Development of Autonomic Dysreflexia after Spinal Cord Injury Is Associated with a Lack of Serotonergic Axons in the Intermediolateral Cell Column
Development of Autonomic Dysreflexia after Spinal Cord Injury Is Associated with a Lack of Serotonergic Axons in the Intermediolateral Cell Column
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DOI：
10.1089/neu.2010.1441
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发表时间：
2010-10-01
影响因子：
4.2
通讯作者：
Marsh, Daniel R.
中科院分区：
文献类型：
--
作者：
Cormier, Christen M.;Mukhida, Karim;Marsh, Daniel R.
由于过度的脊髓交感神经兴奋，严重的上胸脊髓损伤(SCI)后，患者和大鼠的自主神经反射障碍持续发展。在本研究中，我们建立了不同程度脊髓损伤后的大鼠发作性高血压模型，以探讨5-羟色胺能球脊髓轴突在脊髓损伤后自主神经反射障碍发生中的作用。雌性Wistar大鼠(250-300g)用于以下所有实验：(1)未损伤组，(2)20、35、50g的T4夹压，(3)T4脊髓横断，(4)鞘内注射5，7-二羟色胺肌酸肌酸(5，7-DHT)。对T8~T12脊髓节段进行胆碱乙酰转移酶和5-羟色胺(5-HT)免疫组织化学染色，以确定交感节前神经元和中间外侧细胞柱(IMLC)内含5-羟色胺(5-HT)的轴突。通过测量安静时和结肠扩张引起的高血压后的平均动脉压(MAP)来测试自主神经反射障碍。我们观察到，结肠扩张后升压反应的大小与脊髓损伤的严重程度和IMLC中5-羟色胺免疫反应轴突的密度有关。鞘内注射5-羟色胺(2A)激动剂二甲氧基-4-碘苯丙胺可升高静息MAP并阻断结肠扩张诱导的高血压，而5-羟色胺(2A)拮抗剂酮色林降低静息MAP，并可抑制结肠扩张诱导的升压反应。这些结果表明，脊髓损伤后5-羟色胺能传入脊髓IMLC的丢失与脊髓损伤后自主神经反射障碍和低血压的发病机制成正比。因此，我们得出结论，保留超过临界阈值的5-羟色胺能轴突可以保护心血管调节，防止自主神经反射障碍的发展。
Autonomic dysreflexia consistently develops in patients and in rats after severe upper thoracic spinal cord injury (SCI) as a result of exaggerated spinal sympathetic excitation. In this study we induced episodic hypertension in rats after varying degrees of SCI severity to investigate the contribution of serotonergic bulbospinal axons to the development of autonomic dysreflexia after SCI. Female Wistar rats (250-300 g) were used in all experiments in the following groups: (1) uninjured, (2) clip compression at T4 of 20, 35, or 50 g, (3) spinal cord transection at T4, and (4) intrathecal 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT). Immunohistochemistry for choline acetyl transferase and serotonin (5-HT) was performed on T8-T12 spinal segments to identify sympathetic preganglionic neurons, and to assess 5-HT-containing axons in the intermediolateral cell column (IMLC), respectively. Testing for autonomic dysreflexia was conducted by measuring mean arterial pressure (MAP) at rest and after colon distension-induced hypertension. We observed that the magnitude of the pressor response seen after colon distension correlated with SCI severity and density of 5-HT-immunoreactive axons in the IMLC. Intrathecal administration of the 5-HT(2A) agonist dimethoxy-4-iodamphetamine increased resting MAP and blocked colon distension-induced hypertension, whereas the 5-HT(2A) antagonist ketanserin decreased resting MAP and was permissive to the colon distension-induced pressor response in SCI rats. These results suggest that the SCI-induced loss of serotonergic inputs into the spinal cord IMLC is proportional to the pathogenesis of autonomic dysreflexia and hypotension seen after SCI. We thus conclude that sparing of serotonergic axons beyond a critical threshold preserves cardiovascular regulation and prevents the development of autonomic dysreflexia.