Kuptsova Kristina, Kvist Elisabet, Nitzsche Franziska, Jolkkonen Jukka
Institute of Clinical Medicine - Neurology, University of Eastern, Kuopio, Finland;
Rom J Morphol Embryol. 2015;56(1):41-7.
Functional recovery after cerebral ischemia may be enhanced by activation of the noradrenergic system and by environmental enrichment. The underlying mechanisms have remained elusive, but endogenous neurogenesis and perilesional angiogenesis have been speculated to contribute to the behavioral improvement. To address this question, neurogenesis in the subventricular zone (SVZ) and perilesional angiogenesis (RECA-1) were correlated with behavioral performance in forty Wistar rats subjected to transient middle cerebral artery occlusion (MCAO) or sham-operation. Atipamezole, an α2-adrenoreceptor antagonist (1 mg÷kg, i.p.), was administered for 10 days together with housing of rats in an enriched environment. MCAO rats and sham-operated rats housed in single non-enriched cages were used as controls. Histological analysis after 28-day behavioral follow-up showed a massive increase in doublecortin (DCX)-positive cells in the SVZ both in MCAO rats housed in single cages and in the enriched environment together with atipamezole treatment whereas perilesional RECA-1 staining for new blood vessels was not altered. Time to the first contact and time to remove sticky stimuli from the forelimbs indicated improved sensory processing, which disappeared after cessation of atipamezole administration. Skilled forelimb use as measured by performance in Montoya's staircase test was not affected by the treatment. There were no correlations between behavioral measures and histology. Thus, sensory facilitation or reversal of hypometabolism by the combined therapy may be the mechanism accounting for the improved behavior after stroke independent from neurogenesis and angiogenesis.
脑缺血后的功能恢复可通过去甲肾上腺素能系统的激活和环境富集得到增强。其潜在机制尚不清楚，但内源性神经发生和损伤周围血管生成被推测有助于行为改善。为解决这个问题，在40只接受短暂大脑中动脉闭塞（MCAO）或假手术的Wistar大鼠中，将脑室下区（SVZ）的神经发生和损伤周围血管生成（RECA-1）与行为表现相关联。给予阿替美唑，一种α2-肾上腺素能受体拮抗剂（1毫克÷千克，腹腔注射），持续10天，同时将大鼠饲养在富集环境中。将饲养在单个非富集笼中的MCAO大鼠和假手术大鼠作为对照。28天行为随访后的组织学分析显示，在单个笼中饲养的MCAO大鼠以及在富集环境中接受阿替美唑治疗的大鼠中，SVZ中双皮质素（DCX）阳性细胞大量增加，而损伤周围新血管的RECA-1染色未改变。首次接触时间和从前肢去除粘性刺激的时间表明感觉处理得到改善，在停止阿替美唑给药后这种改善消失。通过蒙托亚阶梯试验中的表现衡量的熟练前肢使用不受该治疗影响。行为测量与组织学之间没有相关性。因此，联合治疗引起的感觉促进或代谢减退的逆转可能是中风后行为改善的机制，与神经发生和血管生成无关。
