Bolton S J, Perry V H
Department of Pharmacology, University of Oxford, United Kingdom.
Exp Neurol. 1998 Nov;154(1):231-40. doi: 10.1006/exnr.1998.6927.
Acute neuronal degeneration can be induced by intracerebral injections of the glutamate receptor agonists kainic acid (KA) and NMDA (N-methyl-D-aspartate). It is accompanied by an inflammatory response that has not yet been fully investigated. We have previously demonstrated that the juvenile rat brain is more susceptible to an inflammatory challenge when compared to adult rat brain. This study set out to investigate whether this also applied to the inflammatory response associated with acute neuronal degeneration. NMDA and kainic acid were injected into the rat striatum and lesion size, leucocyte recruitment, and blood-brain barrier (BBB) breakdown were assessed after 4, 8, 12, 24, 72, and 168 h. Both NMDA and KA induced lesions of similar volume at either age and apoptotic and necrotic nuclei could be detected. NMDA induced cellular loss by 4 h, whereas KA-injected rats did not show signs of neuronal loss until 8-12 h. The inflammatory response was characterized by an infiltration of neutrophils followed by macrophages. Juvenile rats showed a greater susceptibility to leucocyte recruitment compared to adult rats. BBB breakdown in response to NMDA injection occurred in the absence of cellular recruitment at 4 h in juveniles and was significantly greater in juvenile compared to adult rats at 8 h. BBB breakdown was minimal in KA-injected animals while at 7 days an influx of serum IgG coincided with a loss of astrocytic GFAP staining within the lesion.
脑室内注射谷氨酸受体激动剂 kainic 酸（KA）和 NMDA（N-甲基-D-天冬氨酸）可诱导急性神经元变性。其伴随着一种尚未得到充分研究的炎症反应。我们之前已经证明，与成年大鼠脑相比，幼年大鼠脑对炎症刺激更敏感。本研究旨在调查这是否也适用于与急性神经元变性相关的炎症反应。将 NMDA 和 kainic 酸注入大鼠纹状体，并在 4、8、12、24、72 和 168 小时后评估损伤大小、白细胞募集和血脑屏障（BBB）破坏情况。在两个年龄段，NMDA 和 KA 均诱导出相似体积的损伤，并且可以检测到凋亡和坏死的细胞核。NMDA 在 4 小时时诱导细胞丢失，而注射 KA 的大鼠直到 8 - 12 小时才显示出神经元丢失的迹象。炎症反应的特征是中性粒细胞随后是巨噬细胞的浸润。与成年大鼠相比，幼年大鼠对白细胞募集表现出更高的易感性。幼年大鼠在 4 小时时对 NMDA 注射的血脑屏障破坏在没有细胞募集的情况下发生，并且在 8 小时时幼年大鼠的血脑屏障破坏比成年大鼠明显更大。注射 KA 的动物血脑屏障破坏最小，而在 7 天时血清 IgG 的流入与损伤内星形胶质细胞 GFAP 染色的丧失同时发生。
