Bosche Bert, Mergenthaler Philipp, Doeppner Thorsten R, Hescheler Jürgen, Molcanyi Marek
Department of Neurocritical Care, Neurological and Neurosurgical First Stage Rehabilitation and Weaning, MediClin Klinik Reichshof, Berglandstr.1, 51580, Reichshof-Eckenhagen, Germany.
Faculty of Medicine, Department of Neurology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Transl Stroke Res. 2020 Jun;11(3):337-344. doi: 10.1007/s12975-019-00735-6. Epub 2019 Sep 14.
Intracerebral hemorrhage in combination with intraventricular hemorrhage (IVH) is a severe type of stroke frequently leading to prolonged clinical care, continuous disability, shunt dependency, and high mortality. The molecular mechanisms induced by IVH are complex and not fully understood. Moreover, the treatment options for IVH are limited. Intraventricular recombinant tissue plasminogen activator (rt-PA) dissolves the blood clot in the ventricular system; however, whether the clinical outcome is thereby positively affected is still being debated. The mechanistic cascade induced by intraventricular rt-PA therapy may cure and harm in parallel. Despite the fact that intraventricular blood clots are thereby dissolved, blood derivatives enter the parenchyma and may still adversely affect functional structures of the brain: Smaller blood clots may obstruct the perivascular (Virchow-Robin) space and thereby the glymphatic system with detrimental consequences for cerebrospinal fluid (CSF)/interstitial fluid (ISF) flow. These clots, blood cells but also blood derivatives in the perivascular space, destabilize the blood-brain barrier from the brain parenchyma side, thereby also functionally weakening the neurovascular unit. This may lead to further accommodation of serum proteins in the ISF and particularly in the perivascular space further contributing to the adverse effects on the neuronal microenvironment. Finally, the arterial (Pacchionian) granulations have to cope with ISF containing this "blood, cell, and protein cocktail," resulting in obstruction and insufficient function of the arterial granulations, followed by a malresorptive hydrocephalus. Particularly in light of currently improved knowledge on the physiologic and pathophysiologic clearance of cerebrospinal fluid and interstitial fluid, a critical discussion and reevaluation of our current therapeutic strategies to treat intraventricular hemorrhages are needed to successfully treat patients suffering from this severe type of stroke. In this review, we therefore summarize and discuss recent clinical trials and future directions for the field of IVH with respect to the currently increased understanding of the glymphatic system and the neurovascular unit pathophysiology.
脑内出血合并脑室出血（IVH）是一种严重的中风类型，常导致临床护理时间延长、持续性残疾、依赖分流以及高死亡率。IVH引发的分子机制复杂，尚未完全明确。此外，IVH的治疗选择有限。脑室内重组组织型纤溶酶原激活剂（rt-PA）可溶解脑室系统中的血凝块；然而，其是否能对临床结局产生积极影响仍存在争议。脑室内rt-PA治疗引发的机制级联反应可能在治疗的同时造成损害。尽管脑室内血凝块因此被溶解，但血液衍生物进入脑实质，仍可能对脑的功能结构产生不利影响：较小的血凝块可能阻塞血管周围（维氏-罗宾）间隙，进而阻碍类淋巴系统，对脑脊液（CSF）/组织间液（ISF）流动产生有害影响。这些血凝块、血细胞以及血管周围间隙中的血液衍生物，会从脑实质侧破坏血脑屏障的稳定性，从而在功能上削弱神经血管单元。这可能导致血清蛋白在ISF中进一步蓄积，尤其是在血管周围间隙，进一步加重对神经元微环境的不利影响。最后，蛛网膜颗粒不得不应对含有这种“血液、细胞和蛋白质混合物”的ISF，导致蛛网膜颗粒阻塞和功能不足，继而引发吸收不良性脑积水。鉴于目前对脑脊液和组织间液生理及病理生理清除的认识有所提高，尤其需要对我们目前治疗脑室出血的治疗策略进行批判性讨论和重新评估，以成功治疗患有这种严重中风类型的患者。因此，在本综述中，我们总结并讨论了IVH领域最近的临床试验以及未来方向，这是基于目前对类淋巴系统和神经血管单元病理生理学的更多理解。
