Editorial: Inflammaton in Neurovascular Disorders and Stroke

Mohd Kaisan Mahadi^1*Rony Abdi Syahputra²Mohd Farooq Shaikh³

• ¹Faculty of Pharmacy, National University of Malaysia, Kuala Lumpur, Malaysia
• ²Universitas Sumatera Utara Fakultas Farmasi, Medan, Indonesia
• ³Charles Sturt University School of Dentistry and Health Sciences, Orange, Australia

Ischemia-reperfusion (I/R) injury refers to the paradoxical worsening of cellular dysfunc=on that occurs following the restora=on of blood flow aSer an ischemic stroke. A study by Deng et al. (2025) demonstrates a strong associa=on between the inflammatory marker neutrophil-albumin ra=o and poor clinical outcomes in stroke pa=ents post-thrombolysis, sugges=ng its predic=ve capability in determining I/R injury. A notable manifesta=on of I/R injury is the development of hemorrhagic transforma=on (HT) and symptoma=c intracranial haemorrhage (sICH). Bao et al. (2025) inves=gated the role of peripheral immune inflamma=on in HT and sICH following endovascular thrombectomy in 81 acute ischemic stroke pa=ents. Their study iden=fied interleukin-6 (IL-6) and the neutrophil-toalbumin ra=o as promising biomarkers for predic=ng complica=ons aSer endovascular thrombectomy, thereby aiding in prognosis and clinical management. Similarly, Qian et al. (2025) conducted a retrospec=ve analysis of 323 pa=ents with large artery occlusion who were treated with mechanical thrombectomy. They found that an elevated systemic immune-inflamma=on index on admission was a significant predictor of HT, malignant brain oedema, poor 90-day func=onal outcomes, and mortality. These findings highlight the prognos=c value of the neutrophil-albumin ra=o and the systemic immune inflamma=on index, sugges=ng that targe=ng inflamma=on may improve outcomes following reperfusion therapy.Inflammatory responses determine the pathogenesis and severity of ischemic stroke injury. In experimental models, focal cerebral ischemia triggers a progressive recruitment and ac=va=on of inflammatory cells, including neutrophils, T lymphocytes, and monocytes/macrophages, to facilitate =ssue repair and regenera=on (1-3). Li et al. (2025) employed bioinforma=cs to iden=fy 33 nucleo=de metabolism-related genes associated with immune and inflammatory pathways in ischemic stroke, as retrieved from the GEO database. Among these, CFL1, HMCES, and GIMAP1 emerged as key immunerelated genes with strong diagnos=c poten=al and associa=ons with immune cell infiltra=on. Subsequent drug-target predic=on, single-cell RNA sequencing, molecular docking, and in vivo valida=on reinforced these findings. Exosomes which are small vesicles released by cells to mediate intercellular signalling, have been shown to influence the inflammatory response aSer stroke. Zhao et al. (2025) integrated mul=omics data from five ischemic stroke datasets with exosome-related genes, applying machine learning and network analyses to iden=fy 13 features and 10 hub genes. Notably, LGALS3, CD36, TLR2, ICAM1, and CD14 were upregulated in mouse stroke models, implica=ng inflammatory, chemokine, and JAK-STAT signalling pathways. Immune infiltra=on analysis revealed altered immune cell popula=ons, with CD14 and LGALS3 linked to monocytes/macrophages and neutrophil ac=vity. Single-cell analysis highlighted microglial dynamics, posi=oning exosomal genes as promising therapeu=c targets in ischemic stroke. Targe=ng inflamma=on offers therapeu=c promise in stroke management. Nevertheless, suppressing the inflammatory responses has been suggested to reduce the size of the infarct and enhance neurological recovery in ischemic stroke injury (4). Corbali (2025) indicated that colchicine, an NLRP3 inflammasome inhibitor, could reduce stroke risk in cardiovascular pa=ents under the age of 65. However, stroke-specific trials (CONVINCE, CHANCE-3) yielded limited or no significant benefit. Lowdose colchicine (0.5 mg daily) is generally safe but may cause myopathy, par=cularly with sta=ns. Current guidelines cau=ously endorse colchicine for atherosclero=c stroke preven=on, pending further valida=on. Nevertheless, it is also essen=al to consider that the latest Cochrane stroke group reported that randomised trials on an=-inflammatory therapy did not produce any benefits against recurrent stroke (5). A preclinical study by Cao et al (2025) highlights cynaroside (Cyn) as a poten=al neuroprotec=ve agent. Cyn treatment improved neurological outcomes, reduced infarct size, oedema, and microglial ac=va=on in ischemia/reperfusion models by inhibi=ng arachidonate 15-lipoxygenase (Alox15), a key enzyme in inflamma=on and ferroptosis. This inhibi=on decreased pro-inflammatory cytokines (NLRP3, IL-1β, and IL-18) and ferroptosis-related proteins (Tfrc, COX2, and Acsl4), sugges=ng that Cyn mi=gates ischemic injury via an=-inflammatory and an=-ferropto=c mechanisms. Further research is warranted to confirm these therapeu=c effects and clinical applicability.Integra=ng mul=ple modali=es is necessary in managing stroke associated injuries. Cao et al 2025 develop and validate a machine learning-based model to predict stroke-associated pneumonia (SAP) in older adults with hemorrhagic stroke. Analysis performed on clinical data from 788 pa=ents across mul=ple centers, comparing four algorithms: XGBoost, Logis=c Regression, Support Vector Machine (SVM), and Naive Bayes. Key risk factors iden=fied included advanced age, smoking history, lower Glasgow Coma Scale and Braden scores, and use of nasogastric tubes. The model was visualized via a nomogram to enable rapid bedside risk assessment, facilita=ng early iden=fica=on and targeted preven=on to reduce SAP incidence and improve outcomes. In another study, Liao et al (2025) evaluated CTA angiographic point sign-guided stereotac=c surgery in 143 pa=ents with moderate basal ganglia hematoma. Compared to CT-guided surgery, the CTA-guided approach significantly reduced secondary hematoma expansion (0% vs. 18.75%), lowered mortality (2.53% vs. 12.5%), decreased lung infec=ons, and improved 6-month func=onal outcomes, demonstra=ng enhanced safety and efficacy. He et al 2025 examined 158 stroke neurosyphilis pa=ents treated with combined hyperbaric oxygen (HBO) and transcranial ultrasound neuromuscular s=mula=on (TUS-NMES) showed significant improvements in motor, cogni=ve, and daily living func=ons. Decreased inflammatory marker CXCL13 levels correlated with recovery, and a biomarker panel of CXCL13, WBC, and Hs-CRP effec=vely predicted rehabilita=on outcomes, suppor=ng their clinical use in managing neurosyphilis stroke recovery.In conclusion, understanding and targe=ng inflammatory pathways via mul=ple modali=es offers a promising therapeu=c avenue for mi=ga=ng brain injury associated with stroke. Emerging evidence from therapies like colchicine and cynaroside highlights their poten=al to modulate inflamma=on; however, further rigorous inves=ga=on is crucial to establish their defini=ve benefits and safety for pa=ent applica=on. Moving forward, the synergis=c integra=on of insights from basic laboratory research and clinical studies will be essen=al for developing personalised treatments that significantly enhance outcomes for individuals affected by stroke.