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干细胞治疗改善中风后神经功能预后:雄性和雌性大鼠的对比研究。

Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats.

机构信息

Cancer Biology and Pharmacology, College of Medicine, University of Illinois, Peoria, Illinois, USA.

Pharmaceutical and Biomedical Sciences, California Health Sciences University, Clovis, California, USA.

出版信息

Stroke Vasc Neurol. 2021 Dec;6(4):519-527. doi: 10.1136/svn-2020-000834. Epub 2021 Mar 19.

Abstract

BACKGROUND AND PURPOSE

The therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.

METHODS

Transient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.

RESULTS

The infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).

CONCLUSIONS

Despite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

摘要

背景与目的

不同干细胞治疗缺血性中风的治疗潜力令人着迷,也存在一些争议。我们实验室最近的研究结果表明,人脐带血来源的间充质干细胞(MSC)在啮齿动物中风模型中具有潜在的益处。我们假设 MSC 治疗将有效地促进雄性和雌性动物的感觉和运动功能恢复,尽管中风后大脑损伤在雄性和雌性中存在明显的性别差异。

方法

通过阻断大脑中动脉,在成年 Sprague-Dawley 大鼠中诱导短暂性局灶性脑缺血。在手术后,未经处理的雄性和雌性大鼠在再灌注后 1 天被安乐死,其大脑用于估计梗死体积和组织肿胀。另外,一些诱导中风的雄性和雌性大鼠被 MSC 或载体处理,随后接受一系列标准的神经/神经行为学测试(改良神经严重程度评分评估、胶带去除、横梁行走和转棒)。这些测试在再灌注后定期进行(第 1、3、5、7 和 14 天),以确定中风后神经和功能恢复的时间过程。

结果

雄性和雌性大鼠的梗死体积和缺血性大脑肿胀程度相似。尽管病理中风损伤相似,但中风的临床表现在雄性中比在雌性中更为明显,这表明神经评分和其他测试表明。MSC 治疗显著改善了雄性和雌性的感觉和运动功能恢复,并且在中度中风(雌性)和重度中风(雄性)中都表现出疗效。

结论

尽管中风后结局的严重程度存在性别差异,但 MSC 治疗促进了雄性和雌性大鼠的感觉和运动功能恢复,这表明它可能是一种有前途的中风治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a58b/8717804/4c742739e850/svn-2020-000834f01.jpg

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