当前位置: X-MOL 学术J. Neurotrauma › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Mice Born to Mothers with Gravida Traumatic Brain Injury Have Distorted Brain Circuitry and Altered Immune Responses
Journal of Neurotrauma ( IF 4.2 ) Pub Date : 2021-10-12 , DOI: 10.1089/neu.2021.0048
Maha Saber 1, 2 , J Bryce Ortiz 1, 2, 3 , Luisa M Rojas Valencia 1, 2, 3 , Xiaokuang Ma 4 , Bret R Tallent 1, 2, 3 , P David Adelson 1, 2 , Rachel K Rowe 1, 2, 3 , Shenfeng Qiu 4 , Jonathan Lifshitz 1, 2, 3
Affiliation  

Intimate partner violence (IPV) increases risk of traumatic brain injury (TBI). Physical assaults increase in frequency and intensity during pregnancy. The consequences of TBI during pregnancy (gravida TBI; gTBI) on offspring development is unknown, for which stress and inflammation during pregnancy worsen fetal developmental outcomes. We hypothesized that gTBI would lead to increased anxiety- and depression-related behavior, altered inflammatory responses and gut pathology, and distorted brain circuitry in mixed-sex offspring compared to mice born to control mothers. Pregnant dams received either diffuse TBI or sham injury (control) 12 days post-coitum. We found that male gTBI offspring were principal drivers of the gTBI effects on health, physiology, and behavior. For example, male, but not female, gTBI offspring weighed significantly less at weaning compared to male control offspring. At post-natal day (PND) 28, gTBI offspring had significantly weaker intralaminar connectivity onto layer 5 pre-frontal pyramidal neurons compared to control offspring. Neurological performance on anxiety-like behaviors was decreased, with only marginal differences in depressive-like behaviors, for gTBI offspring compared to control offspring. At PND42 and PND58, circulating neutrophil and monocyte populations were significantly smaller in gTBI male offspring than control male offspring. In response to a subsequent inflammatory challenge at PND75, gTBI offspring had significantly smaller circulating neutrophil populations than control offspring. Anxiety-like behaviors persisted during the immune challenge in gTBI offspring. However, spleen immune response and gut histology showed no significant differences between groups. The results compel further studies to determine the full extent of gTBI on fetal and maternal outcomes.

中文翻译:

患有妊娠创伤性脑损伤的母亲所生的小鼠大脑回路扭曲并改变了免疫反应

亲密伴侣暴力 (IPV) 会增加创伤性脑损伤 (TBI) 的风险。怀孕期间身体攻击的频率和强度都会增加。妊娠期间 TBI(妊娠 TBI;gTBI)对后代发育的影响尚不清楚,妊娠期间的压力和炎症会恶化胎儿的发育结果。我们假设,与对照母亲所生的小鼠相比,gTBI 会导致混性别后代的焦虑和抑郁相关行为增加,炎症反应和肠道病理改变,以及大脑回路扭曲。怀孕母鼠在交配后 12 天受到弥漫性 TBI 或假伤害(对照)。我们发现男性 gTBI 后代是 gTBI 对健康、生理和行为影响的主要驱动因素。例如,与雄性对照后代相比,雄性(而非雌性)gTBI 后代在断奶时的体重显着减轻。在出生后第 28 天 (PND),与对照后代相比,gTBI 后代与第 5 层前额叶锥体神经元的层内连接明显较弱。与对照后代相比,gTBI 后代的焦虑样行为神经学表现有所下降,抑郁样行为仅存在微小差异。在 PND42 和 PND58 时,gTBI 雄性后代的循环中性粒细胞和单核细胞数量显着小于对照雄性后代。为了应对 PND75 随后的炎症挑战,gTBI 后代的循环中性粒细胞数量明显少于对照后代。gTBI 后代在免疫挑战期间持续存在类似焦虑的行为。然而,脾脏免疫反应和肠道组织学显示各组之间没有显着差异。这些结果需要进一步的研究来确定 gTBI 对胎儿和母亲结局的全面影响。
更新日期:2021-10-13
down
wechat
bug