Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke.
Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke.
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DOI：
10.1002/glia.22723
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发表时间：
2014-12
期刊：
影响因子：
6.2
通讯作者：
Chopp, Michael
中科院分区：
文献类型：
--
作者：
Liu, Zhongwu;Li, Yi;Cui, Yisheng;Roberts, Cynthia;Lu, Mei;Wilhelmsson, Ulrika;Pekny, Milos;Chopp, Michael
脑卒中后反应性星形胶质细胞的功能作用是有争议的。为了阐明反应性星形胶质细胞是否有助于神经恢复，我们比较了野生型（WT）和胶质纤维酸性蛋白/波形蛋白双敲除（GFAP - / - Vim - / -）小鼠在右前肢运动区受到玫瑰红诱导的大脑皮质光血栓性中风后的行为结果、皮质脊髓束（CST）轴突重塑以及硫酸软骨素蛋白聚糖（CSPG）表达的时空变化。在中风前和中风后第3天分别进行足断层试验和单颗粒到达试验，此后每周进行一次，以监测功能缺陷和恢复情况。将生物素化右旋糖酐胺（BDA）注入左运动皮层，顺行标记CST轴突。与WT小鼠相比，GFAP - / - Vim - / -小鼠颈灰质失神经侧运动功能恢复和bda阳性CST轴突长度显著减少（n = 10/组，P <0.01）。免疫组织学数据显示，在星形细胞反应性减弱的GFAP - / - Vim - / -小鼠中，与WT小鼠相比，CSPG在两个半球病变远端区域的表达显著增加，但在缺血病变边界区表达明显减少（n = 12/组，P <0.001）。我们的数据表明，星形细胞反应性减弱通过减少去神经脊髓的CST轴突重塑而损害或延迟神经恢复。因此，脑卒中后星形细胞反应性的操纵可能代表神经恢复策略的治疗目标。
The functional role of reactive astrocytes after stroke is controversial. To elucidate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST), and the spatio-temporal change of chondroitin sulfate proteoglycan (CSPG) expression between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP−/−Vim−/−) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the CST axons. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP−/−Vim−/− mice (n = 10/group, P <0.01). Immunohistological data showed that in GFAP−/−Vim−/− mice, in which astrocytic reactivity is attenuated, CSPG expression was significantly increased in the lesion remote areas in both hemispheres, but decreased in the ischemic lesion boundary zone, compared with WT mice (n = 12/group, P <0.001). Our data suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord. Thus, manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies.
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影响因子：
3.7
作者：
Berg A;Zelano J;Pekna M;Wilhelmsson U;Pekny M;Cullheim S
通讯作者：
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影响因子：
25
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