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中风后兴奋性-抑制性平衡的年龄依赖性。

Age dependence of excitatory-inhibitory balance following stroke.

机构信息

Department of Neurology, Friedrich Schiller University, Jena, Germany.

出版信息

Neurobiol Aging. 2012 Jul;33(7):1356-63. doi: 10.1016/j.neurobiolaging.2010.11.019. Epub 2011 Jan 22.

DOI:10.1016/j.neurobiolaging.2010.11.019
PMID:21257232
Abstract

The mechanisms which mediate cortical map plasticity and functional recovery following stroke remain a matter of debate. Readjustment of the excitatory-inhibitory balance may support cortical map plasticity in perilesional areas. Here we studied cortical net inhibition in the vicinity of photothrombotically-induced cortical lesions in young adult (3 months) and aged (24 months) male rats. Field potentials were recorded in cortical layer II/III following application of paired-pulse stimulation at layer VI/white matter in coronal brain slices. Additionally, we analyzed the regional distribution of 5 major gamma-aminobutyric acid A (GABA(A)) receptor subunits (α1, α2, α3, α5, and γ2) by immunohistochemistry. Paired-pulse inhibition in the perilesional parietal cortex was decreased in young rats but was increased in aged rats. As a consequence of the diminished intrinsic net inhibition in aged control animals, the excitatory-inhibitory balance was readjusted to an age-independent similar level in young and aged lesioned rats in a homeostatic-like fashion. These physiological changes in neuronal activity were accompanied by age-specific laminar alterations of the gamma-aminobutyric acid A (GABA(A)) receptor subunit composition, most prominently of the subunit α5. The present study suggests that the mechanisms underlying functional reorganization in aged animals may be distinctly different from those in young animals.

摘要

皮层图可塑性和中风后功能恢复的调节机制仍然存在争议。兴奋性-抑制性平衡的调整可能支持病变周围区域的皮层图可塑性。在这里,我们研究了光血栓诱导的皮层损伤附近年轻成年(3 个月)和老年(24 个月)雄性大鼠皮层的净抑制。在冠状脑切片的皮层层 II/III 中记录了在皮层层 VI/白质施加成对脉冲刺激后的场电位。此外,我们通过免疫组织化学分析了 5 种主要γ-氨基丁酸 A(GABA(A))受体亚基(α1、α2、α3、α5 和 γ2)的区域分布。病变周围顶叶皮层的成对脉冲抑制在年轻大鼠中降低,但在老年大鼠中增加。由于老年对照组动物内在净抑制的减少,兴奋性-抑制性平衡以一种类似自身平衡的方式在年轻和老年损伤大鼠中重新调整到与年龄无关的相似水平。神经元活动的这些生理变化伴随着γ-氨基丁酸 A(GABA(A))受体亚基组成的特定于年龄的层变化,最明显的是亚基α5。本研究表明,老年动物功能重组的机制可能与年轻动物明显不同。

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