Research progress on the pathogenesis and treatment of hydrocephalus secondary to intraventricular hemorrhage

doi:10.3877/cma.j.issn.2095-9141.2025.03.009

Abstract

Abstract:

Intraventricular hemorrhage (IVH) is a prevalent complication associated with neurological disorders in both premature infants and adults. The presence of bloody cerebrospinal fluid not only induces inflammation and damage to brain tissue but may also lead to the development of post-hemorrhagic hydrocephalus (PHH) in some patients. Once PHH is formed, ventriculoperitoneal shunt surgery is often required, but this surgical intervention carries inherent risks, including blockage, displacement, and infection of the shunt tubes. Currently, clinical and basic research have revealed the pathophysiological mechanisms of IVH-PHH, and explored its potential intervention strategies from a molecular biology perspective. This article mainly reviews the pathogenesis and treatment progress of IVH-PHH, aiming to provide new perspectives and ideas for drug therapy and target selection of this disease.

Key words: Intraventricular hemorrhage, Hydrocephalus, Pathogenesis, Research progress

Shuo Liu, Wenyu Ji, Hu Qin, Yongxin Wang. Research progress on the pathogenesis and treatment of hydrocephalus secondary to intraventricular hemorrhage[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2025, 11(03): 192-196.

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References 53

[1]	Holste KG, Xia F, Ye F, et al. Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review[J]. Fluids Barriers CNS, 2022, 19(1): 28. DOI: 10.1186/s12987-022-00324-0.
[2]	Murphy BP, Inder TE, Rooks V, et al. Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome[J]. Arch Dis Child Fetal Neonatal Ed, 2002, 87(1): F37-F41. DOI: 10.1136/fn.87.1.f37.
[3]	Zhang N, Zhang D, Sun J, et al. Contribution of tumor characteristics and surgery-related factors to symptomatic hydrocephalus after posterior fossa tumor resection: a single-institution experience[J]. J Neurosurg Pediatr, 2023, 31(2): 99-108. DOI: 10.3171/2022.10.Peds22281.
[4]	Chen Z, Zhou M, Wen H, et al. Predictive factors for persistent postoperative hydrocephalus in children undergoing surgical resection of periventricular tumors[J]. Front Neurol, 2023, 14: 1136840. DOI: 10.3389/fneur.2023.1136840.
[5]	Guo ZY, Zhong ZA, Peng P, et al. A scoring system categorizing risk factors to evaluate the need for ventriculoperitoneal shunt in pediatric patients after brain tumor resection[J]. Front Oncol, 2023, 13: 1248553. DOI: 10.3389/fonc.2023.1248553.
[6]	Jabbarli R, Reinhard M, Roelz R, et al. The predictors and clinical impact of intraventricular hemorrhage in patients with aneurysmal subarachnoid hemorrhage[J]. Int J Stroke, 2016, 11(1): 68-76. DOI: 10.1177/1747493015607518.
[7]	Darkwah Oppong M, Gembruch O, Herten A, et al. Intraventricular hemorrhage caused by subarachnoid hemorrhage: does the severity matter?[J]. World Neurosurg, 2018, 111: e693-e702. DOI: 10.1016/j.wneu.2017.12.148.
