The Continued Promise of Neuroprotection for Acute Stroke Treatment.
Authors: Liu S, Levine SR Abstract Stroke is the second leading cause of death. However, effective pharmocologic treatment options are still extremely limited and applicable to only a small fraction of patents. The translational failure in finding an effective neuroprotectant for ischemic strokes has generated an active discussion in this field. One focus has been on validating systems for testing neuroprotectants. This review discusses some fundamental issues in experimental stroke that are worthy of further exploration. We begin with a general review of the current status of experimental stroke research and then ...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Rodent stroke model guidelines for preclinical stroke trials (1st edition).
RODENT STROKE MODEL GUIDELINES FOR PRECLINICAL STROKE TRIALS (1ST EDITION). J Exp Stroke Transl Med. 2009 Jan 1;2(2):2-27 Authors: Liu S, Zhen G, Meloni BP, Campbell K, Winn HR Abstract Translational stroke research is a challenging task that needs long term team work of the stroke research community. Highly reproducible stroke models with excellent outcome consistence are essential for obtaining useful data from preclinical stroke trials as well as for improving inter-lab comparability. However, our review of literature shows that the infarct variation coefficient of commonly performed stroke models r...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Dealing with publication bias in translational stroke research.
Authors: Liu S Abstract Publication bias has been around for about 50 years. It has become a concern for almost 20 years in the medical research community. This review briefly summarizes the current status of publication bias, potential sources where bias may arise from, and its common evaluation methods. In the field of translational stroke research, publication bias has long been suspected; however, it has not been addressed with sufficient efforts. Its status has remained the same during the last decade. The author emphasizes the important role that publishers might play in addressing publication bias. PMID:...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Long-term survival and serial assessment of stroke damage and recovery - practical and methodological considerations.
Authors: Modo M Abstract Impairments caused by stroke remain the main cause for adult disability. Despite a vigorous research effort, only 1 thrombolytic treatment has been approved in acute stroke (
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Fundamentals of clinical trial design.
Authors: Evans SR Abstract Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. Issues in trial conduct and analyses should be anticipated during trial design and thoughtfully addressed. Fundamental clinical trial design issues are discussed. PMID: 21533012 [PubMed - as supplied by publisher] (Source: Journal of Experimental Stroke and Translational Medicine)
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Targeting ischemic penumbra: part I - from pathophysiology to therapeutic strategy.
Authors: Liu S, Levine SR, Winn HR Abstract Penumbra is the viable tissue around the irreversibly damaged ischemic core. The purpose of acute stroke treatment is to salvage penumbral tissue and to improve brain function. However, the majority of acute stroke patients who have treatable penumbra are left untreated. Therefore, developing an effective non-recanalizational therapeutics, such as neuroprotective agents, has significant clinical applications. Part I of this serial review on "targeting penumbra" puts special emphases on penumbral pathophysiology and the development of therapeutic strategies. Bioe...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

A Reproducible and Simple Model of Permanent Cerebral Ischemia in CB-17 and SCID Mice.
Authors: Taguchi A, Kasahara Y, Nakagomi T, Stern DM, Fukunaga M, Ishikawa M, Matsuyama T Abstract In order to evaluate novel stroke therapies, it is essential to utilize a highly reproducible model of focal cerebral ischemia. Though a range of rodent stroke models has been employed in the literature, there are persistent issues regarding reproducibility of the ischemic zone, as there is considerable inter-animal and inter-laboratory variation. We have developed a highly reproducible model of stroke that involves direct electrocoagulation of the MCA in SCID (CB-17/lcr-scid/scidJcl) and CB-17 (CB-17/lcr-+/+Jcl) mice...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space.
Authors: Degracia DJ Abstract The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the second in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. We here build the bistable network model of brain ischemia. The central concept is that of a post-ischemic state space. Ischemia, as a quantitative perturbation, is envisioned...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Towards a dynamical network view of brain ischemia and reperfusion. Part III: therapeutic implications.
