Poststroke delivery of MANF promotes functional recovery in rats.
Poststroke delivery of MANF promotes functional recovery in rats.
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DOI：
10.1126/sciadv.aap8957
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发表时间：
2018-05
期刊：
影响因子：
13.6
通讯作者：
Airavaara M
中科院分区：
文献类型：
--
作者：
Mätlik K;Anttila JE;Kuan-Yin T;Smolander OP;Pakarinen E;Lehtonen L;Abo-Ramadan U;Lindholm P;Zheng C;Harvey B;Arumäe U;Lindahl M;Airavaara M
缺血性脑卒中后延迟向大鼠脑输送MANF可促进功能恢复并招募吞噬免疫细胞。中风是发达国家成人致残最常见的原因，很大程度上是因为自发恢复往往是不完全的，并且没有药物手段来加速恢复。最近的研究表明，中脑星形细胞衍生神经营养因子（MANF）可诱导果蝇和小鼠视网膜损伤后免疫细胞的选择性或M2激活，并介导视网膜修复。因此，我们开始研究脑卒中后MANF b政府将是否能促进脑组织修复并影响脑缺血损伤大鼠的行为恢复。我们使用脑缺血再灌注损伤的大脑中动脉远端闭塞（dMCAo）模型，并将MANF作为重组蛋白或通过腺相关病毒（AAV）载体给予。我们发现，在中风后2 - 3天给药于梗死周围区域时，它促进了动物的功能恢复，而不影响病变体积。此外，AAV7-MANF治疗瞬时增加皮层下梗死周围区域吞噬巨噬细胞的数量。此外，对敲除小鼠的分析揭示了内源性MANF对缺血性损伤的神经保护作用，尽管内源性MANF对免疫细胞相关基因表达没有影响。MANF治疗对逆转中风引起的行为缺陷的有益作用表明，基于MANF的疗法可用于中风后脑组织的修复。
Delayed delivery of MANF to rat brain after ischemic stroke promotes functional recovery and recruits phagocytic immune cells. Stroke is the most common cause of adult disability in developed countries, largely because spontaneous recovery is often incomplete, and no pharmacological means to hasten the recovery exist. It was recently shown that mesencephalic astrocyte–derived neurotrophic factor (MANF) induces alternative or M2 activation of immune cells after retinal damage in both fruit fly and mouse and mediates retinal repair. Therefore, we set out to study whether poststroke MANF administration would enhance brain tissue repair and affect behavioral recovery of rats after cerebral ischemic injury. We used the distal middle cerebral artery occlusion (dMCAo) model of ischemia-reperfusion injury and administered MANF either as a recombinant protein or via adeno-associated viral (AAV) vector. We discovered that, when MANF was administered to the peri-infarct region 2 or 3 days after stroke, it promoted functional recovery of the animals without affecting the lesion volume. Further, AAV7-MANF treatment transiently increased the number of phagocytic macrophages in the subcortical peri-infarct regions. In addition, the analysis of knockout mice revealed the neuroprotective effects of endogenous MANF against ischemic injury, although endogenous MANF had no effect on immune cell–related gene expression. The beneficial effect of MANF treatment on the reversal of stroke-induced behavioral deficits implies that MANF-based therapies could be used for the repair of brain tissue after stroke.
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MANF免疫调节可促进视网膜的组织修复和再生成功。
DOI：
10.1126/science.aaf3646
发表时间：
2016-07-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Neves J;Zhu J;Sousa-Victor P;Konjikusic M;Riley R;Chew S;Qi Y;Jasper H;Lamba DA
通讯作者：
Lamba DA
影响因子：
158.5
作者：
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通讯作者：
Dobkin, BH
影响因子：
3.5
作者：
Lindholm, Paivi;Peranen, Johan;Saarma, Mart
通讯作者：
Saarma, Mart
影响因子：
11.2
作者：
Lindsberg, PJ;Ohman, J;Meri, S
通讯作者：
Meri, S
影响因子：
6.1
作者：
Runeberg-Roos, Pia;Piccinini, Elisa;Saarma, Mart
通讯作者：
Saarma, Mart