Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic acid: translational application for paralysis, spasticity and pain.
Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic acid: translational application for paralysis, spasticity and pain.
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DOI：
10.1371/journal.pone.0026107
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Taylor J
中科院分区：
文献类型：
--
作者：
Avila-Martin G;Galan-Arriero I;Gómez-Soriano J;Taylor J
不完全性脊髓损伤（iSCI）后的感觉运动功能障碍通常以瘫痪、痉挛和疼痛的衰弱症状为特征，这需要用新型多效性药物治疗。以往的体外研究表明，白蛋白（Alb）和油酸（OA）可能作为内源性神经营养因子共同发挥作用。虽然Alb可以促进iSCI后运动功能的基本恢复，但OA或Alb-OA对与痉挛症状和伤害感受变化相关的SCI已知平移测量的治疗效果尚未研究。在Wistar大鼠的T9脊髓挫伤后，鞘内治疗：i）生理盐水，ii）白蛋白（0.4纳摩尔），iii）OA（80纳摩尔），iv）Alb-弹性体酸（0.4/80纳摩尔），或（0.4/80纳摩尔）的基本运动功能，伤害性反射活动的时间总和，并在受伤后一个月内对SCI以下的脊髓活动进行了下行调节的新测试。白蛋白、OA和Alb-OA处理抑制伤害性胫骨前肌（TA）反射活动。此外，在iSCI上方施加非侵入性电条件刺激后，Alb-OA协同促进运动活动的早期恢复至对照的50±10%，并促进TA伤害性反射活动的从头阶段性下降抑制至47±5%。脊髓L4-L5免疫组织化学显示，与未损伤组织相比，Alb-OA处理后，背角和腹角内的5-羟色胺纤维神经支配独特增加，分别高达4.2±1.1和2.3±0.3倍，此外NR 1 NMDA受体磷酸化和小胶质细胞反应性降低。在Alb-OA治疗后，通过已知的内源性脊髓作用机制介导，自愿运动功能的早期恢复伴随着对伤害性TA屈肌反射活动的强直性和从头阶段性下降抑制，表明这种新型神经营养因子用于治疗麻痹、痉挛和疼痛的临床应用。
Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50±10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47±5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4–L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2±1.1 and 2.3±0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain.
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影响因子：
3.1
作者：
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通讯作者：
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