The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats.
The effects of cyclosporin-A on axonal conduction deficits following traumatic brain injury in adult rats.
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DOI：
10.1016/j.expneurol.2010.03.026
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发表时间：
2010-07
影响因子：
5.3
通讯作者：
Reeves, Thomas M.
中科院分区：
文献类型：
--
作者：
Colley, Beverly S.;Phillips, Linda L.;Reeves, Thomas M.
亲免素配体，包括环孢菌素-A（CsA），已被证明在创伤性脑损伤（TBI）的实验模型中具有神经保护作用，并减轻创伤性轴突损伤的严重程度。先前的研究已经记录了CsA治疗以减少创伤后轴突病理学的重要组成部分，包括受损的轴浆运输、血影蛋白水解和轴突肿胀。然而，CsA给药对轴突功能的影响，TBI后，尚未进行评估。本研究评估了CsA治疗对成年大鼠中线液压损伤后胼胝体诱发的复合动作电位（CAPs）的影响。大鼠在损伤后15 m或1 h接受20 mg/Kg CsA或Cremaphor载体的推注，并在损伤后24 h在冠状脑切片中进行CAP记录。为了阐明损伤和CsA治疗如何影响轴突的特定群体，将主要由有髓轴突（N1）产生的CAP波形与主要反映无髓轴突（N2）中的活性的CAP信号分开分析。CsA在伤后15 m给药导致CAP区的显著保护，并且这种作用在N1中比在N2，CAP组分中更明显。这种处理也显著地防止了TBI诱导的N1 CAP信号的高频响应的降低。相比之下，1小时的CsA治疗并未显着保护CAP，但与N1 CAP的非典型波形相关，包括CAP持续时间缩短和不应期降低。目前的研究结果也支持越来越多的证据表明，有髓和无髓轴突对损伤和神经保护化合物的反应不同。
Immunophilin ligands, including cyclosporin-A (CsA), have been shown to be neuroprotective in experimental models of traumatic brain injury (TBI), and to attenuate the severity of traumatic axonal injury. Prior studies have documented CsA treatment to reduce essential components of posttraumatic axonal pathology, including impaired axoplasmic transport, spectrin proteolysis, and axonal swelling. However, the effects of CsA administration on axonal function, following TBI, have not been evaluated. The present study assessed the effects of CsA treatment on compound action potentials (CAPs) evoked in corpus callosum of adult rats following midline fluid percussion injury. Rats received a 20 mg/Kg bolus of CsA, or cremaphor vehicle, at either 15 m or 1 h postinjury, and at 24 h postinjury CAP recording was conducted in coronal brain slices. To elucidate how injury and CsA treatments affect specific populations of axons, CAP waveforms generated largely by myelinated axons (N1) were analyzed separately from the CAP signal which predominantly reflects activity in unmyelinated axons (N2). CsA administration at 15 m postinjury resulted in significant protection of CAP area, and this effect was more pronounced in N1, than in the N2, CAP component. This treatment also significantly protected against TBI-induced reductions in high frequency responding of the N1 CAP signal. In contrast, CsA treatment at 1 h did not significantly protect CAPs, but was associated with atypical waveforms in N1 CAPs, including decreased CAP duration and reduced refractoriness. The present findings also support growing evidence that myelinated and unmyelinated axons respond differentially to injury and neuroprotective compounds.
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