Celal Bayar University School of Medicine Neurosurgery Department/Turkey.
Manisa Celal Bayar University School of Medicine Physiology Department/Turkey.
Injury. 2021 Apr;52(4):713-723. doi: 10.1016/j.injury.2021.02.055. Epub 2021 Mar 3.
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI can be classified based on severity, mechanism or other features. Inflammation, apoptosis, oxidative stress, and ischemia are some of the important pathophys-iological mechanisms underlying neuronal loss after TBI. Lacosamide (LCM) is an anticonvulsant compound approved for the adjunctive treatment of partial-onset seizures and neuropathic pain. This study aimed to investigate possible neuroprotective effects of LCM in a rat model of TBI.
Twenty-eight adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the control group (n=7). Group 2 was the trauma group (n=7) where rats were treated with 100 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 6 (group 3, n=7) or 20 (group 4, n=7) mg/kg Lacosamide IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. In addition, electroencephalograpy monitoring results were compared.
The immunoreactivity of both iNOS and eNOS (oxidative stress markers) were decreased with LCM treatment compared to trauma group. The results were statistically significant (***P<0.001). The treatments of low (56,17±9,69) and high-dose LCM (43,91±9,09) were decreased the distribution of HIF-1α compared to trauma group (P<0.01). The number of apoptotic cells were decreased with LCM treatment the difference between the trauma group and 20mg/kg LCM treated group (9,55±1,02) was statistically significant (***P<0.001). Malondialdehyde level was reduced with LCM treatment. MDA level was significantly higher in trauma group compared to LCM treated groups (***P<0.001). The level of Superoxide dismutase in the trauma group was 1,86 U/ml, whereas it was 36,85 U/ml in 20mg/kg LCM treated group (***P<0.001). Delta strength of EEG in 20mg/kg LCM treated group were similar to control group values after LCM treatment.
No existing study has produced results suggesting that different doses of LCM has therapeutic effect against TBI, using EEG recording in addition to histological and biochemical evaluations in rats.
创伤性脑损伤（TBI）是全球范围内导致死亡和残疾的主要原因，尤其是在儿童和青少年中。TBI 可以根据严重程度、机制或其他特征进行分类。炎症、细胞凋亡、氧化应激和缺血是 TBI 后神经元丢失的一些重要病理生理机制。拉科酰胺（LCM）是一种批准用于辅助治疗部分发作性癫痫和神经性疼痛的抗惊厥化合物。本研究旨在探讨 LCM 在 TBI 大鼠模型中的可能神经保护作用。
使用 28 只成年雄性 Wistar 白化大鼠。将大鼠分为 4 组。第 1 组为对照组（n=7）。第 2 组为创伤组（n=7），大鼠每天腹腔注射 100mg/kg 生理盐水两次。第 3 组（n=7）和第 4 组（n=7）大鼠每天腹腔注射 6 或 20mg/kg 拉科酰胺两次。对于每组，在损伤后 72 小时收集脑样本。通过组织病理学和生化方法评估脑样本和血液。此外，还比较了脑电图监测结果。
与创伤组相比，LCM 治疗降低了 iNOS 和 eNOS 的免疫反应性（氧化应激标志物）。结果具有统计学意义（***P<0.001）。与创伤组相比，低剂量（56.17±9.69）和高剂量 LCM（43.91±9.09）治疗降低了 HIF-1α 的分布（P<0.01）。LCM 治疗减少了凋亡细胞的数量，创伤组与 20mg/kg LCM 治疗组之间的差异具有统计学意义（***P<0.001）。LCM 治疗降低了丙二醛水平。与 LCM 治疗组相比，创伤组的 MDA 水平显著升高（***P<0.001）。创伤组超氧化物歧化酶水平为 1.86U/ml，而 20mg/kg LCM 治疗组为 36.85U/ml（***P<0.001）。LCM 治疗后，20mg/kg LCM 治疗组的 EEG 强度差值与对照组相似。
没有现有研究表明，使用脑电图记录除组织学和生化评估外，不同剂量的 LCM 对 TBI 具有治疗作用。
