Abstract:

BACKGROUND: Neural stem cells (NSCs) have the potential of self-proliferation and multiple directional differentiation, and can differentiate into various cells in the neural system under a certain condition. Therefore, NSCs have good prospect in repair of nerve injury. However, RNA interference avoids the abuse of permanent gene silencing, and is hopeful to combine with NSC transplantation for treating craniocerebral injury.
OBJECTIVE: To determine whether the Nogo-66 receptor (NgR) gene silencing in NSCs can enhance curative effects of stereotaxic intracerebral transplantation of NSCs on traumatic brain injury (TBI) in rats.
METHODS: A total of 60 male Wistar rats following TBI establishment were randomly assigned to 3 groups (n = 20). In the experimental group, NgR gene silencing NSC suspension (6 μL) was injected into rat brain tissue following 24 hours of model induction. In the control group, an equal volume of NSC suspension was infused by the same method. In the blank group, an equal volume of medium without stem cells was infused by the same method. At 24 hours, 3 days, 1 and 2 weeks following injury, neurological deficits were scored. Two weeks later, animals were sacrificed and subjected to immunohistochemistry and hematoxylin-eosin staining.
RESULTS AND CONCLUSION: Following transfection of small interfering RNA, compared with control group, NgR gene protein expression was significantly reduced in the experimental group. At 1 and 2 weeks following transplantation, neurological deficit score was significantly less in animals undergoing NSC transplantation in the experimental group compared with the control group (P < 0.05). Moreover, neuron number in the brain tissue sections of experimental group was significantly more than in the control group (P < 0.01). At 2 weeks following injury, hematoxylin-eosin staining showed that brain tissue breakage at damaged site as scar connection, remarkable porosis in the blank group; typical morphological changes as neural cells at the transplanted site in the control group; typical morphological changes as neural cells without cavity in the experimental group. Immunohistochemistry showed (37.92±16.02) BrdU-labeled positive cells/high-power field in the blank group, (89.68±15.34) cells/high-power field in the control group, and (102.67±13.52) cells/high-power field in the experimental group. Significant differences were detected between groups (P < 0.01). The above-mentioned results indicated that the NSCs of NgR gene silencing transplanted into the injured cerebral tissues can significantly improve the neurological function in rats with TBI.