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联合 SCI 和 TBI:单侧颈脊髓损伤 (SCI) 后的前肢功能恢复会因对侧创伤性脑损伤 (TBI) 而延迟,同侧 TBI 则平衡了 SCI 对爪子放置的影响。

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

机构信息

Department of Neurological Surgery, University of California San Francisco, and San Francisco General Hospital, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, CA, USA.

出版信息

Exp Neurol. 2013 Oct;248:136-47. doi: 10.1016/j.expneurol.2013.06.006. Epub 2013 Jun 13.

Abstract

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI.

摘要

相当一部分(估计范围从 16%到 74%)脊髓损伤(SCI)患者伴有创伤性脑损伤(TBI),这种组合常常给康复策略和药物治疗的规划和实施带来困难。例如,许多用于治疗 SCI 的药物可能会干扰认知康复,而用于控制 TBI 患者癫痫发作的药物可能会破坏 SCI 后的运动恢复。本文提出了一种用于 SCI 和 TBI 联合损伤的实验动物模型,以帮助推动双重诊断的机制研究。大鼠在 C5 椎体水平接受单侧 SCI(75 kdyn)、单侧 TBI(2.0 毫米深度,4.0 米/秒速度撞击前肢感觉运动皮层)或 SCI+TBI 联合损伤。TBI 放置在 SCI 的对侧或同侧。使用圆筒中爪放置、梳理、开阔场运动和 IBB 麦片进食测试来检查行为恢复情况。在 6 周的时间里,在爪放置测试中,SCI+对侧 TBI 产生了严重的缺陷,无法恢复,但 SCI+同侧 TBI 增加了 SCI 侧爪的相对使用。在梳理测试中,SCI+对侧 TBI 产生的恢复比单独损伤更差,尽管单独对侧 TBI 没有观察到明显的缺陷。在 IBB 前肢测试中,SCI+对侧 TBI 显示出严重的缺陷,3 周后恢复。对于开阔场运动,SCI 单独或与 TBI 联合作用导致最初的缺陷,2 周后恢复。因此,TBI 和 SCI 对前肢功能的影响因测试而异,反映了例如探索性爪放置和刻板梳理的不同神经基础。根据两个损伤的侧位,并发 SCI 和 TBI 对结果和恢复有显著不同的影响。在所有测试中,在对侧半球添加中等 TBI 都会延迟颈 SCI 后的功能恢复,但同侧 TBI 会使前爪的放置相对于 SCI 单独增加,这可能是由于双重竞争损伤影响了两只前肢的使用。这些发现强调了联合中枢神经系统损伤恢复的复杂性,以及可塑性和侧位在康复中的可能作用,并为评估 SCI 和 TBI 联合治疗的有效疗法提供了一个有用的临床前模型的开端。

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