Effects of VEGF combined with BMSC transplantation on neurological function recovery in rats with cerebral hemorrhage: a mechanistic study

Objective To study the effects and mechanism of vascular endothelial growth factor (VEGF) combined with transplantation of bone marrow mesenchymal stem cells (BMSCs) on recovery of neurological function in rats with cerebral hemorrhage. Methods One hundred rats were rando mly divided into 4 groups (n=25 each) . Injection of heparin and collagenase in the right striatum was used to induce cerebral hemorrhage and thereby establish a rat model of cerebral hemorrhage. At 24 h after the injection, the transgene group received injection of exogenous VEGF and transplatation of BMSCs into the right striatum: the BMSCs transplatation group received BMSCs transplantation alone, VEGF group received VEGF injection alone, while the model control group received injection normal saline. mNSS score was assessed at 1, 3, 7, and 14 d after successful modeling. On day 14, the rats were sacrificed and harvested for brain tissues which were subjected to fixation, paraffin embedding and sectioning. The distribution of P75NTR and TrkA in rat brain tissue was detected by immunohistochemistry to evaluate the cell apoptosis. Western Blotting was used to detect the expression levels of P75NTR and TrkA around the hematoma. Results On days 7 and 14, the mNSS score was significantly lower in all treatment groups than that in the control group (6.55±0.95 and 4.65±0.95) , and in the transgene group (3.94±0.73 and 2.24±0.70) than those in the BMSCs group (4.75±0.97 and 3.05±0.88) and VEGF group (5.01±1.01 and 3.34±0.90) . I mmunohistochemistry showed significantly down-regulated P75NTR expression and up-regulated TrkA expression in the brain tissue around the hematoma. Compared with the control group, Western Blotting showed lower expression level of peri-hematoma P75NTR (0.33±0.02, 0.40±0.05 and 0.42±0.04 vs 0.45±0.04) and higher expression level of peri-hematoma TrkA (0.32±0.02, 0.23±0.02 and 0.28±0.04 vs 0.15±0.01) in the transgene group, BMSCs group and VEGF group. These findings in the transgene group were more significantly different from those in the BMSCs group and the VEGF group (P<0.05) . Conclusion VEGF combined with BMSCs transplantation in rats with cerebral hemorrhage may increase TrkA expression and reduce P75NTR expression in the perihematomal cells, inhibit the apoptosis of surrounding cells, and thus promote recovery of neurological function. Key words: Mesenchymal stem cell transplantation; Vascular endothelial growth factor; Cerebral hemorrhage; Apoptosis