The expression of repulsive guidance molecule a after traumatic brain injury: Time-course changes in gene expression in a murine model of controlled cortical impact
The expression of repulsive guidance molecule a after traumatic brain injury: Time-course changes in gene expression in a murine model of controlled cortical impact
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创伤性脑损伤后排斥性引导分子 a 的表达：受控皮质冲击小鼠模型中基因表达的时程变化
DOI：
10.1097/ta.0000000000003041
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发表时间：
2020
影响因子：
3.4
通讯作者：
Tasaki Osamu
中科院分区：
文献类型：
--
作者：
Uemura Eri;Tajima Goro;Murahashi Shimon;Matsumoto Naoya;Tokunaga Ayako;Miura Miyuki;Murase Takehiko;Ikematsu Kazuya;Tasaki Osamu
方法对成年雄性C57BL/6J小鼠进行控制性皮质冲击。分别于伤后6 h、1、3、7、14、21 d取脑组织（每组n= 6）。通过定量聚合酶链反应评估RGMa及其受体neogenin信使RNA （mRNA）在皮层和对侧皮层受损区域的表达变化，并测量炎症相关分子的表达。神经功能缺损也通过柱体试验进行评估。结果在整个实验期间，创伤性脑损伤组的神经学评分均低于假手术组。在第1天，代表性炎症细胞因子TNF-α和趋化因子受体CCR2的mRNA表达在损伤皮质中显著升高，并随着时间的推移逐渐降低，但至少在第14天之前保持较高水平。RGMa和neogenin的mRNA表达在损伤皮质中被显著抑制，直至第3天。有趣的是，RGMa的表达在第1天被抑制，并随着时间的推移而恢复。结论创伤性脑损伤急性期，损伤区炎症环境中炎症因子基因表达显著升高，RGMa和neogenin基因表达显著降低。尽管随后炎症缓解，RGMa基因表达在TBI后1周恢复到正常水平。急性脑损伤的内在再生反应可能会受到RGMa表达恢复的阻碍，提示功能性RGMa抑制可能是一种新的、有效的治疗TBI的方法。
METHODSAdult male C57BL/6J mice were subjected to controlled cortical impact. Brains were extracted 6 hours and 1, 3, 7, 14 and 21 days after injury (n= 6 in each group). Changes in the messenger RNA (mRNA) expression of RGMa and its receptor, neogenin, were evaluated by quantitative polymerase chain reaction in the damaged area of the cortex and contralateral cortex, along with expression measurement of inflammation-related molecules. Neurological deficit was also assessed by the cylinder test.RESULTSNeurological score was consistently lower in the TBI group compared to the sham group throughout the experimental period. The mRNA expressions of representative inflammatory cytokine TNF-α and chemokine receptor CCR2 were remarkably increased in the injured cortex on day 1 and gradually decreased over time, although remaining at higher values at least until day 14. The mRNA expressions of RGMa and neogenin were significantly suppressed in the damaged cortex until day 3. Interestingly, RGMa expression was suppressed most on day 1 and recovered over time.CONCLUSIONIn the acute phase of TBI, gene expression of inflammatory cytokines significantly increased, and gene expressions of RGMa and neogenin significantly decreased in the inflammatory milieu of the damaged area. Despite the subsequent remission of inflammation, RGMa gene expression recovered to the normal level 1 week after TBI. Intrinsic regenerative response to acute brain injury might be hampered by the following recovery of RGMa expression, hinting at the possibility of functional RGMa inhibition as a new, effective maneuver against TBI.