Minor Neuronal Damage and Recovered Cellular Proliferation in the Hippocampus After Continuous Unilateral Forelimb Restraint in Normal Rats
Minor Neuronal Damage and Recovered Cellular Proliferation in the Hippocampus After Continuous Unilateral Forelimb Restraint in Normal Rats
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DOI：
10.1002/jnr.22566
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发表时间：
2011-03-01
影响因子：
4.2
通讯作者：
Hida, Hideki
中科院分区：
文献类型：
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作者：
Ishida, Akimasa;Ueda, Yoshitomo;Hida, Hideki
约束诱导运动疗法（CIMT）包括约束一个完整的肢体，迫使受影响肢体的主要使用，试图增强使用依赖的可塑性和减少功能障碍。为了研究CIMT强迫停用完整前肢是否会导致肢体功能丧失和脑退行性损伤，我们对对照大鼠和前肢受限大鼠进行楼梯试验和水平阶梯试验，然后用能够检测细微神经元损伤的银染色检测与受限相关的组织学改变。受约束大鼠前肢功能未见明显变化。然而，在大鼠的双侧海马中发现了非典型的弱亲银神经元，这是轻微神经损伤的指标。在皮质、纹状体或脊髓中没有发现这种损伤。对脑室下区（SVZ）和颗粒下区（SGZ）神经发生的研究显示，与对照组相比，受抑制大鼠双侧SGZ区溴脱氧尿苷阳性细胞数量明显减少，但SVZ区没有。这种减少伴随着血管内皮生长因子和胶质源性神经营养因子mRNA表达的减少。然而，去除抑制后，细胞增殖减少，基因表达下降。我们的研究结果表明，强制停用完整的前肢对熟练的前肢功能没有显著影响，但对SGZ的神经发生有轻微影响，这表明可能是由于限制引起的轻度应激。(C) 2010 Wiley-Liss, Inc。
Constraint-induced movement therapy (CIMT) involves the restraint of an intact limb to force the dominant use of an affected limb, in an attempt to enhance use-dependent plasticity and reduce dysfunction. To investigate whether forced disuse of an intact forelimb with CIMT causes a loss of limb function and degenerative damage in the brain, a staircase test and a horizontal ladder test were carried out in control rats and forelimb-restrained rats, and then Argyrophil III silver staining, which is capable of detecting subtle neuronal damage, was used to examine histological alterations associated with restraint. No significant changes in forelimb function were observed in restrained rats. However, atypical weak argyrophilic neurons, an indicator of minor neural damage, were found in the bilateral hippocampus of restrained rats. This damage was not found in the cortex, striatum, or spinal cord. Investigation of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) revealed a clear reduction in the number of bromodeoxyuridine-positive cells in bilateral SGZ, but not in the SVZ, in restrained rats compared with controls. This reduction was accompanied by reduced mRNA expression of vascular endothelial growth factor and glial-derived neurotrophic factor. However, reduced cellular proliferation and decreased gene expression were recovered after the removal of the restraint. Our results suggest that forced disuse of the intact forelimb has no significant effect on skilled forelimb function but has a minor effect on neurogenesis in SGZ, suggesting that mild stress may be caused by the restraint. (C) 2010 Wiley-Liss, Inc.