Department of Neurology, University California San Francisco, 675 Nelson Rising Lane, San Francisco, CA, 94158-0663, USA.
Transl Stroke Res. 2024 Feb;15(1):69-86. doi: 10.1007/s12975-022-01111-7. Epub 2023 Jan 27.
Injuries in the developing brain cause significant long-term neurological deficits. Emerging clinical and preclinical data have demonstrated that the pathophysiology of neonatal and childhood stroke share similar mechanisms that regulate brain damage, but also have distinct molecular signatures and cellular pathways. The focus of this review is on two different diseases-neonatal and childhood stroke-with emphasis on similarities and distinctions identified thus far in rodent models of these diseases. This includes the susceptibility of distinct cell types to brain injury with particular emphasis on the role of resident and peripheral immune populations in modulating stroke outcome. Furthermore, we discuss some of the most recent and relevant findings in relation to the immune-neurovascular crosstalk and how the influence of inflammatory mediators is dependent on specific brain maturation stages. Finally, we comment on the current state of treatments geared toward inducing neuroprotection and promoting brain repair after injury and highlight that future prophylactic and therapeutic strategies for stroke should be age-specific and consider gender differences in order to achieve optimal translational success.
发育中的大脑损伤会导致严重的长期神经功能缺陷。新出现的临床和临床前数据表明,新生儿和儿童中风的病理生理学具有相似的调节脑损伤的机制,但也具有不同的分子特征和细胞途径。本综述的重点是两种不同的疾病——新生儿和儿童中风,强调迄今为止在这些疾病的啮齿动物模型中发现的相似点和区别。这包括不同细胞类型对脑损伤的易感性,特别强调常驻和外周免疫细胞在调节中风结果中的作用。此外,我们还讨论了一些与免疫-神经血管相互作用有关的最新和相关发现,以及炎症介质的影响如何取决于特定的大脑成熟阶段。最后,我们对目前针对损伤后诱导神经保护和促进脑修复的治疗方法进行了评论,并强调针对中风的未来预防和治疗策略应该是针对特定年龄的,并考虑到性别差异,以实现最佳的转化成功。