# Oxygen Therapy for Intracranial Hemorrhage

**Authors:** Qiqi Shi, Song Han, Xiangyu Li, Jingwei Guan, Yanli Duan, Zhangyuan Liao, Zhiying Chen, Weili Li, Ran Meng, Ming Zou, Jiayue Ding

PMC · DOI: 10.1002/cns.70806 · CNS Neuroscience & Therapeutics · 2026-02-24

## TL;DR

Oxygen therapy may help treat brain hemorrhages by protecting brain cells and improving recovery, but more research is needed to ensure safety and effectiveness.

## Contribution

This review systematically summarizes the neuroprotective mechanisms, effectiveness, and safety of oxygen therapy in intracranial hemorrhage.

## Key findings

- Hyperbaric and normobaric oxygen therapies protect brain cells through anti-inflammatory and metabolic mechanisms.
- Oxygen therapy may improve neurological recovery and reduce mortality in ICH patients.
- Excessive oxygen use poses risks, requiring optimized treatment plans for safe clinical application.

## Abstract

Intracranial hemorrhage (ICH) is a severe cerebrovascular disease with a high mortality rate that impairs patient well‐being and quality of life. Oxygen therapies, including hyperbaric hyperoxia (HBO) and normobaric hyperoxia (NBO), have attracted widespread attention as potential adjuvant treatments because of their neuroprotective effects. This review aimed to summarize the current literature addressing the neuroprotective mechanisms of oxygen therapy in ICH, as well as its effectiveness and safety in patients with ICH.

We systematically searched multiple literature databases including PubMed, Embase, and Cochrane for publications containing specified keywords and published prior to November 2025. The references were thoroughly reviewed to identify other articles that may have been missed in our search.

A total of 38 articles were included in this study. Among them, 20 mainly studied the mechanism of oxygen therapy after ICH, eight mainly investigated the effects of oxygen therapy in patients with ICH, and 10 primarily analyzed the safety of oxygen therapy in patients with ICH. The experimental results showed that the treatment mechanism of HBO mainly involves reducing cerebral vasospasm, promoting angiogenesis, inhibiting inflammatory responses, and improving aerobic energy metabolism, whereas NBO mainly protects the blood–brain barrier (BBB), reduces cerebral edema and hemispheric swelling, mitigates acute inflammation, inhibits oxidative stress and neuronal cell death, and enhances aerobic metabolism. Clinical trials have shown that oxygen therapy can improve neurological function recovery and long‐term prognosis in patients with ICH, as reflected by better scores in some indicators and lower mortality rates; however, oxygen therapy also has controversial and potential risks. Excessive oxygen supply may lead to adverse reactions, and hyperoxia may negatively impact patients with ICH. An appropriate treatment plan should be formulated for the clinical application of oxygen therapy.

Oxygen therapy shows potential in ICH treatment through multiple mechanisms; however, its safety and optimal regimen require further large‐scale randomized controlled trials to balance the benefits and risks and optimize its application strategies.

Oxygen therapies confer neuroprotective effects on patients with intracranial hemorrhage through mechanisms such as anti‐inflammation, reduction of cerebral edema and neuronal death, and enhancement of aerobic metabolism. Clinical evidence suggests that oxygen therapy may improve neurological recovery and decrease mortality in patients with intracranial hemorrhage; however, excessive oxygen administration poses potential risks.

## Full-text entities

- **Genes:** MARCHF8 (membrane associated ring-CH-type finger 8) [NCBI Gene 220972] {aka CMIR, MARCH-VIII, MARCH8, MIR, RNF178, c-MIR}, AQP4 (aquaporin 4) [NCBI Gene 361] {aka MIWC, MLC4, WCH4, hAQP4}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Mir204 (microRNA 204) [NCBI Gene 100314051] {aka rno-mir-204}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, Vwf (von Willebrand factor) [NCBI Gene 116669], PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, PCNA (proliferating cell nuclear antigen) [NCBI Gene 5111] {aka ATLD2}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Clcn3 (Cl-/H+ antiporter 3) [NCBI Gene 84360] {aka ClC-3}, CLCN3 (Cl-/H+ antiporter 3) [NCBI Gene 1182] {aka CLC3, ClC-3, NEDHYBA, NEDSBA}, Ribosomal Protein S6 [NCBI Gene 100338367], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, DUOX2 (dual oxidase 2) [NCBI Gene 50506] {aka LNOX2, NOXEF2, P138-TOX, TDH6, THOX2}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Aif1 (allograft inflammatory factor 1) [NCBI Gene 29427] {aka BART-1, Bart1, iba1, mrf-1}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, HIF-1alpha [NCBI Gene 100009579], Pcna (proliferating cell nuclear antigen) [NCBI Gene 25737] {aka PCNAR, Pcna/cyclin}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, Stat1 (signal transducer and activator of transcription 1) [NCBI Gene 25124] {aka DD6G4-4}, AQP4 [NCBI Gene 100008646], ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}
- **Diseases:** AIS (MESH:D013734), cerebrovascular disease (MESH:D002561), ischemic stroke (MESH:D002544), cerebral ischemic injury (MESH:D017202), brain inflammation (MESH:D004660), SAH (MESH:D013345), cerebral hemorrhage (MESH:D002543), death (MESH:D003643), hyperglycemic (MESH:D006944), hypertensive (MESH:D006973), brain injury (MESH:D001930), to brain tissue (MESH:D001927), memory impairments (MESH:D008569), brain tissue damage (MESH:D017695), coma (MESH:D003128), gastrointestinal bleeding (MESH:D006471), neurological impairment (MESH:D009422), acute subdural hematoma (MESH:D020199), depression (MESH:D003866), infarction (MESH:D007238), neuronal death (MESH:D009410), neuroinflammation (MESH:D000090862), atrophy (MESH:D001284), anxiety (MESH:D001007), hemorrhagic stroke (MESH:D000083302), perihematoma edema (MESH:D004487), BBB damage (MESH:C536830), ischemic brain (MESH:D020520), hemispheric swelling (MESH:D006832), DCI (MESH:D002545), neurotoxicity (MESH:D020258), mitochondrial damage (MESH:D028361), hypertensive intracerebral hemorrhage (MESH:D020299), HBO (MESH:D018496), hematoma (MESH:D006406), hyperglycemia (MESH:D006943), acute inflammation (MESH:D007249), hypoxemia (MESH:D000860), cerebral vasospasm (MESH:D020301), acute ischemic stroke (MESH:D000083242), neurological deficits (MESH:D009461), acute stroke (MESH:D020521), paralysis (MESH:D010243), damage to neurological function (MESH:D003291), Hemorrhagic injury (MESH:D006470), hypoxic (MESH:D002534), ICH (MESH:D020300), brain edema (MESH:D001929)
- **Chemicals:** N-acetyl-aspartate (MESH:C000179), K+ (MESH:D011188), superoxide (MESH:D013481), HBO (-), ROS (MESH:D017382), NAD+ (MESH:D009243), lipid (MESH:D008055), ATP (MESH:D000255), lactate (MESH:D019344), Oxygen (MESH:D010100), phosphates (MESH:D010710), glutamate (MESH:D018698), edaravone (MESH:D000077553), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090]

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## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932117/full.md

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Source: https://tomesphere.com/paper/PMC12932117