressed as Brdu+Dcx + /Brdu+%, and functional recovery as indicated by the duration on the Rotarod. The intensity of SDF-1 was measured in the distribution of peri-infarct cortex, and the intensity of eNOS and CXCR4, the number of CXCR4 + with Dcx+ cells were measured from subventricular zone (SVZ) to peri-infarct cortex. The two-way repeated measures of ANOVA was used to compare the results of Rota-rod test and the Bonferroni test were used as the post hoc test. The independent t test was used for other outcome measures to compare the difference between groups. Significance was set at p＜0.05. Results: Rats in the HBO+MCAO group demonstrated significant improvement in the duration on Rota-rod as compared with the MCAO group (day 7 (d7): p<0.05; day 28 (d28): p<0.05). The increase in the proportion of Brdu+Dcx+/Brdu+% in SVZ from 400 μm to 700μm toward peri-infarct cortex was noted at d28 in HBO+MCAO group as compared with its control group (p<0.05). The SDF-1 intensity was significantly increased in d7 in the MCAO+HBO group as compared with its control group (p< 0.05) and the intensity of CXCR4 significantly increased in as compared with MCAO groups at d28. (p<0.05) The number of CXCR4+/Dcx+ cells was increased in the HBO+ MCAO group at distance from 500μm to 700μm measured at d28 (p<0.05). Significant differences in the intensity of eNOS in HBO+MCAO groups were noted as compared with their comparable control groups (d7: p<0.05; d28: p<0.05). Conclusions: HBO not only promoted NPCs migration but also improved functional recovery. The enhanced NPCs migration may be mediated by eNOS via chemotaxis of SDF-1 and CXCR4 interaction.