Intraventricular Injection Of Basic Fibroblast Growth Factor In Rats With Traumatic Brain Injury

The incidence of traumatic brain injury (TBI) increased continuously with the development of economy, science and technology. And the mortality and mutilation of TBI was the highest in organ damage. Currently, neurotrophic drugs and physical therapy, is difficult to achieve satisfactory curative effect. So the problem how to restore the disorders and deficits of nervous functions after TBI always puzzles the neurologists.The discovery and application of neural stem cells (NSCs) provide a novel idea of the central nervous system deficits due to their regenerative ability and the potential to transform into a host of different cells, that is, they could proliferate and differentiate into particular direction under appropriate conditions. Presently, the treatment of nerve system deficits by NSCs falls into two categories: "replacement therapy", to transplant exogenous NSCs; "supplement therapy", to activate endogenous NSCs. But the exogenous NSCs were source-limited and difficult to obtain, and they are also bounded by the immunological rejection after transplantation, medical ethics and law, compared with endogenous NSCs. However, the proliferation and differentiation of endogenous NSCs were not enough to repair the nerve injury, so we could promote and enhance the proliferation and differentiation of endogenous NSCs to achieve a better effect.Basic fibroblast growth factor (bFGF) is a kind of mitogens with strong bioactivity, which is related to embryonic development and stability of the adult tissues. It could promote the formation of blood vessels, improve microcirculation and promote the regeneration of injured nerves, blood vessels, and skin, etc. BFGF is a broad-spectrum neurotrophic factor which could repair, protect the injured nerve cells and promote the recovery of neural function.This study aims to observe the proliferation of endogenous NSCs, evaluate the recovery of limb function, and analyze the relationship between them by experimental intraventricular injection of bFGF to the rats with TBI, providing the experimental basis for the "supplement therapy" of TBI.Objective To investigate the effect of basic fibriblast growth factor (bFGF) by intraventricular injection in rats with traumatic brain injury (TBI), which may provide experimental basis for the treatment of TBI by the activation of endogenous NSCs.Methods Twenty-four adult SD rats were randomly divided into 2 groups, the treatment group and the control group, each of 12 rats. Model of traumatic brain injury was established by freely falling body hit of improved Feeney's method. And 24 h after TBI, intraventricular injection of bFGF was performed in rats of the treatment group and isometric physiological saline in rats of the control group. The restoration of limb function was observed by behavior test (forelimb placing test and beam balance test) grading. From 1 d to 14 d after TBI, the behavior of rats was evaluated in the same period until they were executed. Expression of BrdU-positive cells labeled by proliferating endogenous neural stem cells with bromodeoxyuridine (BrdU) in the lateral subventricular zone (SVZ), the dentate gyrus of the hippocampus and the injured regions at 3 d, 7 d, 14 d after TBI in two groups was observed with immunohistochemical staining.Results After the injury, the abduction of limbs on the opposite side was affected and hypomyotonia and gait with turning to or dumping on the opposite side occurred in two groups. There was significant difference between two groups in the grading of forelimb placing test and beam balance test (P≤0.05): in the forelimb placing test, significant statistical difference was found from 3 d to 12 d (P≤0.05); in the beam balance test, significant statistical difference was found from 3 to 11 d (P≤0.05). Compare with the control group, BrdU-positive cells in the bilateral SVZ, the dentate gyrus of the hippocampus and injured regions were increased significantly in treatment group (P≤0.05). The number of BrdU-positive cells on the injured side was significantly higher than that on the opposite side (P≤0.05). The grading of behavior test was negatively correlated with the number of BrdU-positive cells.Conclusions Intraventricular injection of bFGF can improve the proliferation of endogenous neural stem cells and the recovery of limbs function in the rats with TBI.