Highly aggressive gliomas remain difficult to treat because of their marked invasiveness, frequent recurrence, and association with glioma-related epilepsy. Increasing evidence suggests that ion channels expressed in glioma cells, including voltage-gated Na[+] channels, large-conductance Ca[2+]-activated K[+] (BKCa) channels, intermediate-conductance Ca[2+]-activated K[+] (IKCa) channels, and inwardly rectifying K[+] (Kir) channels, contribute to these malignant phenotypes and represent potential therapeutic targets. This perspective summarizes current evidence for eight representative drugs and phytoconstituents-perampanel, valproic acid, cilostazol, berberine, oxaliplatin, temozolomide, arecoline, and triptolide-that modulate these ion channels. Perampanel and valproic acid suppress voltage-gated Na[+] current in glioma cells and may provide additional benefits in controlling glioma-associated epilepsy. Cilostazol activates BKCa channels, whereas berberine, oxaliplatin, and temozolomide inhibit IKCa channel activity. Arecoline suppresses IKCa and Kir channel activity, while triptolide inhibits Kir channels. These observations suggest that ion channel modulation may influence glioma cell proliferation, migration, invasion, and excitability. To complement the available experimental evidence, we performed molecular docking analyses as a hypothesis-generating approach to explore potential ligand-channel interactions. Because these computational predictions have not been experimentally validated, they should be interpreted cautiously and viewed as a framework for future mechanistic studies rather than definitive evidence of binding. We also discuss important translational considerations, including the limited clinical evidence and the toxicity profiles of several compounds. In particular, arecoline is associated with carcinogenicity and neurotoxicity, triptolide with significant systemic toxicity, berberine with poor oral bioavailability and potential drug interactions, and oxaliplatin with dose-limiting neurotoxicity. Overall, this perspective highlights ion channels as promising therapeutic targets in glioma while emphasizing the need for rigorous experimental validation and careful evaluation of safety before clinical translation.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice, and hypersensitivity reactions to them are not uncommon. Although ibuprofen and indobufen have different clinical indications, both exert their effects through cyclooxygenase inhibition, suggesting a potential risk of cross-reactivity. This report describes a 52-year-old female patient who experienced pruritus, facial and eyelid edema, tearing, and ocular itching approximately half an hour after two separate exposures to ibuprofen in the past. During the current hospitalization for cerebral infarction, she received indobufen for antiplatelet therapy and developed similar symptoms-eyelid edema, tearing, and pruritus of the head and face-within approximately 10 min. The suspected drug was discontinued and antihistamine therapy was administered, following which the symptoms resolved. Subsequent continued use of other concomitant medications, along with antiplatelet therapy with clopidogrel and cilostazol, did not elicit any allergic reactions; this case suggests indobufen as a possible culprit allergen, and its shared COX-1 inhibitory mechanism with ibuprofen-despite their different chemical groups-raises the possibility of cross-reactive hypersensitivity between the two agents, although this inference remains to be confirmed. Although allergic reactions to indobufen are rare in clinical practice, clinicians should remain vigilant about the potential risk of cross-reactivity when prescribing indobufen to patients with a history of NSAID hypersensitivity.

Sorafenib, an established multi-kinase inhibitor, is a cornerstone treatment for advanced hepatocellular carcinoma (HCC). This study evaluated the efficacy of combining sorafenib with cilostazol, a phosphodiesterase-3 inhibitor with emerging anticancer properties, in HepG2 cells. Cell proliferation, apoptosis, and expression of VEGF, SMAD4, Bcl-2, TGF-beta, Bax, and caspase-3 were assessed. Combination treatment significantly reduced the IC50 of sorafenib and markedly decreased colony formation compared with either monotherapy. Enhanced apoptosis was observed through increased Bax and caspase-3 levels and reduced Bcl-2 expression. In addition, combined treatment produced potent anti-angiogenic effects through suppression of VEGF and TGF-beta. These findings demonstrate a synergistic interaction between sorafenib and cilostazol and suggest that this combination may represent a promising therapeutic strategy for hepatocellular carcinoma management.

Background/Objectives: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4-5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated prognostic factors for functional recovery, with particular emphasis on the potential benefit of adjunctive cilostazol, a phosphodiesterase-3 inhibitor with vasodilatory and antiplatelet properties. Methods: This multicenter retrospective cohort study analyzed 394 patients with WFNS grade 4-5 aneurysmal SAH treated at 10 institutions between 2018 and 2024. The primary outcome was favorable functional status (modified Rankin Scale 0-2) at 6 months. Multivariable logistic regression was performed to identify independent predictors of outcome. Sensitivity analyses were also performed to assess the potential influence of missing 6-month outcome data. Results: Six-month outcomes were available for 318 patients (80.7%), of whom 107 (33.6%) achieved favorable recovery. Patients with favorable outcomes were significantly more likely to have received cilostazol than those with unfavorable outcomes (70.1% vs. 55.5%; p = 0.016). In multivariable logistic regression, cilostazol use remained associated with a favorable outcome (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.01-5.22; p = 0.048) after adjustment for age (OR 0.95; p < 0.001), WFNS grade 5 (OR 0.46; p = 0.012), ventricular drainage, and cerebral infarction. Sensitivity analyses, including propensity score-weighted and missing-outcome analyses, yielded directionally favorable estimates but were not statistically significant. Conclusions: Despite the severity of the initial insult, one-third of patients with available 6-month follow-up achieved functional independence. Cilostazol use was associated with favorable functional outcome in the primary analysis, although statistical significance was not retained in sensitivity analyses addressing missing outcomes. These findings suggest a potential therapeutic signal of cilostazol in poor-grade aneurysmal SAH, warranting prospective validation.