[8]	Klebe D, McBride D, Krafft PR, et al. Posthemorrhagic hydrocephalus development after germinal matrix hemorrhage: established mechanisms and proposed pathways[J]. J Neurosci Res, 2020, 98(1): 105-120. DOI: 10.1002/jnr.24394.
[9]	Lolansen SD, Rostgaard N, Barbuskaite D, et al. Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters[J]. Fluids Barriers CNS, 2022, 19(1): 62. DOI: 10.1186/s12987-022-00360-w.
[10]	Perlman JM. Periventricular-intraventricular hemorrhage in the premature infant-a historical perspective[J]. Semin Perinatol, 2022, 46(5): 151591. DOI: 10.1016/j.semperi.2022.151591.
[11]	Hunt RJ, Nagaraja TN, Knight R, et al. Deuterium MRI for CSF studies in normal and hydrocephalic rats[J]. Neurosurgery, 2024, 70(Supplement_1): 46-47. DOI: 10.1227/neu.0000000000002809_185.
[12]	Kelley DH. Brain cerebrospinal fluid flow[J]. Phys Rev Fluids, 2021, 6(7): 070501. DOI: 10.1103/physrevfluids.6.070501.
[13]	Wilson CD, Safavi-Abbasi S, Sun H, et al. Meta-analysis and systematic review of risk factors for shunt dependency after aneurysmal subarachnoid hemorrhage[J]. J Neurosurg, 2017, 126(2): 586-595. DOI: 10.3171/2015.11.Jns152094.
[14]	Czorlich P, Ricklefs F, Reitz M, et al. Impact of intraventricular hemorrhage measured by Graeb and LeRoux score on case fatality risk and chronic hydrocephalus in aneurysmal subarachnoid hemorrhage[J]. Acta Neurochir (Wien), 2015, 157(3): 409-415. DOI: 10.1007/s00701-014-2334-z.
[15]	Rasmussen MK, Mestre H, Nedergaard M. Fluid transport in the brain[J]. Physiol Rev, 2022, 102(2): 1025-1151. DOI: 10.1152/physrev.00031.2020.
[16]	Hladky SB, Barrand MA. The glymphatic hypothesis: the theory and the evidence[J]. Fluids Barriers CNS, 2022, 19(1): 9. DOI: 10.1186/s12987-021-00282-z.
[17]	Ladrón-de-Guevara A, Shang JK, Nedergaard M, et al. Perivascular pumping in the mouse brain: improved boundary conditions reconcile theory, simulation, and experiment[J]. J Theor Biol, 2022, 542: 111103. DOI: 10.1016/j.jtbi.2022.111103.
[18]	Tithof J, Boster KAS, Bork PAR, et al. A network model of glymphatic flow under different experimentally-motivated parametric scenarios[J]. iScience, 2022, 25(5): 104258. DOI: 10.1016/j.isci.2022.104258.
[19]	Du T, Mestre H, Kress BT, et al. Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema[J]. Brain, 2022, 145(2): 787-797. DOI: 10.1093/brain/awab293.
[20]	Haldrup M, Rasmussen M, Mohamad N, et al. Intraventricular lavage vs external ventricular drainage for intraventricular hemorrhage: a randomized clinical trial[J]. JAMA Netw Open, 2023, 6(10): e2335247. DOI: 10.1001/jamanetworkopen.2023.35247.
[21]	廖长品,李忠华,李廷阳,等.机器人引导脑室分区穿刺引流术治疗重型脑室内出血研究[J].中华神经医学杂志, 2023, 22(8): 786-793. DOI: 10.3760/cma.j.cn115354-20230411-00225.
[22]	Garavaglia J, Hardigan T, Turner R, et al. Continuous intrathecal medication delivery with the IRRA flow catheter: pearls and early experience[J]. Oper Neurosurg, 2024, 26(3): 293-300. DOI: 10.1227/ons.0000000000000940.
[23]	刁正文,徐愈畅,张杰,等. β-七叶皂苷钠联合甘油果糖治疗脑出血的临床效果分析[J].中华神经创伤外科电子杂志, 2023, 9(1): 32-37. DOI: 10.3877/cma.j.issn.2095-9141.2023.01.006.
[24]	Feng Z, Tan Q, Tang J, et al. Intraventricular administration of urokinase as a novel therapeutic approach for communicating hydrocephalus[J]. Transl Res, 2017, 180: 77-90.e72. DOI: 10.1016/j.trsl.2016.08.004.
