Schulz Lauren N, Varghese Aaron, Michenkova Marie, Wedemeyer Michelle, Pindrik Jonathan A, Leonard Jeffrey R, Garcia-Bonilla Maria, McAllister James Pat, Cassady Kevin, Wilson Richard K, Mardis Elaine R, Limbrick David D, Isaacs Albert M
Department of Neurological Surgery, Ohio State University Medical Center, Columbus, OH, USA.
Department of Undergraduate Studies, Miami University, Oxford, OH, USA.
Pediatr Res. 2024 Dec 26. doi: 10.1038/s41390-024-03733-z.
Post-hemorrhagic hydrocephalus (PHH) is a severe complication in premature infants following intraventricular hemorrhage (IVH). It is characterized by abnormal cerebrospinal fluid (CSF) accumulation, disrupted CSF dynamics, and elevated intracranial pressure (ICP), leading to significant neurological impairments.
This review provides an overview of recent molecular insights into the pathophysiology of PHH and evaluates emerging therapeutic approaches aimed at addressing its underlying mechanisms.
Recent studies were reviewed, focusing on molecular and cellular mechanisms implicated in PHH, including neuroinflammatory pathways, immune mediators, and regulatory genes. The potential of advanced technologies such as whole genome/exome sequencing, proteomics, epigenetics, and single-cell transcriptomics to identify key molecular targets was also analyzed.
PHH has been strongly linked to neuroinflammatory processes triggered by the degradation of blood byproducts. These processes involve cytokines, chemokines, the complement system, and other immune mediators, as well as regulatory genes and epigenetic mechanisms. Current treatments, primarily surgical CSF diversion, do not address the underlying molecular pathology. Emerging therapies, such as mesenchymal stem cell-based interventions, show promise in modulating immune responses and mitigating neurological damage. However, concerns about the safety of these novel approaches in neonatal populations and their potential effects on brain development remain unresolved.
Advanced molecular tools and emerging therapies have the potential to transform the treatment of PHH by targeting its underlying pathophysiology. Further research is needed to validate these approaches, enhance their safety profiles, and improve outcomes for infants with PHH.
出血后脑积水（PHH）是早产儿脑室内出血（IVH）后的一种严重并发症。其特征为脑脊液（CSF）异常积聚、脑脊液动力学紊乱以及颅内压（ICP）升高，导致严重的神经功能障碍。
本综述概述了近期对PHH病理生理学的分子见解，并评估了旨在解决其潜在机制的新兴治疗方法。
回顾了近期的研究，重点关注与PHH相关的分子和细胞机制，包括神经炎症途径、免疫介质和调控基因。还分析了全基因组/外显子组测序、蛋白质组学、表观遗传学和单细胞转录组学等先进技术在识别关键分子靶点方面的潜力。
PHH与血液副产物降解引发的神经炎症过程密切相关。这些过程涉及细胞因子、趋化因子、补体系统和其他免疫介质，以及调控基因和表观遗传机制。目前的治疗方法主要是手术性脑脊液分流，无法解决潜在的分子病理学问题。新兴疗法，如基于间充质干细胞的干预措施，在调节免疫反应和减轻神经损伤方面显示出前景。然而，这些新方法在新生儿群体中的安全性及其对脑发育的潜在影响仍未得到解决。
先进的分子工具和新兴疗法有可能通过针对其潜在的病理生理学来改变PHH的治疗。需要进一步研究来验证这些方法，提高其安全性，并改善PHH婴儿的治疗效果。
