Effects of rehabilitative training and anti-inflammatory treatment on functional recovery and cellular reorganization following stroke
Effects of rehabilitative training and anti-inflammatory treatment on functional recovery and cellular reorganization following stroke
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DOI：
10.1016/j.expneurol.2011.11.037
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发表时间：
2012-02-01
影响因子：
5.3
通讯作者：
Keiner, Silke
中科院分区：
文献类型：
--
作者：
Liebigt, Susan;Schlegel, Nadja;Keiner, Silke
缺血后炎症在卒中后细胞重组和功能恢复中起关键作用。因此，我们解决的假设，无论是消炎痛或米诺环素结合康复训练，改善功能恢复和影响病灶周围的细胞反应局灶性皮质梗死。使用成年大鼠的光血栓形成模型，在前肢和后肢感觉运动皮质中诱导局灶性皮质梗死。在实验的前2周，通过每天两次腹腔内应用吲哚美辛或米诺环素来阻断炎症过程。梗塞后，动物立即接受每日一次受损前肢的熟练伸展训练。另外，在梗塞后连续5天给予溴脱氧尿苷（BrdU）。在第14天和第42天，对病灶周围区的星形胶质细胞、小胶质细胞、未成熟和成熟神经元的增殖和分化进行免疫细胞化学定量。在术前和术后4、14和28天的感觉运动行走任务中评估功能恢复。联合康复训练和吲哚美辛或米诺环素强烈改善感觉运动性能，并显着减少增殖的小胶质细胞的数量相比，达到单独的训练。此外，该组合增加了增殖的星形胶质细胞的存活，此外，米诺环素增加了病灶周围区的双皮质素阳性细胞。与单独训练相比，抗炎药物应用与康复训练相结合可改善功能恢复，并显着改变皮质梗死附近不同胶质细胞和神经元亚群的增殖和存活。(C)2011 Elsevier Inc. All rights reserved.
Post-ischemic inflammation plays a critical role in cellular reorganization and functional recovery after stroke. We therefore address the hypothesis whether anti-inflammatory treatment with either indometacin or minocycline combined with rehabilitative training improve functional recovery and influence perilesional cellular response following focal cortical infarcts. Using the photothrombosis model in adult rats, focal cortical infarcts were induced in the fore- and hindlimb sensorimotor cortex. Inflammatory processes were blocked by intraperitoneal application of indometacin or minocycline twice daily during the first 2 weeks of the experiment. Immediately after the infarct, the animals received a daily session of skilled reaching training of the impaired forelimb. In addition, Bromodeoxyuridine (BrdU) was administrated for 5 sequential days post infarct. Proliferation and differentiation of astrocytes, microglia, immature and mature neurons in the perilesional zone were immunocytochemically quantified at days 14 and 42. Functional recovery was assessed in a sensorimotor walking task preoperatively and 4, 14 and 28 days post surgery. Combined rehabilitative training and indometacin or minocycline strongly improved sensorimotor performance and significantly reduced the number of proliferating microglia compared to reaching training alone. Furthermore, the combination increased the survival of proliferating astrocytes and, moreover, minocycline increased the doublecortin-positive cells in the perilesional zone. Anti-inflammatory drug application combined with rehabilitative training demonstrates improved functional recovery and significantly modifies proliferation and survival of distinct glial and neuronal subpopulations in the direct vicinity of cortical infarcts compared to reaching training alone. (C) 2011 Elsevier Inc. All rights reserved.