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The SUR1-TRPM4 channel is a critical determinant of edema and hemorrhagic transformation after focal ischemia. Blockade of this channel by the small molecule glyburide results in improved survival and neurological outcome in multiple preclinical models of ischemic stroke. A robust, compelling body of evidence suggests that an intravenous formulation of glyburide, RP-1127, can prevent swelling and improve outcome in patients with stroke. Retrospective studies of diabetic stroke patients show improved outcomes in patients who are continued on sulfonylureas after stroke onset. An early phase II study using magnetic resonance imaging and plasma biomarkers supports the conclusion that RP-1127 may decrease swelling and hemorrhagic transformation. Finally, the ongoing phase II RP-1127 development program has demonstrated continued safety as well as feasibility of enrollment and tolerability of the intervention. Continued efforts to complete the ongoing phase II study and definitive efficacy studies are needed to bring a candidate pharmacotherapy to a population of severe stroke patients that currently have no alternative.
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http://dx.doi.org/10.1007/978-3-319-18497-5_3 | DOI Listing |
Free Radic Biol Med
March 2025
Institute of Structural Pharmacology & TCM Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Wuya College of Innovation, School of Pharmacy, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China. Electronic address:
Ischemic stroke represents a predominant cause of morbidity and mortality globally, resulting from abrupt vascular occlusion or rupture, which precipitates considerable neuronal damage. This study aims to shed more light on the specific neuroprotective mechanisms of Kirenol, a bioactive diterpene derived from traditional herbal medicine, with a particular focus on its regulation of mitochondrial dynamics via the CK2/AKT signalling pathway and its impact on the mitochondrial fusion protein Optic atrophy 1 (Opa1). The effects of Kirenol on neuronal viability, mitochondrial function, and pertinent signalling pathways were evaluated by employing a middle cerebral artery occlusion (MCAO) model in rats and subjecting HT22 neuronal cells to oxidative stress.
View Article and Find Full Text PDFNeurobiol Dis
March 2025
Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, 250 Changgang East Road, Guangzhou 510260, China. Electronic address:
Background: Brainstem stroke accounts only 7-10 % of all ischemic stroke while it had more morbidity and mortality. As the predominant cellular component of nerve tracts, oligodendrocytes might provide some neuroprotection against ischemic injury in the context of brainstem stroke, but the underlying mechanism remains unclear.
Method: A mouse model of brainstem stroke was established, and single-cell RNA sequencing and spatial transcriptomic sequencing analysis were performed to elucidate the phenotype of oligodendrocytes within this context.
J Diabetes Complications
March 2025
Department of Neurology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. Electronic address:
Background: The stress hyperglycemia ratio (SHR), originally proposed in 2015 by Robert et al., is more significantly relevant and predictive of critical illness than absolute hyperglycemia. Several studies have validated the association between stress hyperglycemia ratio and cerebrovascular disease.
View Article and Find Full Text PDFPak J Pharm Sci
March 2025
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Upper limb spasticity is a common and serious sequelae in patients with hemiplegia after stroke. Radial extracorporeal shock wave therapy (rESWT) can improve upper limb dysfunction and relieve pain in patients, However, its efficacy as a single treatment is limited. In traditional Chinese medicine, Tetramethylpyrazine (TMP) is the main pharmacological component of Ligusticum chuanxiong.
View Article and Find Full Text PDFJ Neuroinflammation
March 2025
Jiangxi Key Laboratory of Neurological Diseases, Department of Neurosurgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Clinical studies have revealed a bidirectional relationship between glioma and ischemic stroke, with evidence of spatial overlap between the two conditions. This connection arises from significant similarities in their pathological processes, including the regulation of cellular metabolism, inflammation, coagulation, hypoxia, angiogenesis, and neural repair, all of which involve common biological factors. A significant shared feature of both diseases is the crucial role of extracellular vesicles (EVs) in mediating intercellular communication.
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