Authors: Degracia DJ Abstract The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the third in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. Here the bistable model of brain ischemia is compared to the ischemic cascade concept. The core weakness of the ischemic cascade concept is revealed to be its assumption of sup...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Clinical trial structures.
Authors: Evans SR Abstract Most errors in clinical trials are a result of poor planning. Fancy statistical methods cannot rescue design flaws. Thus careful planning with clear foresight is crucial. The selection of a clinical trial design structure requires logic and creativity. Common structural designs are discussed. PMID: 21423788 [PubMed - as supplied by publisher] (Source: Journal of Experimental Stroke and Translational Medicine)
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Common statistical concerns in clinical trials.
Authors: Evans SR Abstract Statistics are an integral part of clinical trials. Elements of statistics span clinical trial design, data monitoring, analyses, and reporting. A solid understanding of statistical concepts by clinicians improves the comprehension and the resulting quality of clinical trials. This manuscript outlines common statistical concerns in clinical trials that are important for clinicians to understand. PMID: 21423790 [PubMed - as supplied by publisher] (Source: Journal of Experimental Stroke and Translational Medicine)
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Towards a dynamical network view of brain ischemia and reperfusion. Part IV: additional considerations.
Authors: Degracia DJ Abstract The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the fourth in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. Here we consider additional issues to round out and close out this initial presentation of the bistable network view of brain ischemia. Initial considerations of the network a...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Towards a dynamical network view of brain ischemia and reperfusion. Part I: background and preliminaries.
Authors: Degracia DJ Abstract The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the first in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. This first paper sets the stage for developing the bistable model of brain ischemia. Necessary background in network theory is introduced using examples from developmental biol...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Targeting ischemic penumbra Part II: selective drug delivery using liposome technologies.
Authors: Liu S, Levine SR, Winn HR Abstract In the present review (part II), we discuss the challenges and promises of selective drug delivery to ischemic brain tissue by liposome technologies. In part I of this serial review, we proposed "selective drug delivery to ischemic brain tissue" as a technique for neuroprotective treatment of acute ischemic stroke. To be effective, drugs must pass a series of barriers to arrive at ischemic brain. Brain ischemia results in metabolic and structural changes in the ischemic region, which cause additional obstacles for drug delivery. Liposome drug delivery system can...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Strategies for therapeutic hypometabothermia.
Authors: Liu S, Chen JF Abstract Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative conc...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Chemokine receptor-like 2 is involved in ischemic brain injury.
We examined the role of CCRL2 in ischemic brain injury using both in vitro and in vivo mouse stroke models. The expression of CCRL2 was enhanced at both the RNA and protein levels in cultured brain slices under ischemic conditions. Ischemia-induced cell death was reduced in brain slices derived from CCRL2 knockout (KO) mice in comparison with those from wild type (WT) mice. The infarct volume was smaller and neurological deficits were attenuated in CCRL2 KO mice when compared to WT mice subjected to a transient middle cerebral artery occlusion. Our data suggest that CCRL2 is involved in ischemia-induced brain injury in mic...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research

Acute bioenergetic intervention or pharmacological preconditioning protects neuron against ischemic injury.
In this study we have tested the concept of neuron protection by acute bioenergetic intervention or by pharmacological preconditioning with natural antioxidants. Adenosine triphosphate (ATP), pentobarbital, and suramin were encapsulated in pH-sensitive liposomes and used as bioenergy stabilizer. We induced ATP depletion model by incubating cells with media added with ATP-depleting agents for 2 hours. Treatment with bioenergy stabilizer started 10-min post inducing of ATP-depletion. The acute treatment with bioenergy stabilizer significantly increased cell viability in neuro-2a cells. In searching for a pharmacological prec...
Source: Journal of Experimental Stroke and Translational Medicine - December 2, 2015 Category: Neurology Tags: J Exp Stroke Transl Med Source Type: research