Background and Purpose: Vascular dysfunction and resultant chronic cerebral hypoperfusion leads to VCI, the second most common cause of dementia. We reported that RIC-therapy improves cerebral blood flow (CBF) in both murine stroke and VCI models. In the present work, we hypothesized that long-term RIC-therapy after VCI will promote neurovascular plasticity via up-regulation of growth factors.
Methods: Microcoil induced bilateral common carotid artery (BCAS) model was used to induce chronic hypoperfusion. Adult C57BL/6J male mice of (10-weeks) were assigned to 3-different groups (N=6), and subjected to Sham- (procedures of BCAS and RIC), BCAS- (induced VCI followed by RIC-Sham), and BCAS+RIC (induced VCI followed by RIC-therapy). RIC was started 7d post-surgery for 2-wks. At 4-wks post-surgery (1-wk after the cessation of RIC) CBF was determined using laser speckle contrast imager (LSCI). Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire test for motor impairment. Histopathology as well as immunohistochemistry for BDNF and VGEF were also performed on the of the brain tissue collected after the neurobehavioral tests. Statistical significance was determined at p <0.05.
Results: RIC-therapy significantly improved CBF in BCAS+RIC group compared to the BCAS group. Mice from the BCAS group showed significant loss in the discrimination index as determined by the NOR test, and poor motor function strength in hanging wire test. RIC-therapy in BCAS+RIC group significantly improved functional outcomes as compared to the BCAS-group. Histopathological studies clearly showed prevention of neurovascular degeneration by RIC. Interestingly, immunohistochemical analysis revealed loss in BDNF and VEGF expressions in the BCAS-group as compared to Sham that was increased in the BCAS+RIC-group.
Conclusions: RIC-therapy attenuates neurovascular stress via improved CBF that attenuates neurovascular degeneration and prevents functional impairments. RIC increases BDNF and VEGF levels. Long term RIC-therapy could be a conventional therapy for aged individuals suffering from VCI and resultant motor impairment.