Abstract:
:Activation and repression of gene expression are key features of ischemic tolerance. Converging lines of inquiry from several groups suggests that epigenetic proteins may transduce sublethal stresses, including bioenergetic or oxidative stress into durable (2-3 days) changes in gene expression that mediate ischemic tolerance. Here we discuss the potential mechanisms by which changes in cell state (e.g., ATP, NAD+, and oxygen) can modify specific targets including polycomb complexes, jumonji domain histone demethylases, and zinc and NAD-dependent histone decetylases and thus trigger an adaptive program. A major unanswered question is whether these proteins work in parallel or convergently as part of a "tolerosome" (tolero is the Latin word for tolerance), a multiprotein complex recruited to promoters or enhancers of specific genes, to mediate preconditioning. Whatever the case may be, epigenetic proteins are fertile targets for the treatment of stroke.
journal_name
Transl Stroke Resjournal_title
Translational stroke researchauthors
Brand D,Ratan RRdoi
10.1007/s12975-012-0235-0subject
Has Abstractpub_date
2013-02-01 00:00:00pages
56-62issue
1eissn
1868-4483issn
1868-601Xjournal_volume
4pub_type
杂志文章,评审abstract::Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-017-0565-z
更新日期:2018-04-01 00:00:00
abstract::Polymorphonuclear neutrophils (PMNs) infiltration into brain parenchyma after cerebrovascular accidents is viewed as a key component of secondary brain injury. Interestingly, a recent study of ischemic stroke suggests that after ischemic stroke, PMNs do not enter brain parenchyma and as such may cause no harm to the b...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-014-0341-2
更新日期:2014-10-01 00:00:00
abstract::The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective effects, mediated via suppression of iron-induced hydroxyl radical formation, in various animal models of ischemic and hemorrhagic stroke. Therefore, the objective of this study was to investigate whether DFO can exert similar actions in stroke ...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-009-0001-0
更新日期:2010-03-01 00:00:00
abstract::Motor impairment is the most common complication after stroke, and recovery of motor function has been shown to be dependent on the extent of lesion in the ipsilesional corticospinal tract (iCST) and activity within ipsilesional primary and secondary motor cortices. However, work from neuroimaging research has suggest...
journal_title:Translational stroke research
pub_type: 杂志文章,评审
doi:10.1007/s12975-017-0551-5
更新日期:2017-12-01 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::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::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::Infection is a leading cause of death in patients with stroke; however, the impact of cerebral infarct size or location on infectious outcome is unclear. To examine the effect of infarct size on post-stroke infection, we utilised the intraluminal middle-cerebral artery occlusion (MCAO) mouse model of ischemic stroke a...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-019-00738-3
更新日期:2020-06-01 00:00:00
abstract::Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related gene...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-017-0577-8
更新日期:2018-06-01 00:00:00
abstract::Cerebral hyperperfusion syndrome (CHS) is a complication that can occur after carotid endarterectomy (CEA), the treatment of choice to decrease the subsequent risk of fatal or disabling stroke for patients with symptomatic severe stenosis of the carotid artery. Because of its rarity and complexity, the mechanism of th...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-017-0605-8
更新日期:2018-10-01 00:00:00
abstract::Acute ischemic stroke (AIS) often results in degeneration of the blood-brain barrier (BBB), which can lead to vasogenic edema and an increased risk of intracerebral hemorrhage. Imatinib is an agent that may be able to protect the BBB and reduce the risk of the harmful consequences of BBB degeneration. We sought to mea...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-014-0358-6
更新日期:2015-02-01 00:00:00
abstract::Intracerebral hemorrhage is by far the most destructive form of stroke. Apart from the management in a specialized stroke or neurological intensive care unit (NICU), no specific therapies have been shown to consistently improve outcomes after ICH. Current guidelines endorse early aggressive optimization of physiologic...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-012-0175-8
更新日期:2012-07-01 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::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::Ischemic stroke is a devastating neural event as currently no therapies other than physical rehabilitation are available to enhance recovery after stroke. To identify endogenous mediators to repair stroke brain, we performed the expression profiling analysis of transcripts in the mouse photothrombotic stroke brain. Ba...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-015-0401-2
更新日期:2015-08-01 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::Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular disease...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-017-0585-8
更新日期:2018-06-01 00:00:00
abstract::Anticoagulation increases the risk of intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA), so the management of stroke-risk in patients with both atrial fibrillation (AF) and CAA is controversial. Advances in left atrial appendage closure (LAAC) techniques provide a stroke-risk-reduction ...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-020-00838-5
更新日期:2020-08-07 00:00:00
abstract::Monocytes recruitment from the blood to inflamed tissues following ischemic stroke is an important immune response to wound healing and tissue repair. Mouse monocytes can be endogenously divided into two distinct populations: pro-inflammatory or classical monocytes that express CCR2highCX3CR1low and circulate in blood...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-020-00878-x
更新日期:2021-01-06 00:00:00
abstract::The most deadly form of stroke, intracerebral hemorrhage (ICH) continues to puzzle researchers and produce substantial decrements in the quality of patients' lives. Intensive basic research has devised many agents with putative benefit in mitigating the devastating effects of ICH, but these therapies have been largely...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-012-0207-4
更新日期:2012-12-01 00:00:00
abstract::Subarachnoid haemorrhage (SAH) is a devastating disease and a major burden on society. Despite this, pharmacological treatment options are limited. Appropriate animal modelling of SAH is essential for the development of neuroprotective drugs, but experimental SAH often fails to produce widespread neuronal loss, as fre...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-011-0124-y
更新日期:2012-03-01 00:00:00
abstract::Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment...
journal_title:Translational stroke research
pub_type: 杂志文章,评审
doi:10.1007/s12975-013-0287-9
更新日期:2014-04-01 00:00:00
abstract::Cavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1, CCM2, and CCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to e...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-019-00725-8
更新日期:2020-06-01 00:00:00
abstract::Hydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition's high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health syste...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-019-00697-9
更新日期:2019-12-01 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::Aneurysmal subarachnoid hemorrhage comprises of an early phase after the bleeding and a late phase of delayed consequences of the bleeding. The development of delayed injury mechanisms, like the reduction of cerebral blood flow (CBF) due to cerebral vasospasm (CVS), seems mainly to depend on the amount and the duratio...
journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-015-0392-z
更新日期:2015-06-01 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::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::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