Abstract：
:Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus. Furthermore, 12/15-LOX co-localized with apoptosis-inducing factor (AIF), a mediator of non-caspase-related apoptosis in the cortex. In contrast, caspase-3 activation was more prevalent in the hippocampus. 12/15-lipoxygenase knockout mice were protected against global cerebral ischemia compared to wild-type mice, accompanied by reduced neurologic impairment. The lipoxygenase inhibitor LOXBlock-1 similarly reduced neuronal cell death both when pre-administered and when given at a therapeutically relevant time point 1 h after onset of ischemia. These findings suggest a pivotal role for 12/15-LOX in both caspase-dependent and caspase-independent apoptotic pathways following global cerebral ischemia and suggest a novel therapeutic approach to reduce brain injury following cardiac arrest.
journal_name
Transl Stroke Resjournal_title
Translational stroke researchauthors
Yigitkanli K,Zheng Y,Pekcec A,Lo EH,van Leyen Kdoi
10.1007/s12975-016-0509-zsubject
Has Abstractpub_date
2017-04-01 00:00:00pages
194-202issue
2eissn
1868-4483issn
1868-601Xpii
10.1007/s12975-016-0509-zjournal_volume
8pub_type
杂志文章abstract：:In a porcine ischemic stroke model, we sought to compare the acute predicted infarct core volume (PIV) defined by CT perfusion (CTP)-hemodynamic parameters and MR-diffusion-weighted imaging (MR-DWI)/apparent diffusion coefficient (ADC), with the true infarct core volume (TIV) as defined by histology. Ten Duroc-cross p...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-015-0394-x
更新日期：2015-06-01 00:00:00
abstract：:Pathophysiological findings of early brain injury in humans have not permitted conclusive determinations. We explored the essence of this phenomenon by taking intraoperative cortical specimens of Hunt-Kosnik grades IV~V (poor-grade) subarachnoid hemorrhages (SAH). From 2013 to 2017, we treated 39 consecutive poor-grad...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-020-00875-0
更新日期：2020-11-27 00:00:00
abstract：:Pulmonary complications associated with persistent respiratory muscle weakness, paralysis, and spasticity are among the most important problems faced by patients with spinal cord injury when lack of muscle strength and disorganization of reciprocal respiratory muscle control lead to breathing insufficiency. This revie...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-011-0114-0
更新日期：2011-12-01 00:00:00
abstract：:Poor clinical outcomes despite endovascular therapy (EVT) are common in patients with acute basilar artery occlusion (BAO). We aimed to develop a new angiographic collateral grading system for predicting 90-day functional outcomes of acute BAO after EVT. A prospectively registered consecutive cohort of acute BAO patie...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-020-00856-3
更新日期：2020-09-28 00:00:00
abstract：:In the original publication of the article, there was a switched order of author names. ...
journal_title：Translational stroke research
pub_type： 杂志文章,已发布勘误
doi：10.1007/s12975-018-0618-y
更新日期：2018-12-01 00:00:00
abstract：:Preconditioning is a paradigm in which sublethal stress-prior to a more injurious insult-induces protection against injury. In the central nervous system (CNS), preconditioning against ischemic stroke is induced by short durations of ischemia, brief seizures, exposure to anesthetics, and other stresses. Increasing evi...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-017-0547-1
更新日期：2017-12-01 00:00:00
abstract：:Quantitative susceptibility mapping (QSM) has been recently introduced as a novel MRI post-processing technique of gradient recalled echo (GRE) data. QSM is useful in depicting both brain anatomy and for detecting abnormalities. Its utility in the context of ischemic stroke has, however, not been extensively character...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-017-0591-x
更新日期：2018-08-01 00:00:00
abstract：:Diabetes significantly increases the risk of stroke and post-stroke mortality. Recurrent hypoglycemia (RH) is common among diabetes patients owing to glucose-lowering therapies. Earlier, we showed that RH in a rat model of insulin-dependent diabetes exacerbates cerebral ischemic damage. Impaired mitochondrial function...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-018-0622-2
更新日期：2019-02-01 00:00:00
abstract：:Increasingly, experimental research in subarachnoid hemorrhage (SAH) has investigated early brain injury and the microcirculation. A number of pathophysiological changes occur in the cerebral microvessels after SAH including altered vasoreactivity, vasoconstriction, inflammation, blood-brain barrier impairment, increa...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-014-0323-4
更新日期：2014-04-01 00:00:00
abstract：:For years, strategies have been proposed to improve translational success in stroke research by improving the quality of animal studies. However, articles that report preclinical intracerebral hemorrhage (ICH) studies continue to lack adequate qualitative and quantitative descriptions of fresh brain tissue collection....
