Acupuncture improves motor control by up-regulating expressions of BDNF and synaptic proteins in the striatum of neonatal rats with hypoxic-ischemic brain injury

To observe the effect of acupuncture on the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate (cAMP) -response element binding protein (CREB), as well as synapsin1 (Syn1) and synaptophysin (Syp) in the striatum of neonatal rats with hypoxic-ischemic brain damage (HIBD), so as to explore its mechanisms underlying improvement of motor control.

Seven-day-old neonatal SD rats were randomly and equally assigned to 4 groups: blank control, sham-operation, model, and acupuncture groups (n=12 per group) according to the randomized numerical table method. The HIBD model was established by using modified Rice’s method. For rats in the acupuncture group, manual acupuncture stimulation of“ Dazhui” (GV14),“ Baihui” (GV20), “Shuigou” (GV26) and “Mingmen” (GV4) was given 24 h after modeling. In the sham operation group, only the left common carotid artery was isolated without clamping, and no intervention was given. The neonatal rats in each group were subjected to the balance beam test 28 d after modeling. After the acupuncture intervention, the striatum tissue of neonatal rats in each group was taken for observing histopathological and morphological changes after H. E. staining. The ultrastructural changes of the neurons of striatum were observed by transmission electron microscopy, and the immunoactivity of Syp was detected by immunohistochemistry, and the expression levels of BDNF, TrkB, p-ERK, p-CREB, Syn1, and Syp proteins were detected by using Western blot.

There were no significant differences between the blank control and sham operation groups in the Longa score, balance beam test score, Syp immunoactivity, and expression levels of BDNF, TrkB, p-ERK, p-CREB, Syn1 and Syp proteins. Compared with the sham operation group, the balance beam test score at 28^th day after modeling was significantly increased (P＜0.01), and the Syp immunoactivity and the expression levels of BDNF, TrkB, p-ERK, p-CREB, Syn1 and Syp proteins were considerably down-regulated (P＜0.01, P＜0.05, P＜0.001) in the model group. In contrast to the model group, the balance beam test score at 28 d after modeling was obviously decreased (P＜0.05), the immunoactivity of Syp, and the expression levels of BDNF, TrkB, p-ERK, p-CREB, Syn1 and Syp proteins were strikingly up-regulated (P＜0.05, P＜0.01) in the acupuncture group. H.E. staining showed disordered arrangement of the striatal neurons, unclear layers, reduced cell density, with vacuolization and nuclear pyknosis in some cells in the model group, which was milder in the injury severity of the striatal neurons in the acupuncture group. Ultrastructure results displayed that in the model group, the distribution density of striatum synaptosome was lower, the thickness of postsynaptic dense area and the length of active area were reduced, and the boundary became blurred. Whereas in the acupuncture group, the synaptic structure of the striatum was more regular, the distribution density of synaptosomes, the thickness of the postsynaptic dense area and the length of the active area were increased.

Manual acupuncture stimulation can improve the motor control ability in neonatal rats with HIBD, which may be achieved by up-regulating the endogenous BDNF and its receptor TrkB, activating the MAPK/ERK signaling pathway, promoting the phosphorylation of CREB, and up-regulating the expression of Syn1 and Syp proteins, thereby promoting synaptic regeneration and remodeling.