Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
Biochem Biophys Res Commun. 2022 Aug 20;617(Pt 1):1-7. doi: 10.1016/j.bbrc.2022.05.002. Epub 2022 May 2.
Traumatic brain injury (TBI) is a closed or open head injury caused by external mechanical forces that induce brain damage, resulting in a wide range of postinjury dysfunctions of emotions, learning and memory, adversely affecting the quality of life of patients. In this study, we aimed to explore the possible mechanisms of NOX2 on cognitive deficits in a TBI mouse model. Behavioral tests were applied to evaluate learning and memory ability, and electrophysiological experiments were performed to measure synaptic transmission and intrinsic excitability of the CA1 pyramidal cells (PCs) and long-term potentiation (LTP) in the TBI hippocampus. We found that inhibitors of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) (GSK2795039 and apocynin) attenuate neurological deficits, facilitate long-term potentiation (LTP) and decrease spontaneous synaptic transmission and intrinsic excitability of CA1 pyramidal cells (PCs) in traumatic brain injury (TBI) mice. NOX2 mice display reduced learning and memory impairment, enhanced LTP and reduced spontaneous synaptic transmission and intrinsic excitability of PCs after TBI. Our study demonstrates that NOX2 is a potential target for learning and memory by modulating excitability and excitatory transmission in the hippocampus after TBI.
创伤性脑损伤（TBI）是由外部机械力引起的闭合性或开放性头部损伤，导致脑损伤，从而导致情绪、学习和记忆的广泛的损伤后功能障碍，对患者的生活质量产生不利影响。在本研究中，我们旨在探讨 NOX2 在 TBI 小鼠模型中认知缺陷的可能机制。应用行为测试评估学习和记忆能力，进行电生理实验测量 TBI 海马 CA1 锥体神经元（PCs）的突触传递和内在兴奋性以及长时程增强（LTP）。我们发现烟酰胺腺嘌呤二核苷酸磷酸氧化酶 2（NOX2）抑制剂（GSK2795039 和 apocynin）可减轻神经功能缺损，促进长时程增强（LTP），并降低创伤性脑损伤（TBI）小鼠 CA1 锥体神经元（PCs）的自发性突触传递和内在兴奋性。NOX2 小鼠在 TBI 后显示出学习和记忆损伤减轻、LTP 增强以及 PCs 的自发性突触传递和内在兴奋性降低。我们的研究表明，NOX2 是通过调节 TBI 后海马兴奋性和兴奋性传递来治疗学习和记忆的潜在靶点。
