Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland; Department of Neurology, Kuopio University Hospital, PO Box 1777, FI-70211 Kuopio, Finland.
Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland.
Epilepsy Res. 2014 May;108(4):653-65. doi: 10.1016/j.eplepsyres.2014.02.001. Epub 2014 Feb 8.
In a subgroup of patients, traumatic brain injury (TBI) results in the occurrence of acute epileptic seizures or even status epilepticus, which are treated with antiepileptic drugs (AEDs). Recent experimental data, however, suggest that administration of AEDs at the early post-injury phase can compromise the recovery process. The present study was designed to assess the profile of a novel anticonvulsant, lacosamide (Vimpat) on post-TBI structural, motor and cognitive outcomes. Moderate TBI was induced by lateral fluid-percussion injury in adult rats. Treatment with 0.9% saline or lacosamide (30 mg/kg, i.p.) was started at 30 min post-injury and continued at 8h intervals for 3d (total daily dose 90 mg/kg/d). Rats were randomly assigned to 4 treatment groups: sham-operated controls treated with vehicle (Sham-Veh) or lacosamide (Sham-LCM) and injured animals treated with vehicle (TBI-Veh) or lacosamide (TBI-LCM). As functional outcomes we tested motor recovery with composite neuroscore and beam-walking at 2, 7, and 15 d post-injury. Cognitive recovery was tested with the Morris water-maze at 12-14 d post-TBI. To assess the structural outcome, animals underwent magnetic resonance imaging (MRI) at 2 d post-TBI. At 16d post-TBI, rats were perfused for histology to analyze cortical and hippocampal neurodegeneration and axonal damage. Our data show that at 2 d post-TBI, both the TBI-Veh and TBI-LCM groups were equally impaired in neuroscore. Thereafter, motor recovery occurred similarly during the first week. At 2 wk post-TBI, recovery of the TBI-LCM group lagged behind that in the TBI-VEH group (p<0.05). Performance in beam-walking did not differ between the TBI-Veh and TBI-LCM groups. Both TBI groups were similarly impaired in the Morris water-maze at 2 wk post-TBI. MRI and histology did not reveal any differences in the cortical or hippocampal damage between the TBI-Veh and TBI-LCM groups. Taken together, acute treatment with LCM had no protective effects on post-TBI structural or functional impairment. Composite neuroscore in the TBI-LCM group lagged behind that in the TBI-Veh group at 15 d post-injury, but no compromise was found in other indices of post-TBI recovery in the LCM treated animals.
在一部分患者中，创伤性脑损伤（TBI）会导致急性癫痫发作甚至癫痫持续状态，需要使用抗癫痫药物（AEDs）进行治疗。然而，最近的实验数据表明，在受伤后早期使用 AED 会损害恢复过程。本研究旨在评估新型抗惊厥药拉考沙胺（Vimpat）对 TBI 后结构、运动和认知结果的影响。通过侧方液压冲击伤诱导成年大鼠中度 TBI。在损伤后 30 分钟开始用 0.9%生理盐水或拉考沙胺（30mg/kg，腹腔注射）治疗，每 8 小时一次，持续 3 天（总日剂量 90mg/kg/d）。大鼠随机分为 4 个治疗组：假手术对照组用载体（假手术对照-Veh）或拉考沙胺（假手术对照-LCM）处理，损伤动物用载体（TBI-Veh）或拉考沙胺（TBI-LCM）处理。作为功能结果，我们在损伤后 2、7 和 15 天用复合神经评分和束棒行走测试运动恢复。在 TBI 后 12-14 天用 Morris 水迷宫测试认知恢复。为了评估结构结果，动物在 TBI 后 2 天进行磁共振成像（MRI）检查。在 TBI 后 16 天，大鼠灌注进行组织学分析，以分析皮质和海马神经退行性变和轴突损伤。我们的数据显示，在 TBI 后 2 天，TBI-Veh 和 TBI-LCM 组的神经评分均受损。此后，在第一周内，运动恢复情况相似。在 TBI 后 2 周，TBI-LCM 组的恢复落后于 TBI-VEH 组（p<0.05）。束棒行走测试中，TBI-Veh 和 TBI-LCM 组之间的表现没有差异。在 TBI 后 2 周，Morris 水迷宫测试中，两组均受损。MRI 和组织学检查未发现 TBI-Veh 和 TBI-LCM 组之间皮质或海马损伤有任何差异。总之，急性 LCM 治疗对 TBI 后结构或功能损伤没有保护作用。TBI-LCM 组的复合神经评分在损伤后 15 天落后于 TBI-Veh 组，但在 LCM 治疗动物的 TBI 后恢复的其他指标中没有发现任何缺陷。
