Coupland Kirsten G, Amell Merce Fuentes, Spratt Neil J
School of Biomedical Sciences and Pharmacy, The University of Newcastle Australia, Newcastle, Australia.
Heart and Stroke Program, Hunter Medical Research Institute, Newcastle, Australia.
Fluids Barriers CNS. 2025 Jun 18;22(1):60. doi: 10.1186/s12987-025-00671-8.
Cerebrospinal fluid and interstitial fluid dynamics are critical for maintaining homeostasis in the central nervous system. These fluids facilitate waste clearance, micronutrient distribution, and provide a tightly regulated ionic environment. Ischaemic stroke, a leading cause of morbidity and mortality, disrupts this delicate system, compounding the physiological challenges posed by the condition. Despite recent advances in our understanding of the importance of cerebrospinal fluid (CSF) and interstitial fluid (ISF) movement and exchange, the role of this system in stroke pathophysiology remains underexplored.
Emerging evidence indicates that ischaemic stroke acutely alters CSF and ISF movement and exchange, with effects observed at both local and brain-wide levels. In the hyper-acute phase, there is an influx of CSF into perivascular spaces, potentially contributing to early cell swelling. Over time, impaired clearance mechanisms exacerbate ionic and vasogenic oedema, elevating intracranial pressure and further compromising perfusion in the ischaemic penumbra. Mechanistic studies suggest that disruptions in arterial pulsatility, extracellular space microstructure, and aquaporin 4 localisation may underlie these changes. Experimental models have revealed decreased CSF and ISF exchange, movement and outflow in the hours to days following stroke, with implications for waste clearance and secondary injury processes. The interplay between these dynamics and cortical spreading depolarisations, stroke severity, and cerebrovascular physiology adds complexity to understanding the condition's progression.
The disruption of CSF and ISF movement and exchange may represent a significant, yet underappreciated contributor to post-stroke pathology. Addressing these alterations could offer novel therapeutic avenues to mitigate secondary damage, improve central nervous system (CNS) homeostasis, and enhance recovery outcomes. Future research must focus on elucidating the precise mechanisms of CSF and ISF movement and exchange disturbance and exploring targeted interventions to restore normal fluid dynamics in the CNS post-stroke.
脑脊液和组织间液动力学对于维持中枢神经系统的内环境稳定至关重要。这些液体有助于废物清除、微量营养素分布，并提供严格调控的离子环境。缺血性中风是发病和死亡的主要原因，它破坏了这个微妙的系统，加剧了该病症所带来的生理挑战。尽管我们最近对脑脊液（CSF）和组织间液（ISF）的流动和交换的重要性有了更深入的了解，但该系统在中风病理生理学中的作用仍未得到充分探索。
新出现的证据表明，缺血性中风会急性改变脑脊液和组织间液的流动和交换，在局部和全脑水平均有观察到相关影响。在超急性期，脑脊液会流入血管周围间隙，这可能导致早期细胞肿胀。随着时间的推移，清除机制受损会加剧离子性和血管源性水肿，升高颅内压，并进一步损害缺血半暗带的灌注。机制研究表明，动脉搏动性、细胞外间隙微观结构和水通道蛋白4定位的破坏可能是这些变化的基础。实验模型显示，中风后数小时至数天内，脑脊液和组织间液的交换、流动和流出减少，这对废物清除和继发性损伤过程有影响。这些动力学与皮质扩散去极化、中风严重程度和脑血管生理学之间的相互作用，增加了理解该病症进展的复杂性。
脑脊液和组织间液流动及交换的破坏可能是中风后病理变化的一个重要但未被充分认识的因素。解决这些改变可能会提供新的治疗途径，以减轻继发性损伤、改善中枢神经系统（CNS）的内环境稳定并提高恢复效果。未来的研究必须专注于阐明脑脊液和组织间液流动及交换紊乱的精确机制，并探索有针对性的干预措施，以恢复中风后中枢神经系统的正常液体动力学。
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