Neonatal subarachnoid hemorrhage disrupts multiple aspects of cerebellar development.
Neonatal subarachnoid hemorrhage disrupts multiple aspects of cerebellar development.
复制标题
DOI：
10.3389/fnmol.2023.1161086
复制
发表时间：
2023
影响因子：
4.8
通讯作者：
Millen, Kathleen J.
中科院分区：
文献类型：
--
作者：
Butler, David F.;Skibo, Jonathan;Traudt, Christopher M.;Millen, Kathleen J.
关键词：
在过去的十年中，极低胎龄儿(28周妊娠)的存活率有了显著的提高。不幸的是，相当大比例的艾尔干人将遭受神经发育障碍的困扰。小脑出血损伤(CHI)在埃尔干人群中已被越来越多地认识到，并可能导致神经功能障碍；然而，其潜在的机制尚不清楚。为了解决这一认识上的差距，我们开发了一种新的新生小鼠孤立性后颅窝蛛网膜下腔出血(SAH)模型，并研究了急性和长期影响。出生后第6天(P6)SAH后，我们发现P8时外颗粒层(EGL)的增殖水平显著降低，EGL变薄，浦肯野细胞(PC)密度降低，Bergmann胶质(BG)纤维交叉增加。在P42，CHI导致PC密度降低，分子层中间神经元(MLI)密度降低，BG纤维交叉增加。旋转筛查和倒置筛查的结果都没有显示对P35-38的运动强度或学习有显著影响。抗炎药酮洛芬的治疗没有显著改变我们在CHI后的研究结果，这表明对于CHI后的神经炎症的治疗并不能提供显著的神经保护。需要进一步的研究来充分阐明CHI扰乱小脑发育编程的机制，以便开发针对Elgans神经保护的治疗策略。
Over the past decade, survival rates for extremely low gestational age neonates (ELGANs; <28 weeks gestation) has markedly improved. Unfortunately, a significant proportion of ELGANs will suffer from neurodevelopmental dysfunction. Cerebellar hemorrhagic injury (CHI) has been increasingly recognized in the ELGANs population and may contribute to neurologic dysfunction; however, the underlying mechanisms are poorly understood. To address this gap in knowledge, we developed a novel model of early isolated posterior fossa subarachnoid hemorrhage (SAH) in neonatal mice and investigated both acute and long-term effects. Following SAH on postnatal day 6 (P6), we found significant decreased levels of proliferation with the external granular layer (EGL), thinning of the EGL, decreased Purkinje cell (PC) density, and increased Bergmann glial (BG) fiber crossings at P8. At P42, CHI resulted in decreased PC density, decreased molecular layer interneuron (MLI) density, and increased BG fiber crossings. Results from both Rotarod and inverted screen assays did not demonstrate significant effects on motor strength or learning at P35–38. Treatment with the anti-inflammatory drug Ketoprofen did not significantly alter our findings after CHI, suggesting that treatment of neuro-inflammation does not provide significant neuroprotection post CHI. Further studies are required to fully elucidate the mechanisms through which CHI disrupts cerebellar developmental programming in order to develop therapeutic strategies for neuroprotection in ELGANs.
登录
查看更多内容
影响因子：
4.3
作者：
D'Mello AM;Stoodley CJ
通讯作者：
Stoodley CJ
宫内生长受限通过 JamC/Pard3a 分子途径影响颗粒细胞的径向迁移，从而损害小脑发育。
影响因子：
5.3
作者：
Iskusnykh IY;Fattakhov N;Buddington RK;Chizhikov VV
通讯作者：
Chizhikov VV
影响因子：
11.8
作者：
Fleming JT;He W;Hao C;Ketova T;Pan FC;Wright CC;Litingtung Y;Chiang C
通讯作者：
Chiang C
影响因子：
4.2
作者：
Vinukonda, Govindaiah;Hu, Furong;Upreti, Chirag;Ungvari, Zoltan;Zia, Muhammad T.;Stanton, Patric K.;Ballabh, Praveen
通讯作者：
Ballabh, Praveen
影响因子：
3.3
作者：
Galas L;Bénard M;Lebon A;Komuro Y;Schapman D;Vaudry H;Vaudry D;Komuro H
通讯作者：
Komuro H