Müller Harald D, Hanumanthiah Kiran M, Diederich Kai, Schwab Stefan, Schäbitz Wolf-Rüdiger, Sommer Clemens
Department of Neuropathology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
Stroke. 2008 Mar;39(3):1012-21. doi: 10.1161/STROKEAHA.107.495069. Epub 2008 Jan 31.
Both application of neurotrophic factors like brain-derived neurotrophic factor (BDNF) and constraint-induced movement therapy like forced arm use have been shown to potentially improve outcome after stroke. The aim of the present study was to check whether postischemic long-term outcome correlates to specific modifications in the abundance of various neurotransmitter receptors.
Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to various treatment groups (n=5 each) with end points at 3 and 6 weeks: (1) ischemic control (saline); (2) BDNF (ischemia, 20 microg BDNF); (3) forced arm use (ischemia, saline, and ipsilateral plaster cast for 5 or 14 days for the 3- and 6-week groups, respectively); and (4) combined treatment (combi; ischemia, 20 microg BDNF, forced arm use). Animals received intravenous bolus infusions of saline or BDNF 1 hour 3 and 5 days after ischemia, respectively. A group of sham rats (n=2) served as a control. A battery of behavioral tests was performed before and up to 6 weeks after ischemia. Quantitative in vitro receptor autoradiography was performed on 12-microm-thick cryostat sections using [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors, respectively.
Best functional outcome was seen after BDNF treatment, whereas vice versa rats with forced arm use did worse in behavioral performance. Improved behavioral outcome was associated with increased perilesional binding densities of NMDA and AMPA receptors 3 weeks after stroke.
Our findings suggest that transient enhanced neurotransmission as reflected by increased ligand binding of NMDA and AMPA receptors may participate in successful postlesional reorganization processes.
脑源性神经营养因子（BDNF）等神经营养因子的应用以及强制使用上肢等强制性诱导运动疗法已被证明可能改善中风后的预后。本研究的目的是检查缺血后长期预后是否与各种神经递质受体丰度的特定改变相关。
成年雄性Wistar大鼠接受光血栓性缺血，并分为不同的治疗组（每组n = 5），终点分别为3周和6周：（1）缺血对照组（生理盐水）；（2）BDNF组（缺血，20微克BDNF）；（3）强制使用上肢组（缺血，生理盐水，3周组和6周组分别使用同侧石膏固定5天和14天）；（4）联合治疗组（联合组；缺血，20微克BDNF，强制使用上肢）。动物在缺血后第3天和第5天分别于1小时接受生理盐水或BDNF静脉推注。一组假手术大鼠（n = 2）作为对照。在缺血前和缺血后长达6周进行一系列行为测试。使用[³H]MK - 801、[³H]AMPA和[³H]蝇蕈醇分别对12微米厚的低温恒温器切片进行定量体外受体放射自显影，以标记NMDA、AMPA和GABAA受体。
BDNF治疗后功能预后最佳，而强制使用上肢的大鼠行为表现较差。行为预后改善与中风后3周时损伤周围NMDA和AMPA受体结合密度增加有关。
我们的研究结果表明，NMDA和AMPA受体配体结合增加所反映的短暂神经传递增强可能参与损伤后成功的重组过程。