Persistent claudication after lumbar spinal surgery may reflect unrecognised peripheral artery disease (PAD) and delayed implementation of secondary cardiovascular prevention. Despite effective guideline-directed therapy, diagnostic and treatment gaps persist in routine practice. Vascular claudication may be under-recognised when exertional lower extremity symptoms are attributed solely to neurogenic causes such as lumbar spinal stenosis. Antiplatelet and statin therapy may be absent even in patients with established PAD, while symptomatic agents such as cilostazol are continued without concurrent secondary prevention. Clinical features supporting vascular rather than neurogenic claudication include reproducible claudication distance, calf-predominant exertional pain, pulse abnormalities, cool extremities and limited posture dependence. Ankle-brachial index (ABI) testing-performed either by Doppler or by validated automated oscillometric devices-provides a practical and guideline-supported first-line diagnostic tool in primary care, with toe-brachial index measurement reserved for patients with non-compressible vessels. This communication provides a primary care reassessment framework integrating symptom-pattern assessment, pulse examination, ABI testing, medication reconciliation and timely vascular referral to reduce diagnostic delay and close secondary prevention gaps in patients with persistent claudication after lumbar spinal surgery. This framework represents a pragmatic clinical approach derived from existing guidelines and observational data; it has not been prospectively validated.

Endovascular treatment has emerged as a cornerstone intervention for acute ischaemic stroke caused by large-vessel occlusion. However, a subset of patients experience futile recanalisation, correlating with unfavourable long-term outcomes. We aimed to investigate the efficacy and safety of Y-6 sublingual tablets (cilostazol and dexborneol) in ischaemic stroke patients with endovascular treatment.

Aneurysmal subarachnoid hemorrhage remains a major cause of neurological morbidity and mortality, with delayed cerebral ischemia and cerebral vasospasm representing important contributors to secondary brain injury and unfavorable functional recovery. Although conventional management strategies such as nimodipine administration, hemodynamic augmentation, and endovascular rescue therapy remain central to clinical practice, growing evidence suggests that delayed cerebral ischemia is a multifactorial neurovascular process extending beyond isolated large vessel vasospasm. This systematic review evaluated emerging neurovascular interventions for the prevention and management of cerebral vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases for studies published between January 2020 and February 2026 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nine studies met the eligibility criteria and were included in the qualitative synthesis. The included interventions encompassed endothelin receptor antagonists, localized nicardipine release implants, intra-arterial nimodipine infusion, microcirculatory targeted pharmacologic therapies, anti-inflammatory neuroprotective agents, and autonomic neuromodulatory approaches. Several interventions demonstrated reductions in angiographic vasospasm, delayed cerebral ischemia incidence, rescue therapy utilization, or cerebral infarction burden. However, consistent improvement in long-term neurological recovery remained variable across studies. Emerging evidence increasingly supports a broader pathophysiological model of delayed cerebral ischemia involving endothelial dysfunction, microcirculatory impairment, neuroinflammation, and autonomic dysregulation in addition to proximal arterial narrowing. Contemporary neurovascular interventions may therefore represent an important shift toward more targeted and mechanistically informed therapeutic strategies after aneurysmal subarachnoid hemorrhage, although further large-scale multicenter investigations remain necessary to establish definitive clinical benefit.

Cerebral amyloid angiopathy (CAA) is a small vessel disease marked by β-amyloid deposition within cortical and leptomeningeal vessels. It is associated with a range of hemorrhagic manifestations, including lobar intracerebral hemorrhage (ICH), cortical superficial siderosis, and convexity subarachnoid hemorrhage (cSAH). In addition to hemorrhagic complications, cerebral ischemic events may occur due to impaired vascular reactivity and reduced cerebral perfusion. The coexistence of ischemic and hemorrhagic strokes in patients with biopsy-confirmed CAA poses significant diagnostic and therapeutic challenges, particularly in relation to antithrombotic use. A 74-year-old woman with type 2 diabetes mellitus and dyslipidemia initially presented with transient focal neurological deficits and subsequently developed left parietal cSAH along with multiple acute infarcts involving the left parietal, temporal, and centrum semiovale regions, for which aspirin and rivaroxaban were initiated. Over the following years, she developed progressive cognitive decline. Three years after her ischemic event, she experienced a lobar ICH in the right frontotemporoparietal region and later suffered another ischemic stroke, prompting treatment with cilostazol. This case illustrates the coexistence of ischemic and hemorrhagic pathology in CAA. Recurrent lobar ICH is a characteristic feature of CAA; however, ischemic events may also occur during its course and can adversely affect prognosis. The lack of clear guidance regarding antithrombotic therapy further complicates management. In this context, cilostazol was selected due to its favorable safety profile in patients at high risk of hemorrhage. This approach underscores the importance of individualized treatment strategies in CAA.