Section of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy.
Published: June 2013
AI Article Synopsis
Article Abstract
Thrombolytic therapy is the cornerstone of treatment of acute atherothrombotic ischemic stroke but is associated with brain hemorrhage; antiplatelet therapy has limited efficacy and is still associated with intracranial bleeding. Therefore, new antithrombotic approaches with a better efficacy/safety ratio are required. We have assessed the effect of ALX-0081, a Nanobody against the A1 domain of von Willebrand factor (VWF) that blocks VWF binding to GPIb, of the thrombolytic agent recombinant tissue plasminogen activator (rtPA), and of the GPIIb/IIIa antagonist tirofiban, in a middle cerebral artery (MCA) thrombosis model in guinea pigs. Drugs were administered before, immediately after, or 15 or 60 minutes after the total occlusion of the MCA. ALX-0081 prevented MCA thrombosis and induced reperfusion when given immediately after and 15 minutes after complete occlusion and reduced brain damage without inducing hemorrhage, whereas tirofiban prevented thrombosis but did not induce reperfusion and induced striking brain hemorrhage. rtPA also induced reperfusion when given 60 minutes after occlusion but provoked brain hemorrhage. Skin bleeding time was not modified or was moderately prolonged by ALX-0081, whereas tirofiban and rtPA prolonged it. The inhibition of the GPIb-VWF axis in guinea pigs prevents cerebral artery thrombosis and induces early reperfusion without provoking intracerebral bleeding thus reducing brain infarct area.
Chronic cerebral hypoperfusion (CCH) is a crucial mechanism causing vascular cognitive impairment (VCI). Choline is metabolized by gut microbiota into trimethylamine N-oxide (TMAO), a risk factor of cardiovascular diseases and cognitive impairment. However, the impact of choline-TMAO pathway on CCH-induced VCI is elusive.
The brain is highly innervated by sympathetic nerve fibres; however, their physiological purpose is poorly understood. We hypothesized that unilateral cerebral norepinephrine (NE) spillover, an index of cerebral sympathetic nerve activity (SNA), would be elevated when engaging the baroreflex [via lower-body negative pressure (LBNP; -20 and -40 Torr)] and respiratory chemoreflexes [via carbon dioxide (CO) administration (+8 Torr)], independently, and in combination. Twelve young and healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and internal jugular vein.
Background: Cerebral ischemia or stroke is the second leading cause of death in the world, and most surviving patients suffer from long-term physical and cognitive disabilities, which create many social and economic problems for them and society. Visual attention impairment is a common cognitive complication among patients with cerebral ischemia, especially in the Middle Cerebral Artery (MCA). One way to improve attention in these patients is cognitive rehabilitation.
Background: Stroke, primarily known as ischemic stroke, is a leading cause of mortality and disability worldwide. Reperfusion after the ischemia stroke resolves is necessary for maintaining the health of brain tissues; however, it also induces inflammation and oxidative stress, resulting in brain injury. This study aimed to investigate the role of circ0001679 in the pathology of I/R (Ischemia/Reperfusion)-induced brain injury and explore its therapeutic potential for I/R injury.
