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Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca2+ channels (VDCCs) encoded by the gene CaV 2.3. Using in vitro diameter measurements and patch clamp electrophysiology, we have found that L-type VDCC antagonists abolish cerebral artery constriction and block VDCC currents in cerebral artery myocytes from healthy animals. However, 5 days after the intracisternal injection of blood into rabbits to mimic SAH, cerebral artery constriction and VDCC currents were enhanced and partially resistant to L-type VDCC blockers. Further, SNX-482, a blocker of R-type Ca2+ channels, reduced constriction and membrane currents in cerebral arteries from SAH animals, but was without effect on cerebral arteries of healthy animals. Consistent with our biophysical and functional data, cerebral arteries from healthy animals were found to express only L-type VDCCs (CaV 1.2), whereas after SAH, cerebral arteries were found to express both CaV 1.2 and CaV 2.3. We propose that R-type VDCCs may contribute to enhanced cerebral artery constriction after SAH and may represent a novel therapeutic target in the treatment of neurological deficits after SAH.
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http://dx.doi.org/10.1161/01.RES.0000157670.49936.da | DOI Listing |
Background: Hypertension is a risk factor for bleeding events and is included in the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/Alcohol concomitantly)score. However, the effects of blood pressure (BP) and changes in BP on bleeding events in patients undergoing percutaneous coronary intervention (PCI) remain poorly understood. This study is aimed to investigate the relationship between systolic BP (SBP) changes during hospitalisation and bleeding events in patients undergoing PCI.
View Article and Find Full Text PDFActa Med Okayama
December 2024
Department of Cardiovascular Surgery, Kagawa Prefectural Central Hospital.
A 73-year-old man who had undergone esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 8 years prior was transferred to our hospital for the treatment of an acute myocardial infarction. Emergent percutaneous coronary intervention for the left anterior descending artery (#7) was successfully performed. However, echocardiography revealed a ventricular septal rupture (25×27 mm).
View Article and Find Full Text PDFExp Neurol
December 2024
Department of Neurology, Henry Ford Health System, Detroit, MI 48202, United States of America. Electronic address:
Dendritic and axonal plasticity, which mediates neurobiological recovery after a stroke, critically depends on the mitochondrial function of neurons. To investigate, in vivo, neuronal mitochondrial function at the stroke recovery stage, we employed Mito-tag mice combined with cerebral cortical infection of AAV9 produced from plasmids carrying Cre-recombinase controlled by two neuronal promoters, synapsin-I (SYN1) and calmodulin-kinase IIa to induce expression of a hemagglutinin (HA)-tagged enhanced green fluorescence protein (EGFP) that localizes to mitochondrial outer membranes of SYN1 positive (SYN) and CaMKIIa positive (CaMKIIa) neurons. These mice were then subjected to permanent middle cerebral artery occlusion (MCAO) and sacrificed 14 days post stroke.
View Article and Find Full Text PDFJ Stroke Cerebrovasc Dis
December 2024
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213; Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213. Electronic address:
Background: Anterior cerebral artery (ACA) occlusions account for up to 4% of all acute ischemic strokes and may lead to debilitating outcomes. While endovascular thrombectomy (EVT) is a well-established treatment for large vessel occlusions, its efficacy and safety for primary ACA occlusions remains unclear. This systematic review and meta-analysis aims to address this gap by evaluating the clinical outcomes, safety, and efficacy of EVT in the treatment for primary ACA occlusions.
View Article and Find Full Text PDFLife Sci
December 2024
Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Medicine, and Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, United States; Department of Pharmaceutical Sciences, School of Pharmacy, Morgantown, WV, United States; Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States. Electronic address:
Aims: Post stroke hyperglycemia has been shown to deter functional recovery. Earlier findings have indicated the cap-dependent translation regulator 4E-BP1 is detrimentally upregulated in hyperglycemic conditions. The present study aims to test the hypothesis that hyperglycemic ischemic reperfusion injury (I/R) affects normal protein translation poststroke.
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