Effects of Acute Intrathecal Baclofen in an Animal Model of TBI-Induced Spasticity, Cognitive, and Balance Disabilities
Effects of Acute Intrathecal Baclofen in an Animal Model of TBI-Induced Spasticity, Cognitive, and Balance Disabilities
复制标题
DOI：
10.1089/neu.2012.2740
复制
发表时间：
2013-07-01
影响因子：
4.2
通讯作者：
Thompson, Floyd J.
中科院分区：
文献类型：
--
作者：
Bose, Prodip;Hou, Jiamei;Thompson, Floyd J.
痉挛是创伤性脑损伤 (TBI) 患者的一个主要健康问题。除了痉挛之外，TBI 患者还表现出持久的认知、平衡和其他运动障碍。尽管使用抗痉挛药物，特别是 ITB，可以减轻 TBI 引起的痉挛的严重程度，但目前的指南不允许在 TBI 后的第一年使用 ITB。因此，本研究旨在量化 ITB 治疗后闭头 TBI 动物模型（cTBI；Mararou 模型）的残疾情况。 cTBI 后，检测到痉挛和步态、认知、平衡和焦虑样行为的显着缺陷。使用Alzet泵施用ITB（Lioresal (R)）或盐水（0.8μg/小时，持续4周）。在多个治疗后和撤回 ITB 时间点进行痉挛测量，使用速度依赖性踝关节扭矩和踝伸肌肌电图记录、足迹（步态）、平衡性能测试、连续学习和焦虑样行为。我们的数据表明，TBI 后第 1 周开始的 1 个月 ITB 治疗可阻止早期发作的痉挛，并显着减轻迟发性痉挛和焦虑样行为，对认知和平衡表现没有显着不利影响。这种痉挛症状的改善伴随着脊髓组织中γ-氨基丁酸（GABA）/GABA（b）、去甲肾上腺素和脑源性神经营养因子表达的显着上调。在这种 cTBI 动物模型中，早期干预 ITB 治疗是安全、可行且有效的。总的来说，这些数据提供了通过突触前抑制增强反射调节表达的强大分子足迹。讨论了急性 ITB 治疗可能减少节段适应不良和下降可塑性的可能性。本动物模型提供的数据启动了一个临床前平台，用于 TBI 后早期 ITB 干预的安全性、可行性和有效性。
Spasticity is a major health problem for patients with traumatic brain injury (TBI). In addition to spasticity, TBI patients exhibit enduring cognitive, balance, and other motor impairments. Although the use of antispastic medications, particularly ITB, can decrease the severity of TBI-induced spasticity, current guidelines preclude the use of ITB during the first year after TBI. Therefore, the present study was performed to quantitate disability in an animal model of closed-head TBI (cTBI; Mararou's model) after ITB treatment. After cTBI, significant deficits in spasticity and gait, cognitive, balance, and anxiety-like behaviors were detected. ITB (Lioresal (R)) or saline was administered using Alzet pumps (0.8 mu g/hour for 4 weeks). Spasticity measures using velocity-dependent ankle torque and ankle extensor muscle electromyography recordings, footprints (gait), balance performance tests, serial learning, and anxiety-like behaviors were performed at multiple post-treatment and -withdrawal of ITB time points. Our data indicated that 1 month of ITB treatment initiated at post-TBI week 1 blocked the early onset of spasticity and significantly attenuated late-onset spasticity and anxiety-like behavior with no significant adverse effects on cognitive and balance performance. This improved spasticity outcome was accompanied by marked up-regulation of gamma-aminobutyric acid (GABA)/GABA(b), norepinephrine, and brain-derived neurotrophic factor expression in spinal cord tissue. Early intervention with ITB treatment was safe, feasible, and effective in this cTBI animal model. Collectively, these data provide a strong molecular footprint of enhanced expression of reflex regulation by presynaptic inhibition. The possibility that acute ITB treatment may decrease maladaptive segmental and descending plasticity is discussed. The data provided by the present animal model initiates a pre-clinical platform for safety, feasibility, and efficacy of early ITB intervention after TBI.