Development of AMPA receptor and GABA B receptor-sensitive spinal hyper-reflexia after spinal air embolism in rat: a systematic neurological, electrophysiological and qualitative histopathological study.
Development of AMPA receptor and GABA B receptor-sensitive spinal hyper-reflexia after spinal air embolism in rat: a systematic neurological, electrophysiological and qualitative histopathological study.
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DOI：
10.1016/j.expneurol.2012.06.004
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发表时间：
2012-09
影响因子：
5.3
通讯作者：
Marsala, Martin
中科院分区：
文献类型：
--
作者：
Kakinohana, Osamu;Scadeng, Miriam;Corleto, Jose A.;Sevc, Juraj;Lukacova, Nadezda;Marsala, Martin
关键词：
减压病是由动脉和静脉系统中的气泡形成，导致脊髓播散性神经退行性改变引起的，临床上可表现为运动功能障碍、脊柱节段性伸展反射亢进(即痉挛)和肌肉僵硬。在我们目前的研究中，我们描述了一种脊髓空气栓塞的大鼠模型，其特征是发展为类似的脊髓播散性神经退行性改变和功能缺陷。此外，对全身AMPA受体拮抗剂(NGX424)和GABA B受体激动剂(巴氯芬)的抗痉挛作用进行了研究。为建立脊髓空气栓塞症模型，动物经主动脉内注入空气(50~200μL/kg)。栓塞后，用计算机控制的踝关节旋转测量痉挛的发展情况。接受150或200μL主动脉内空气注射的动物在5~7天出现运动障碍，并出现痉挛(50%~60%)或松弛(25%~35%)截瘫。MRI和脊椎组织病理学分析显示下胸至骶椎节段弥漫性脊髓梗塞。NGX424或巴氯芬的治疗提供了有效的抗痉挛效果(即伸展反射抑制)。该模型为研究空气栓塞性脊髓损伤的病理生理学提供了一个有价值的实验工具，并允许评估针对调节脊髓空气栓塞性神经症状的新的治疗效果。
Decompression sickness results from formation of bubbles in the arterial and venous system, resulting in spinal disseminated neurodegenerative changes and may clinically be presented by motor dysfunction, spinal segmental stretch hyper-reflexia (i.e., spasticity) and muscle rigidity. In our current study, we describe a rat model of spinal air embolism characterized by the development of similar spinal disseminated neurodegenerative changes and functional deficit. In addition, the anti-spastic potency of systemic AMPA receptor antagonist (NGX424) or GABA B receptor agonist (baclofen) treatment was studied. To induce spinal air embolism, animals received an intra-aortic injection of air (50–200 μl/kg). After embolism, the development of spasticity was measured using computer-controlled ankle rotation. Animals receiving 150 or 200 μl of intra-aortic air injections displayed motor dysfunction with developed spastic (50–60% of animals) or flaccid (25–35% of animals) paraplegia at 5–7 days. MRI and spinal histopathological analysis showed disseminated spinal cord infarcts in the lower thoracic to sacral spinal segments. Treatment with NGX424 or baclofen provided a potent anti-spasticity effect (i.e., stretch hyper-reflexia inhibition). This model appears to provide a valuable experimental tool to study the pathophysiology of air embolism-induced spinal injury and permits the assessment of new treatment efficacy targeted to modulate neurological symptoms resulting from spinal air embolism.
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5.3
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通讯作者：
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