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-015-0399-5
更新日期：2015-10-01 00:00:00
abstract：:The long-term effects of multiple sport-related concussions are currently at the center of debate in the popular press and scientific community. The question, "How many concussions are too many," is frequently asked in the competitive sport environment by parents, athletes, and coaches. While research suggests that a ...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-012-0237-y
更新日期：2013-08-01 00:00:00
abstract：:Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-018-0647-6
更新日期：2018-07-12 00:00:00
abstract：:Systemic docosahexaenoic acid (DHA) has been explored as a clinically feasible protectant in stroke models. However, the mechanism for DHA-afforded neuroprotection remains elusive. Transient middle cerebral artery occlusion (tMCAO) was induced for 1 h. DHA (i.p., 10 mg/kg) was administered immediately after reperfusio...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-018-0662-7
更新日期：2018-12-01 00:00:00
abstract：:Intraventricular hemorrhage (IVH), which afflicts thousands of people of all ages every year, frequently results in the development of communicating hydrocephalus. Classically, IVH-induced hydrocephalus has been attributed to reduced resorption of cerebrospinal fluid (CSF) due to dysfunction of arachnoid granulations,...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-011-0070-8
更新日期：2011-06-01 00:00:00
abstract：:Stroke prevention efforts typically focus on either ischemic or hemorrhagic stroke. This approach is overly simplistic due to the frequent coexistence of ischemic and hemorrhagic cerebrovascular disease. This coexistence, termed "mixed cerebrovascular disease", offers a conceptual framework that appears useful for str...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-012-0185-6
更新日期：2012-07-01 00:00:00
abstract：:Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement ex...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-019-00757-0
更新日期：2020-08-01 00:00:00
abstract：:Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for ...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-020-00796-y
更新日期：2020-10-01 00:00:00
abstract：:In clinical trials, assessing efficacy is based on validated scales, and the primary endpoint is usually based on a single scale. The aim of the review is to revisit the concepts and methods to design and analyze studies focused on restoration, recovery and or compensation. These studies are becoming more frequent wit...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-016-0488-0
更新日期：2016-10-01 00:00:00
abstract：:The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 ...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-015-0424-8
更新日期：2015-12-01 00:00:00
abstract：:Lifestyle risk factors, inflammation and genetics play a role in the development of atherosclerosis. We therefore studied Fc gamma receptor (FcγR) polymorphisms, interleukin (IL)-10 polymorphisms and other biomarkers related to carotid intima-media thickness (cIMT) in patients with ischemic stroke at a young age. Pati...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-015-0403-0
更新日期：2015-08-01 00:00:00
abstract：:Magnetic resonance imaging (MRI) has dramatically changed our ability to diagnose and treat stroke as well as follow its evolution and response to treatment. Early stroke and ischemia can be visualized using diffusion-weighted imaging that utilizes water diffusion within tissues as a reporter for evolving neuropatholo...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-011-0139-4
更新日期：2012-03-01 00:00:00
abstract：:This study aimed to investigate whether serum lactate dehydrogenase (LDH) levels predicted hematoma expansion and poor outcomes in intracerebral hemorrhage (ICH) patients. The differentially expressed proteins between patients with and without hematoma expansion were screened using proteomic analysis. Then the critica...
journal_title：Translational stroke research
pub_type： 杂志文章,多中心研究
doi：10.1007/s12975-019-0686-7
更新日期：2019-12-01 00:00:00
abstract：:This review focuses on assessment of behavioral outcomes following traumatic brain injury in juvenile animal models. In the 15 years since the first publication in this field, the majority of studies have used rats roughly equivalent to human toddlers in terms of brain development. Few studies have tested ages closer ...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-011-0132-y
更新日期：2011-12-01 00:00:00
abstract：:Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers....
journal_title：Translational stroke research
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s12975-018-0620-4
更新日期：2018-12-01 00:00:00
abstract：:Although used extensively in stroke research, there is limited knowledge of how 2, 3, 5-triphenyltetrazolium chloride (TTC)-treated rat brain sections are altered and if they can be used for immunohistochemical quantification after staining with TTC. In the present study, we hypothesized that TTC treatment (TTC+) woul...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-017-0604-9
更新日期：2018-10-01 00:00:00
abstract：:Acute ischemic stroke affects over 800,000 US adults annually, with hundreds of thousands more experiencing a transient ischemic attack. Emergent evaluation, prompt acute treatment, and identification of stroke or TIA (transient ischemic attack) etiology for specific secondary prevention are critical for decreasing fu...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-017-0537-3
更新日期：2017-05-05 00:00:00
abstract：:RTL1000 is a partial human MHC molecule coupled to a human myelin peptide. We previously demonstrated that RTL1000 was protective against experimental ischemic stroke in HLA-DR2 transgenic (DR2-Tg) mice. Since thrombolysis with recombinant tissue plasminogen activator (t-PA) is a standard therapy for stroke, we determ...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-014-0348-8
更新日期：2014-10-01 00:00:00
abstract：:Ischemic stroke contributes to the majority of brain injuries and remains to be a leading cause of death and long-term disability. Despite the devastating pathology and high incidence of disease, there remain only few treatment options (TPA and endovascular procedures), which may be hampered by time-dependent administ...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-013-0319-5
更新日期：2014-02-01 00:00:00
abstract：:Rodent animal models of stroke are widely used with brain ischemia inducible by various occlusion methods. Permanent or transient occlusion of the distal portion of the middle cerebral artery (MCAO) offers a reproducible model with low mortality rates, and it is the most likely model of choice for mid- and long-term s...
journal_title：Translational stroke research
pub_type： 杂志文章,评审
doi：10.1007/s12975-012-0234-1
更新日期：2013-06-01 00:00:00
abstract：:Cerebral blood flow (CBF) is the key factor for identifying progressive hypoperfusion that is indicative of numerous pathological conditions. CBF measurement is beneficial for the management of cerebrovascular disease, head injury, and intracranial neoplasms. Of the various imaging modalities developed to assess CBF, ...
journal_title：Translational stroke research
pub_type： 杂志文章
doi：10.1007/s12975-010-0064-y
更新日期：2011-06-01 00:00:00
