Traumatic brain injury (TBI) can produce lasting cognitive, emotional, and somatic difficulties that can impact quality of life for patients living with an injury. Impaired hippocampal function and synaptic alterations have been implicated in contributing to cognitive difficulties in experimental TBI models. In the synapse, neuronal communication is facilitated by the regulated release of neurotransmitters from docking presynaptic vesicles. The synaptic vesicle glycoprotein 2 (SV2) isoforms SV2A and SV2B play central roles in the maintenance of the readily releasable pool of vesicles and the coupling of calcium to the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex responsible for vesicle docking. Recently, we reported the findings of TBI-induced reductions in presynaptic vesicle density and SNARE complex formation; however, the effect of TBI on SV2 is unknown. To investigate this, rats were subjected to controlled cortical impact (CCI) or sham control surgery. Abundance of SV2A and SV2B were assessed at 1, 3, 7, and 14 days post-injury by immunoblot. SV2A and SV2B were reduced in the cortex at several time points and in the hippocampus at every time point assessed. Immunohistochemical staining and quantitative intensity measurements completed at 14 days post-injury revealed reduced SV2A immunoreactivity in all hippocampal subregions and reduced SV2B immunoreactivity in the molecular layer after CCI. Reductions in SV2A abundance and immunoreactivity occurred concomitantly with motor dysfunction and spatial learning and memory impairments in the 2 weeks post-injury. These findings provide novel evidence for the effect of TBI on SV2 with implications for impaired neurotransmission neurobehavioral dysfunction after TBI.

创伤性脑损伤 (TBI) 会产生持久的认知、情感和躯体困难，从而影响受伤患者的生活质量。海马功能受损和突触改变与实验性 TBI 模型中的认知困难有关。在突触中，神经元通讯通过对接突触前小泡调节释放神经递质来促进。突触小泡糖蛋白 2 (SV2) 同种型 SV2A 和 SV2B 在维持易释放的小泡池和钙与N负责囊泡对接的-乙基马来酰亚胺敏感因子附着蛋白受体 (SNARE) 复合物。最近，我们报道了 TBI 诱导的突触前囊泡密度和 SNARE 复合物形成减少的结果。然而，TBI 对 SV2 的影响尚不清楚。为了研究这一点，大鼠接受了受控皮质冲击 (CCI) 或假控制手术。通过免疫印迹在损伤后 1、3、7 和 14 天评估 SV2A 和 SV2B 的丰度。SV2A 和 SV2B 在几个时间点在皮质中减少，在每个评估的时间点在海马中减少。损伤后 14 天完成的免疫组织化学染色和定量强度测量显示所有海马亚区的 SV2A 免疫反应性降低，CCI 后分子层的 SV2B 免疫反应性降低。SV2A 丰度和免疫反应性的降低伴随着受伤后 2 周内的运动功能障碍和空间学习和记忆障碍。这些发现为 TBI 对 SV2 的影响提供了新的证据，对 TBI 后受损的神经传递神经行为功能障碍有影响。