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Review
. 2022 Apr 1;19(1):28.
doi: 10.1186/s12987-022-00324-0.

Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review

Katherine G Holste  1 , Fan Xia  2   3 , Fenghui Ye  2 , Richard F Keep  2 , Guohua Xi  4   5
Affiliations
Review

Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review

Katherine G Holste et al. Fluids Barriers CNS. .

Abstract

Intraventricular hemorrhage (IVH) is a significant cause of morbidity and mortality in both neonatal and adult populations. IVH not only causes immediate damage to surrounding structures by way of mass effect and elevated intracranial pressure; the subsequent inflammation causes additional brain injury and edema. Of those neonates who experience severe IVH, 25-30% will go on to develop post-hemorrhagic hydrocephalus (PHH). PHH places neonates and adults at risk for white matter injury, seizures, and death. Unfortunately, the molecular determinants of PHH are not well understood. Within the past decade an emphasis has been placed on neuroinflammation in IVH and PHH. More information has come to light regarding inflammation-induced fibrosis and cerebrospinal fluid hypersecretion in response to IVH. The aim of this review is to discuss the role of neuroinflammation involving clot-derived neuroinflammatory factors including hemoglobin/iron, peroxiredoxin-2 and thrombin, as well as macrophages/microglia, cytokines and complement in the development of PHH. Understanding the mechanisms of neuroinflammation after IVH may highlight potential novel therapeutic targets for PHH.

Keywords: Complement; Intraventricular hemorrhage; Macrophages; Microglia; Neuroinflammation; Posthemorrhagic hydrocephalus.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The imbalance of CSF production/drainage induces hydrocephalus. AfterIVH, CSF drainage is impaired due to inflammation at the leptomeninges and likely causes changes in brain pulsatility.. CSF hypersecretion mainly occurs at the choroid plexus with possible blood-CSF barrier disruption and AQPs upregulation. IVH, intraventricular hemorrhage; CSF, cerebrospinal fluid; AQPs, aquaporins
Fig. 2
Fig. 2
Blood components release triggers neuroinflammation and contributes to subsequent hydrocephalus. Hemoglobin and its primary metabolite iron, peroxiredoxin 2, and thrombin can induce hydrocephalus via pro-inflammatory activated macrophages (red CD68 + cells)/resident microglia (blue CD68 + cells), epiplexus cells (OX6 +), and granulocytes (MPO +).. Blocking blood components’ activity curtails neuroinflammation and alleviates post-hemorrhagic hydrocephalus. Estrogen can exacerbate thrombin-mediated brain injury and aggravate hydrocephalus. HO-1/2, heme oxygenase; LCN2, lipocalin-2; MPO, myeloperoxidase; IBA-1, ionized calcium binding adaptor molecule 1; OX-6, major histocompatibility complex II expressed by epiplexus cells; Prx2, peroxiredoxin 2; PAR-1, protease-activated receptor-1; SCH79797, 3-N-cyclopropyl-7-[(4-propan-2-ylphenyl)methyl]pyrrolo[3,2-f]quinazoline-1,3-diamine;dihydrochloride
Fig. 3
Fig. 3
Kolmer’s epiplexus cells and stromal macrophages hold a crucial role in post-hemorrhagic hydrocephalus genesis. Activation and upregulation of epiplexus cells and stromal macrophages contribute to neuroinflammation and hydrocephalus. Moreover, stromal resident macrophages tend to move to the choroid plexus apical surface after injury stimulation
See this image and copyright information in PMC

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