Both MK801 and NBQX reduce the neuronal damage after impact-acceleration brain injury
Both MK801 and NBQX reduce the neuronal damage after impact-acceleration brain injury
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DOI：
10.1089/089771502320914679
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发表时间：
2002-11-01
影响因子：
4.2
通讯作者：
Kobayashi, H
中科院分区：
文献类型：
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作者：
Goda, M;Isono, M;Kobayashi, H
为了解弥漫性轴索损伤的发病机制，我们用荧光素(FJ)染色方法研究了大鼠撞击-加速损伤后神经元变性的时空分布。采用Marmarou等人的方法建立Wistar大鼠撞击加速损伤模型。做了一些修改。分别于伤后1、2、7、14、28天处死动物。石蜡包埋冠状切片进行HE或FJ染色，或进行GFAP或淀粉样前体蛋白(APP)免疫组织化学分析。损伤后1~2d，FJ阳性变性神经元主要出现在脑干背侧和丘脑，并与GFAP表达有关。7d后FJ阳性细胞很少。在所有大鼠中，APP主要在扣带、脑脚和桥髓交界处有明显表达。FJ还对这些受损的轴突进行了染色。鞘内分别给予NMDA和AMPA/激动酸受体拮抗剂MK-801和NBQX均可减轻神经元损伤。NBQX对轴突损伤的治疗作用优于MK-801。这些观察结果表明，在这种撞击-加速损伤模型中，不仅发生了轴突损伤，而且还发生了初级神经元损伤。提示NBQX既可直接作用于神经细胞，又可直接作用于白质，NMDA不仅对神经元有明显的保护作用，而且对轴突损伤也有明显的保护作用。
To understand the pathogenesis of diffuse axonal injury, we investigated the temporal and spatial profiles of neuronal degeneration in impact-acceleration injury in rats using Fluoro-Jade (FJ) staining. Impact-acceleration injury was produced in Wistar rats by the method described by Marmarou et al. with some modifications. Animals were sacrificed 1, 2, 7, 14, or 28 days after injury. Paraffin-embedded coronal sections were stained with HE or FJ, or analyzed immunohistochemically for GFAP or amyloid precursor protein (APP). FJ-positive degenerative neurons were found primarily in the dorsal brainstem and thalamus from 1 to 2 days following injury and these were associated with GFAP expression. However, FJ-positive cells were rarely found after 7 days. In all rats, significant expression of APP was observed primarily in the cingulum, cerebral peduncle and pontomedullary junction. FJ also stained these injured axons. Intrathecal administration of both NMDA and AMPA/kinate glutamate receptor antagonists MK-801 and NBQX, respectively, reduced the neuronal injury. NBQX showed more significant effects on axonal injury than MK-801. These observations indicate that not only axonal damage, but also primary neuronal damage occurs in this impact-acceleration injury model. It is also suggested that NBQX can act both directly on neuronal cells and white matter and that NMDA could have a significant protective effect against not only neuronal, but also axonal injury.