Tumor necrosis factor-a attenuates N-methyl-D-aspartate-mediated neurotoxicity in neonatal rat hippocampus.
Tumor necrosis factor-a attenuates N-methyl-D-aspartate-mediated neurotoxicity in neonatal rat hippocampus.
复制标题
肿瘤坏死因子-a 可减轻新生大鼠海马中 N-甲基-D-天冬氨酸介导的神经毒性。
DOI：
10.1016/s0006-8993(99)02126-5
复制
发表时间：
1999
期刊：
影响因子：
2.9
通讯作者：
Barks,JD
中科院分区：
文献类型：
--
作者：
Liu,XH;Xu,H;Barks,JD
肿瘤坏死因子-α(肿瘤坏死因子-α)参与了新生儿急性脑损伤的病理生理过程。我们假设急性脑损伤会诱导肿瘤坏死因子α的表达，外源性肿瘤坏死因子α会影响N-甲基-D-天冬氨酸诱导的组织损伤的严重程度。我们进行了两组互补的实验，以评估肿瘤坏死因子α在脑内注射N-甲基-D-天冬氨酸所致的兴奋性毒性损伤新生啮齿动物模型中的潜在作用(S)。应用免疫组织化学和ELISA法检测N-甲基-D-天冬氨酸诱导的肿瘤坏死因子α表达的变化，并与N-甲基-D-天冬氨酸联合注射，评价该细胞因子对组织损伤程度的影响。海马区和纹状体内注射N-甲基-D-天冬氨酸(5nmol)均可刺激肿瘤坏死因子α的表达。损毁后3~12h，肿瘤坏死因子α表达增强，表达增强，主要分布于痂体内的神经胶质细胞和同侧海马、纹状体、皮质、丘脑的中间神经元细胞。单独在海马区或纹状体内注射肿瘤坏死因子α(50 Ng)不会引起神经病理损伤。在海马区，当联合注射N-甲基-D-天冬氨酸(5或10nmol)时，肿瘤坏死因子α(50 Ng)可减轻兴奋性毒性损伤，与热处理的肿瘤坏死因子α联合注射的对照组相比，减轻35%-57%。相反，在纹状体，联合注射肿瘤坏死因子α和N-甲基-D-天冬氨酸对随后的损害的严重程度没有影响。结果表明，新生大鼠脑内兴奋性损伤后，神经胶质细胞和神经元中迅速产生肿瘤坏死因子α，外源性肿瘤坏死因子α可导致兴奋性毒性损伤的区域特异性减弱。我们推测，内源性肿瘤坏死因子α可能调节发育中脑组织对兴奋性毒性损伤的反应。
Tumor necrosis factor-α (TNFα) has been implicated in the pathophysiology of acute neonatal brain injury. We hypothesized that acute brain injury would induce TNFα expression and that exogenous TNFα would influence the severity of N-methyl-d-aspartate-induced tissue damage. We performed two complementary groups of experiments to evaluate the potential role(s) of TNFα in a neonatal rodent model of excitotoxic injury, elicited by intracerebral injection of N-methyl-d-aspartate. We used immunohistochemistry and ELISA to evaluate N-methyl-d-aspartate-induced changes in TNFα expression, and we co-injected TNFα with N-methyl-d-aspartate, to evaluate the effect of this cytokine on the severity of tissue injury. Both intra-hippocampal and intra-striatal injection of N-methyl-d-aspartate (5 nmol) stimulated TNFα expression. Increased TNFα expression was detected 3–12 h after lesioning; TNFα was localized both in glial cells in the corpus callosum, and in cells with the morphology of interneurons in the ipsilateral hippocampus, striatum, cortex and thalamus. Intra-hippocampal or intra-striatal administration of TNFα (50 ng) alone did not elicit neuropathologic damage. In the hippocampus, when co-injected with N-methyl-d-aspartate (5 or 10 nmol), TNFα (50 ng) attenuated excitotoxic injury by 35%–57%, compared to controls co-injected with heat-treated TNFα. In contrast, in the striatum, co-injection of TNFα with N-methyl-d-aspartate had no effect on the severity of the ensuing damage. The data indicate that TNFα is rapidly produced in glial cells and neurons after an excitotoxic insult in the neonatal rat brain, and that administration of exogenous TNFα results in region-specific attenuation of excitotoxic damage. We speculate that endogenous TNFα may modulate the tissue response to excitotoxic injury in the developing brain.