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创新性模拟人类脊髓损伤特征的小鼠模型:二十二碳六烯酸对急慢性期的疗效。

Innovative mouse model mimicking human-like features of spinal cord injury: efficacy of Docosahexaenoic acid on acute and chronic phases.

机构信息

CNR - National Research Council, Institute of Cell Biology and Neurobiology, 00015, Monterotondo Scalo, Italy.

IRCCS - Santa Lucia Foundation, 00143, Roma, Italy.

出版信息

Sci Rep. 2019 Jun 20;9(1):8883. doi: 10.1038/s41598-019-45037-x.

Abstract

Traumatic spinal cord injury has dramatic consequences and a huge social impact. We propose a new mouse model of spinal trauma that induces a complete paralysis of hindlimbs, still observable 30 days after injury. The contusion, performed without laminectomy and deriving from the pressure exerted directly on the bone, mimics more closely many features of spinal injury in humans. Spinal cord was injured at thoracic level 10 (T10) in adult anesthetized female CD1 mice, mounted on stereotaxic apparatus and connected to a precision impactor device. Following severe injury, we evaluated motor and sensory functions, and histological/morphological features of spinal tissue at different time points. Moreover, we studied the effects of early and subchronic administration of Docosahexaenoic acid, investigating functional responses, structural changes proximal and distal to the lesion in primary and secondary injury phases, proteome modulation in injured spinal cord. Docosahexaenoic acid was able i) to restore behavioural responses and ii) to induce pro-regenerative effects and neuroprotective action against demyelination, apoptosis and neuroinflammation. Considering the urgent health challenge represented by spinal injury, this new and reliable mouse model together with the positive effects of docosahexaenoic acid provide important translational implications for promising therapeutic approaches for spinal cord injuries.

摘要

外伤性脊髓损伤后果严重,对社会影响巨大。我们提出了一种新的小鼠脊髓创伤模型,可导致后肢完全瘫痪,损伤 30 天后仍可观察到。这种挫伤无需椎板切除术,直接作用于骨骼产生压力,更能模拟人类脊髓损伤的许多特征。在麻醉的雌性 CD1 小鼠胸 10 水平(T10)的脊髓上进行撞击,将其固定在立体定位仪上,连接到精密撞击装置。严重损伤后,我们在不同时间点评估运动和感觉功能以及脊髓组织的组织学/形态学特征。此外,我们研究了二十二碳六烯酸(Docosahexaenoic acid)的早期和亚慢性给药的效果,研究了在原发性和继发性损伤阶段,损伤脊髓中近端和远端的功能反应、结构变化以及蛋白质组的调节。二十二碳六烯酸能够:i)恢复行为反应,ii)诱导促再生作用和神经保护作用,对抗脱髓鞘、细胞凋亡和神经炎症。考虑到脊髓损伤带来的紧迫健康挑战,这种新型可靠的小鼠模型以及二十二碳六烯酸的积极作用,为脊髓损伤的有前景的治疗方法提供了重要的转化意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee39/6586623/c82cf27850bf/41598_2019_45037_Fig1_HTML.jpg

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