Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury
Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury
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DOI：
10.1016/j.expneurol.2005.10.003
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发表时间：
2006-02-01
影响因子：
5.3
通讯作者：
Povlishock, JT
中科院分区：
文献类型：
--
作者：
Marmarou, CR;Povlishock, JT
创伤性脑损伤（TBI）后的创伤性轴索损伤（TAI）仍然是一个临床问题，目前尚无有效的治疗方法。TAI被认为涉及轴突内的变化，普遍导致受损的轴突运输（IAT），断开和轴突球的形成。然而，最近的免疫细胞化学研究采用淀粉样前体蛋白（APP）抗体，IAT的标记物和神经丝致密化（NFC）抗体，RM 014，证明NFC通常发生独立于IAT，表明存在不同的受损轴突群体。已证明FK 506给药可减弱IAT。然而，鉴于上述情况，需要对FK 506减弱表现NFC的轴突损伤的能力进行评价。目前的研究探索了FK 506减弱两种受损轴突群体的潜力。大鼠在损伤前30 min给予FK 506（3 mg/kg）或溶剂。TBI后3小时，制备组织以使用靶向IAT（APP）或NFC（RM 014）的抗体或组合标记策略使TAI可视化。与以前的报道一致，FK 506治疗减少了CSpT中IAT的轴突数量，从411 +/- 54.70减少到91.00 +/- 33.87（P
Traumatic axonal injury (TAI) following traumatic brain injury (TBI) remains a clinical problem for which no effective treatment exists. TAI was thought to involve intraaxonal changes that universally led to impaired axonal transport (IAT), disconnection and axonal bulb formation. However, recent, immunocytochemical studies employing antibodies to amyloid precursor protein (APP), a marker of IAT and antibodies to neurofilament compaction (NFC), RM014, demonstrated that NFC typically occurs independent of IAT, indicating the existence of different populations of damaged axons. FK506 administration has been shown to attenuate IAT. However, in light of the above, the ability of FK506 to attenuate axonal damage demonstrating NFC requires evaluation. The Current study explored the potential of FK506 to attenuate both populations of damaged axons. Rats were administered FK506 (3 mg/kg) or vehicle 30 min preinjury. Three hours post-TBI, tissue was prepared for the visualization of TAI using antibodies targeting IAT (APP) or NFC (RM014) or a combined labeling strategy. Confirming previous reports, FK506 treatment reduced the number of axons demonstrating IAT in the CSpT, from 411 +/- 54.70 to 91.00 +/- 33.87 (P