COA-Cl 在脊髓损伤急性后期的保护作用及机制。

The protective effect and mechanism of COA-Cl in acute phase after spinal cord injury.

机构信息

Department of Physiology 2, Kawasaki Medical School, Matsushima, Kurashiki, Okayama, Japan; Department of Orthopedic Surgery, Kawasaki Medical School, Matsushima, Kurashiki, Okayama, Japan.

Department of Physiology 2, Kawasaki Medical School, Matsushima, Kurashiki, Okayama, Japan.

出版信息

Neurosci Res. 2021 Sep;170:114-121. doi: 10.1016/j.neures.2020.10.003. Epub 2020 Dec 11.

DOI:10.1016/j.neures.2020.10.003

PMID:33316301

Abstract

Spinal cord injury (SCI) induces severe motor and sensory dysfunction. We previously showed the neuroprotective effects of COA-Cl, a novel synthesized adenosine analog, in a rat stroke model. In this study, we evaluated the neuroprotective effects of COA-Cl in acute phase of SCI. SCI was induced in rats at the T9 vertebra by using a drop device. Rats were divided into acute and subacute groups. A 5-day dose of 6 mg/kg COA-Cl in saline was given to the acute group immediately after SCI and the subacute group 4 days after SCI. Motor function assessed by Basso-Beattie-Bresnahan scoring and inclined plane test improved significantly in the acute group while the subacute group did not. Histological evaluation and TUNEL staining revealed that both the cavity volume and apoptosis were significantly decreased in the acute group compared with the subacute group. In addition, pERK/ERK was increased in the acute group 7 days after SCI. These results suggest that COA-Cl exerts neuroprotective effects via the ERK pathway when administered in the acute phase after SCI, resulting in the recovery of motor function. COA-Cl could be a novel therapeutic agent for the acute phase of SCI.

摘要

脊髓损伤（SCI）会导致严重的运动和感觉功能障碍。我们之前在大鼠中风模型中显示了新型合成腺苷类似物 COA-Cl 的神经保护作用。在本研究中，我们评估了 COA-Cl 在急性 SCI 中的神经保护作用。通过落体装置在大鼠 T9 椎骨处诱导 SCI。大鼠分为急性组和亚急性组。急性组在 SCI 后立即给予 5 天剂量为 6mg/kg 的 COA-Cl 生理盐水，亚急性组在 SCI 后 4 天给予。Basso-Beattie-Bresnahan 评分和斜面试验评估的运动功能在急性组中明显改善，而亚急性组则没有。组织学评估和 TUNEL 染色显示，与亚急性组相比，急性组的腔体积和细胞凋亡明显减少。此外，pERK/ERK 在 SCI 后 7 天增加。这些结果表明，COA-Cl 在 SCI 后急性阶段通过 ERK 通路发挥神经保护作用，从而恢复运动功能。COA-Cl 可能是 SCI 急性阶段的一种新型治疗药物。