Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia
Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia
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DOI：
10.1159/000094876
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发表时间：
2006-01-01
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影响因子：
--
通讯作者：
Urashima, Mitsuyoshi
中科院分区：
文献类型：
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作者：
Abo, Masahiro;Yamauchi, Hideki;Urashima, Mitsuyoshi
我们先前使用局部光化学诱导血栓形成(PIT)和功能磁共振成像的大鼠模型，证明了除了脑梗塞周围区域的同侧感觉运动皮质外，在非损伤的对侧感觉运动皮质中也存在激活区域。使用这个模型，我们接下来应用基因表达谱来筛选在激活区域上调的关键分子。从同侧和对侧感觉运动皮质到局灶性脑梗塞和从假控制皮质提取RNA，并与包含1,322个神经学相关基因的基因表达谱阵列杂交。结果显示，在局灶性脑缺血损伤的同侧和对侧皮质，甘氨酸受体均有上调。为了证明甘氨酸受体上调的临床前意义，神经细胞上甘氨酸受体的内源性拮抗剂犬尿酸被鞘内注射。结果，犬尿酸显著地促进了10天内由焦点凹陷引起的瘫痪的行为恢复(P<；0.0001)，通过光束行走进行评估。这些结果表明，鞘内注射甘氨酸受体拮抗剂可能会促进脑梗塞后急性期的行为恢复。版权所有(C)2006 S.Karger AG，巴塞尔。
We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p < 0.0001), as evaluated with beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.