[25]	Haldrup M, Miscov R, Mohamad N, et al. Treatment of intraventricular hemorrhage with external ventricular drainage and fibrinolysis: a comprehensive systematic review and meta-analysis of complications and outcome[J]. World Neurosurg, 2023, 174: 183-196.e186. DOI: 10.1016/j.wneu.2023.01.021.
[26]	Hanley DF, Lane K, McBee N, et al. Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR Ⅲ trial[J]. Lancet, 2017, 389(10069): 603-611. DOI: 10.1016/s0140-6736(16)32410-2.
[27]	Carpenter AB, Lara-Reyna J, Hardigan T, et al. Use of emerging technologies to enhance the treatment paradigm for spontaneous intraventricular hemorrhage[J]. Neurosurg Rev, 2022, 45(1): 317-328. DOI: 10.1007/s10143-021-01616-z.
[28]	Gilhus NE, Deuschl G. Neuroinflammation-a common thread in neurological disorders[J]. Nat Rev Neurol, 2019, 15(8): 429-430. DOI: 10.1038/s41582-019-0227-8.
[29]	Karimy JK, Zhang J, Kurland DB, et al. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus[J]. Nat Med, 2017, 23(8): 997-1003. DOI: 10.1038/nm.4361.
[30]	Wang J, Liu R, Hasan MN, et al. Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke[J]. J Neuroinflammation, 2022, 19(1): 91. DOI: 10.1186/s12974-022-02456-4.
[31]	Chaudhry SR, Shafique S, Sajjad S, et al. Janus faced HMGB1 and post-aneurysmal subarachnoid hemorrhage (aSAH) inflammation [J]. Int J Mol Sci, 2022, 23(19): 11216. DOI: 10.3390/ijms231911216.
[32]	Cao Y, Liu C, Li G, et al. Metformin alleviates delayed hydrocephalus after intraventricular hemorrhage by inhibiting inflammation and fibrosis[J]. Transl Stroke Res, 2023, 14(3): 364-382. DOI: 10.1007/s12975-022-01026-3.
[33]	Khan OH, Enno TL, Del Bigio MR. Brain damage in neonatal rats following kaolin induction of hydrocephalus[J]. Exp Neurol, 2006, 200(2): 311-320. DOI: 10.1016/j.expneurol.2006.02.113.
[34]	Garrett MC, Otten ML, Starke RM, et al. Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage[J]. Brain Res, 2009, 1298171-177. DOI: 10.1016/j.brainres.2009.04.047.
[35]	Tang J, Jila S, Luo T, et al. C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats[J]. Neuropharmacology, 2022, 205: 108927. DOI: 10.1016/j.neuropharm.2021.108927.
[36]	Strahle JM, Garton T, Bazzi AA, et al. Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage[J]. Neurosurgery, 2014, 75(6): 696-706. DOI: 10.1227/neu.0000000000000524.
[37]	Strahle JM, Mahaney KB, Morales DM, et al. Longitudinal CSF iron pathway proteins in posthemorrhagic hydrocephalus: associations with ventricle size and neurodevelopmental outcomes[J]. Ann Neurol, 2021, 90(2): 217-226. DOI: 10.1002/ana.26133.
[38]	Wan Y, Fu X, Zhang T, et al. Choroid plexus immune cell response in murine hydrocephalus induced by intraventricular hemorrhage[J]. Fluids Barriers CNS, 2024, 21(1): 37. DOI: 10.1186/s12987-024-00538-4.
[39]	Tan X, Chen J, Keep RF, et al. Prx2 (peroxiredoxin 2) as a cause of hydrocephalus after intraventricular hemorrhage[J]. Stroke, 2020, 51(5): 1578-1586. DOI: 10.1161/strokeaha.119.028672.
[40]	Bian C, Wan Y, Koduri S, et al. Iron-induced hydrocephalus: The role of choroid plexus stromal macrophages[J]. Transl Stroke Res, 2023, 14(2): 238-249. DOI: 10.1007/s12975-022-01031-6.
