Drug development in targeting ion channels for brain edema.

Drug development in targeting ion channels for brain edema. Acta Pharmacol Sin. 2020 Aug 27;: Authors: Luo ZW, Ovcjak A, Wong R, Yang BX, Feng ZP, Sun HS Abstract Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial pressure and compromising perfusion. Mortality due to cerebral edema is high. With mortality rates up to 80% in severe cases of stroke, it is the leading cause of death within the first week. Similarly, cerebral edema is devastating for patients of TBI, accounting for up to 50% mortality. Currently, the available treatments for cerebral edema include hypothermia, osmotherapy, and surgery. However, these treatments only address the symptoms and often elicit adverse side effects, potentially in part due to non-specificity. There is an urgent need to identify effective pharmacological treatments for cerebral edema. Currently, ion channels represent the third-largest target class for drug development, but their roles in cerebral edema remain ill-defined. The present review aims to provide an overview of the proposed roles of ion channels and transporters (including aquaporins, SUR1-TRPM4, chloride channels, glucose transporters, and proton-sensitive channels) in mediating cerebral edema...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research

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In this study, 5% of VF arrest was due to PE: V fib is initial rhythm in PE in 3 of 60 cases. On the other hand, if the presenting rhythm is PEA, then pulmonary embolism is likely.  When there is VF in PE, it is not the initial rhythm, but occurs after prolonged PEA renders the myocardium ischemic.--Another study by Courtney and Kline found that, of cases of arrest that had autopsy and found that a presenting rhythm of VF/VT had an odds ratio of 0.02 for massive pulmonary embolism as the etiology, vs 41.9 for PEA.    ===================================MY Comment by KEN ...
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
This study proposes a multi-center RCT in order to compare outcomes of warmer hypothermic strategies during aortic hemiarch surgery on a composite endpoint of neurologic and acute kidney injury (AKI).Methods/designThis is a prospective multi-center, single-blind two-arm RCT comparing mild (32  °C) versus moderate (26 °C) hypothermic cardiac arrest in patients (n = 282) undergoing hemiarch surgery with antegrade cerebral perfusion (ACP). The primary endpoint is a composite of neurological injury (incidence of transient ischemic attack and/or stroke) and Kidney Disease Improving Global Out...
Source: Trials - Category: Research Source Type: clinical trials
Publication date: Available online 4 July 2019Source: Journal of Thermal BiologyAuthor(s): Yannick Lutz, Axel Loewe, Stephan Meckel, Olaf Dössel, Giorgio CattaneoAbstractLocal brain hypothermia is an attractive method for providing cerebral neuroprotection for ischemic stroke patients and at the same time reducing systemic side effects of cooling. In acute ischemic stroke patients with large vessel occlusion, combination with endovascular mechanical recanalization treatment could potentially allow for an alleviation of inflammatory and apoptotic pathways in the critical phase of reperfusion. The direct cooling of arte...
Source: Journal of Thermal Biology - Category: Biology Source Type: research
In this issue of the Journal, Ghoreishi and colleagues1 have performed a tour de force in attempting to analyze 5 major factors potentially associated with stroke after type A aortic dissection repair. The etiology of stroke after aortic surgery is an entanglement of numerous complex factors that place patients at risk for both ischemic and embolic neurologic insults. Decisions about the extent of surgical repair, cannulation site, cerebral perfusion strategy, and degree of hypothermia are all interrelated.
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Commentary Source Type: research
This study compared two different established neuroprotective strategies in patients undergoing elective transverse hemiarch replacement.MethodsTwenty patients undergoing hemiarch replacement were prospectively randomized to receive deep hypothermic circulatory arrest with retrograde cerebral perfusion (DHCA+RCP) or moderate hypothermic circulatory arrest with antegrade cerebral perfusion (MHCA+ACP). All patients received neurologist-adjudicated examinations and magnetic resonance imaging before discharge. The primary end point was a composite of stroke, transient ischemic attack, and magnetic resonance imaging–adjud...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
This study investigates in the temperature distribution of the head within selective brain cooling (SBC). Anatomically accurate geometries based on CT images of head and neck regions are used to develop the 3D geometry and physical model for the finite element modeling. Two cooling methods, the direct head surface cooling strategy and the combination cooling strategy of both head and neck, are evaluated to analyze the inducing hypothermia. The results show that for direct head surface cooling, the scalp and skull temperatures decrease significantly as the blood perfusion rate is constrained, but it is hard to affect the br...
Source: Medical and Biological Engineering and Computing - Category: Biomedical Engineering Source Type: research
Publication date: Available online 15 November 2018Source: The Annals of Thoracic SurgeryAuthor(s): Bradley G. Leshnower, Srikant Rangaraju, Jason W. Allen, Anthony Y. Stringer, Thomas G. Gleason, Edward P. ChenAbstractBackgroundPatients undergoing aortic arch replacement are at high risk for neurologic injury. The purpose of this study was to compare two different established neuroprotective strategies in patients undergoing elective transverse hemiarch replacement.MethodsTwenty patients undergoing hemiarch replacement were prospectively randomized to receive either: Deep Hypothermic Circulatory Arrest + Retrograde Cerebr...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
Abstract BACKGROUND: Patients undergoing aortic arch replacement are at high risk for neurologic injury. The purpose of this study was to compare two different established neuroprotective strategies in patients undergoing elective transverse hemiarch replacement. METHODS: Twenty patients undergoing hemiarch replacement were prospectively randomized to receive either: Deep Hypothermic Circulatory Arrest + Retrograde Cerebral Perfusion(DHCA+RCP) or Moderate Hypothermic Circulatory Arrest + Antegrade Cerebral Perfusion(MHCA+ACP). All patients received Neurologist-adjudicated exams and MRI's prior to discharge. T...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Ann Thorac Surg Source Type: research
Conclusions Hypothermia is protective following ischemic stroke and can reduce brain tissue loss. Moreover, hypothermia shifts the polarization of microglia from the M1 to the M2 phenotype in the ischemic mice brain. This observed biological phenomenon may partially explain the protective effects seen due to hypothermia in acute ischemic stroke. PMID: 29619889 [PubMed - as supplied by publisher]
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
ABSTRACTPURPOSE OF REVIEWNeonatal encephalopathy is the most common condition in neonates encountered by child neurologists. The etiology is most often global hypoxia-ischemia due to failure of cerebral perfusion to the fetus caused by uterine, placental, or umbilical cord compromise prior to or during delivery. Other etiologies of neonatal encephalopathy include ischemic stroke and intracranial hemorrhage, infection, developmental anomalies, and inborn errors of metabolism.RECENT FINDINGSTherapeutic hypothermia is standard of care for the treatment of neonatal encephalopathy presumed to be caused by hypoxia-ischemia. The ...
Source: CONTINUUM: Lifelong Learning in Neurology - Category: Neurology Tags: Review Articles Source Type: research
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