The neural function repair and mechanism of (-)-epicatechin on murine traumatic brain injury

Objective To investigate whether (-)-epicatechin plays a role in neurological repair on traumatic brain injury in mice. Methods The mice model of traumatic brain injury was established by modified weight drop method. Experimental mice were randomly (random number) divided into the injury+ (Veh) group and the injury + (-)-epicatechin (EC) group. At 3 days after operation, the expression of IL-1β and TNF-α were detected. The number of necrotic cells of the lesion area was detected by PI staining. At 28 days after SCI, Morris Water Maze test was performed to observe the ability of spatial learning and memory in mice. The expression of neurotrophic factors BDNF and NGF were examined by qRT-PCR. The expression of NeuN was detected by immunofluorescence staining. EdU staining was used to observe the neurogenesis in the SGZ region. Results Compared with the Veh group, EC treated group showed better spatial learning and memory ability in time spent in correct quadrant at day 27 and 28 [24 d: (26.333±5.037)% vs (26.583±5.802)%, P=0.938; 25 d (33.300±4.724)% vs (29.767±3.347)%. P=0.166; 26 d: (41.017±7.246)% vs (32.800±8.145)%, P=0.095; 27 d: (48.017±7.424)% vs (35.267±6.748)%, P=0.011; 28 d: (51.617±9.017)% vs (41.116±6.467)%, P=0.043] and in latency to platform at day 27 and 28 [24 d: (62.967±5.494) s vs (63.917±7.027) s, P=0.800; 25 d: (50.533±10.305) s vs (57.217±13.085) s, P=0.349; 26 d: (40.333±10.526) s vs (50.133±11.039) s, P=0.147; 27 d: (28.717±4.137) s vs (44.533±7.181) s, P=0.001; 28 d: (21.950±6.889) s vs (37.567±5.974) s, P=0.002]. There was a decreased expression of IL-1β and TNF-α and increased level of neurotrophic factor BDNF and NGF after EC treatment in EC treatment group, compared to the veh treatment group [IL-1β and TNF-α: (42.690±3.057) ng/mL and (750.167±51.941) ng/mL vs (71.670±4.996) ng/mL and (1 085.167±68.535) ng/mL, P=0.000 6 and 0.003; BDNF and NGF: 0.543±0.033 and 0.334±0.041 vs 0.756±0.088 and 0.514±0.047, P=0.048 and 0.017)]. EC decreased the cell death near injury area (54.833±5.486 vs 74.000±5.323, P=0.031), increased NeuN positive cells (76.667±6.386 vs 42.167±5.237, P=0.002), and increased neurogenesis in SGZ area (12.667±0.760 vs 7.500±1.258, P=0.031). Conclusions (-)-Epicatechin plays an important role in functional recovery after traumatic brain injury in mice. The underlying mechanisms are closely related to inhibited inflammation, enhanced neurotrophic factors and improved neurogenesis. Key words: Traumatic brain injury; (-)-epicatechin; Nerve repair; Brain derived neurotrophic factor; Inflammation factors