[41]	Chen T, Tan X, Xia F, et al. Hydrocephalus induced by intraventricular peroxiredoxin-2: the role of macrophages in the choroid plexus[J]. Biomolecules, 2021, 11(5): 654. DOI: 10.3390/biom11050654.
[42]	Gu C, Hao X, Li J, et al. Effects of minocycline on epiplexus macrophage activation, choroid plexus injury and hydrocephalus development in spontaneous hypertensive rats[J]. J Cereb Blood Flow Metab, 2019, 39(10): 1936-1948. DOI: 10.1177/0271678x19836117.
[43]	Toft-Bertelsen TL, Barbuskaite D, Heerfordt EK, et al. Lysophosphatidic acid as a CSF lipid in posthemorrhagic hydrocephalus that drives CSF accumulation via TRPV4-induced hyperactivation of NKCC1[J]. Fluids Barriers CNS, 2022, 19(1): 69. DOI: 10.1186/s12987-022-00361-9.
[44]	Li Y, Nan D, Liu R, et al. Aquaporin 4 mediates the effect of iron overload on hydrocephalus after intraventricular hemorrhage[J]. Neurocrit Care, 2024, 40(1): 225-236. DOI: 10.1007/s12028-023-01746-w.
[45]	Yung YC, Mutoh T, Lin ME, et al. Lysophosphatidic acid signaling may initiate fetal hydrocephalus[J]. Sci Transl Med, 2011, 3(99): 99ra87. DOI: 10.1126/scitranslmed.3002095.
[46]	Lummis NC, Sánchez-Pavón P, Kennedy G, et al. LPA1/3 overactivation induces neonatal posthemorrhagic hydrocephalus through ependymal loss and ciliary dysfunction[J]. Sci Adv, 2019, 5(10): eaax2011. DOI: 10.1126/sciadv.aax2011.
[47]	Preston D, Simpson S, Halm D, et al. Activation of TRPV4 stimulates transepithelial ion flux in a porcine choroid plexus cell line[J]. Am J Physiol Cell Physiol, 2018, 315(3): C357-C366. DOI: 10.1152/ajpcell.00312.2017.
[48]	Simpson S, Preston D, Schwerk C, et al. Cytokine and inflammatory mediator effects on TRPV4 function in choroid plexus epithelial cells[J]. Am J Physiol Cell Physiol, 2019, 317(5): C881-C893. DOI: 10.1152/ajpcell.00205.2019.
[49]	Ross ME. Unlocking the genetic complexity of congenital hydrocephalus[J]. Nat Med, 2020, 26(11): 1682-1683. DOI: 10.1038/s41591-020-1120-0.
[50]	Luyt K, Jary S, Lea C, et al. Ten-year follow-up of a randomised trial of drainage, irrigation and fibrinolytic therapy (DRIFT) in infants with post-haemorrhagic ventricular dilatation[J]. Health Technol Assess, 2019, 23(4): 1-116. DOI: 10.3310/hta23040.
[51]	Etus V, Kahilogullari G, Karabagli H, et al. Early endoscopic ventricular irrigation for the treatment of neonatal posthemorrhagic hydrocephalus: a feasible treatment option or not? A multicenter study[J]. Turk Neurosurg, 2018, 28(1): 137-141. DOI: 10.5137/1019-5149.Jtn.18677-16.0.
[52]	Parenrengi MA, Ranuh I, Suryaningtyas W. Is ventricular lavage a novel treatment of neonatal posthemorrhagic hydrocephalus? A meta analysis[J]. Childs Nerv Syst, 2023, 39(4): 929-935. DOI: 10.1007/s00381-022-05790-3.
[53]	Dvalishvili A, Khinikadze M, Gegia G, et al. Neuroendoscopic lavage versus traditional surgical methods for the early management of posthemorrhagic hydrocephalus in neonates[J]. Childs Nerv Syst, 2022, 38(10): 1897-1902. DOI: 10.1007/s00381-022-05606-4.

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