Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats.

Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats.
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DOI:
10.1177/2633105520968904
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发表时间:
2020
影响因子:
3.6
通讯作者:
Kartje GL
Kartje GL
中科院分区:
其他
文献类型:
--
作者:
Ton ST;Adamczyk NS;Gerling JP;Vaagenes IC;Wu JY;Hsu K;O'Brien TE;Tsai SY;Kartje GL

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创伤性脑损伤是一个重大的公共卫生问题,会导致幸存者严重残疾。脑外伤患者入院时往往是酒精中毒;然而,目前尚不清楚急性中毒如何影响创伤性脑损伤的恢复。我们的研究小组之前已经表明,创伤性脑损伤之前的酗酒会导致精细感觉运动任务的长期损害,这与脑室下区增殖和神经母细胞反应的减少有关。然而,创伤性脑损伤之前的酗酒是否会影响海马齿状回的增殖反应尚不清楚。雄性大鼠在脑外伤前 3 天通过胃管饲法酗酒(3 g/kg/天)。创伤性脑损伤后注射 BrdU 来标记细胞增殖。在创伤性脑损伤后24小时、1周和6周对海马齿状背回BrdU+细胞进行体视定量和免疫荧光共聚焦分析。我们发现,单独的创伤性脑损伤或单独的酗酒都会在 24 小时和 1 周时显着增加齿状回增殖。然而,酗酒和创伤性脑损伤联合治疗导致创伤性脑损伤后 24 小时齿状回增殖减少。在第 6 周的时间点,酗酒总体上减少了 BrdU+ 细胞的数量。此外,与车辆创伤性脑损伤组相比,在酒精性脑损伤的齿状门区发现了更多的 BrdU+ 细胞。这些错误迁移的 BrdU+ 细胞的位置和双标记与肺门异位颗粒细胞一致。这项研究的结果表明,创伤性脑损伤前酗酒会在短期内影响齿状回损伤诱导的增殖反应,并可能长期影响齿状回中新生细胞的分布。
Traumatic brain injury is a significant public health issue that results in serious disability in survivors. Traumatic brain injury patients are often intoxicated with alcohol when admitted to the hospital; however, it is not clear how acute intoxication affects recovery from a traumatic brain injury. Our group has previously shown that binge alcohol prior to traumatic brain injury resulted in long-term impairment in a fine sensorimotor task that was correlated with a decreased proliferative and neuroblast response from the subventricular zone. However, whether binge alcohol prior to traumatic brain injury affects the proliferative response in the hippocampal dentate gyrus is not yet known. Male rats underwent binge alcohol (3 g/kg/day) by gastric gavage for 3 days prior to traumatic brain injury. Cell proliferation was labeled by BrdU injections following traumatic brain injury. Stereological quantification and immunofluorescence confocal analysis of BrdU+ cells in the hippocampal dorsal dentate gyrus was performed at 24 hours, 1 week and 6 weeks post traumatic brain injury. We found that either traumatic brain injury alone or binge alcohol alone significantly increased dentate gyrus proliferation at 24 hours and 1 week. However, a combined binge alcohol and traumatic brain injury regimen resulted in decreased dentate gyrus proliferation at 24 hours post-traumatic brain injury. At the 6 week time point, binge alcohol overall reduced the number of BrdU+ cells. Furthermore, more BrdU+ cells were found in the dentate hilar region of alcohol traumatic brain injury compared to vehicle traumatic brain injury groups. The location and double-labeling of these mismigrated BrdU+ cells was consistent with hilar ectopic granule cells. The results from this study showed that pre-traumatic brain injury binge alcohol impacts the injury-induced proliferative response in the dentate gyrus in the short-term and may affect the distribution of newly generated cells in the dentate gyrus in the long-term.
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