Most Promising Approaches to Improve Stroke Outcomes: The Stroke Treatment Academic Industry Roundtable XII Workshop.

The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions.

Use of Botulinum Toxin for Limb Immobilization for Rehabilitation in Rats with Experimental Stroke.

Motor rehabilitation strategies after unilateral stroke suggest that the immobilization of the healthy, unimpaired limb can promote the functional recovery of a paretic limb. In rodents, this has been modeled using casts, harnesses, and other means of restricting the use of the non-paretic forelimb in models of experimental stroke. Here, we evaluated an alternative approach, using botulinum toxin injections to limit the function of the non-paretic forelimb.

Collateral Flow: Prolonging the Ischemic Penumbra.

This editorial serves as an introduction to the Special Issue on Collateral Flow: Prolonging the Ischemic Penumbra

Therapeutic hypothermia for stroke: Unique challenges at the bedside.

Therapeutic hypothermia has shown promise as a means to improving neurological outcomes at several neurological conditions. At the clinical level, it has been shown to improve outcomes in comatose survivors of cardiac arrest and in neonatal hypoxic ischemic encephalopathy, but has yet to be convincingly demonstrated in stroke. While numerous preclinical studies have shown benefit in stroke models, translating this to the clinical level has proven challenging.

Sexual dimorphism in immune cell responses following stroke.

Recent bodies of work in regard to stroke have revealed significant sex differences in terms of risk and outcome. While differences in sex hormones have been the focus of earlier research, the reasons for these differences are much more complex and require further identification. This review covers differences in sex related immune responses with a focus on differences in immune cell composition and function.

Cerebral small vessel disease alters neurovascular unit regulation of microcirculation integrity involved in vascular cognitive impairment.

Cerebral small vessel disease (CSVD) is a generic term used for intracranial vascular disorders caused by the structural changes of cerebral microvessels, including the small arteries, arterioles, capillaries and venules. CSVD exhibits various neuroimaging features and is associated clinical characteristics. Although CSVD is recognized as the leading cause of vascular cognitive impairment (VCI), the underlying mechanism(s) remains elusive.

Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients.

The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients.

Clinical perspectives on ischemic stroke.

Treatments for acute stroke have improved over the past years, but have largely been limited to revascularization strategies. The topic of neuroprotection, or strategies to limit brain tissue damage or even reverse it, has remained elusive. Thus, the clinical mainstays for stroke management have focused on prevention.

Cystatin C is a potential predictor of unfavorable outcomes for cerebral ischemia with intravenous tissue plasminogen activator treatment: A multicenter prospective nested case-control study.

Background And Purpose: The aim of this study was to explore whether cystatin C (CysC) could be used as a potential predictor of clinical outcomes in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA).

Methods: We performed an observational study including a retrospective analysis of data from 125 AIS patients with intravenous thrombolysis. General linear models were applied to compare CysC levels between groups with different outcomes; logistic regression analysis and receiver-operating characteristic curves were adopted to identify the association between CysC and the therapeutic effects.

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

Objective: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC).

Methods: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks.

Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury.

The 70 kDa heat shock protein (HSP70) is a stress-inducible protein that has been shown to protect the brain from various nervous system injuries. It allows cells to withstand potentially lethal insults through its chaperone functions. Its chaperone properties can assist in protein folding and prevent protein aggregation following several of these insults.

Vascular, inflammatory and metabolic risk factors in relation to dementia in Parkinson's disease patients with type 2 diabetes mellitus.

There are limited data on vascular, inflammatory, metabolic risk factors of dementia in Parkinson's disease (PD) with type 2 diabetes mellitus (DM) (PD-DM). In a study of 928 subjects comprising of 215 PD with DM (including 31 PD-DM with dementia, PD-DMD), 341 PD without DM (including 31 PD with dementia, PDD) and 372 DM without PD (including 35 DM with dementia, DMD) patients, we investigated if vascular, inflammatory, metabolic, and magnetic resonance imaging (MRI) markers were associated with dementia in PD-DM. Lower fasting blood glucose (FBG<5mmol/L, OR=4.

Cofilin-actin rod formation in experimental stroke is attenuated by therapeutic hypothermia and overexpression of the inducible 70 kD inducible heat shock protein (Hsp70).

Background And Purpose: Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin. Under ischemic conditions, these rods have been observed in neuronal dendrites and axons and may contribute to the loss of these processes. Hypothermia (Hypo) and the 70 kD inducible heat shock protein (Hsp70) are both known to improve outcomes after stroke, but the mechanisms are uncertain.

Heat shock protein signaling in brain ischemia and injury.

Heat shock proteins (HSPs) are chaperones that catalyze the refolding of denatured proteins. In addition to their ability to prevent protein denaturation and aggregation, the HSPs have also been shown to modulate many signaling pathways. Among HSPs, the inducible 70 kDa HSP (HSP70) has especially been shown to improve neurological outcome in experimental models of brain ischemia and injury.

Models of poststroke depression and assessments of core depressive symptoms in rodents: How to choose?

Our previous studies have indicated that depression and declined cognition have been involved in some neurodegenerative diseases including Stroke, Parkinson's diseases and Vascular Parkinsonism. Post-stroke depression (PSD) is the most common psychiatric disorder following a stroke and has high morbidity and mortality. Studies on PSD are increasingly common, but the specific mechanisms remain unknown.

The role of NOX inhibitors in neurodegenerative diseases.

Oxidative stress is a key player in both chronic and acute brain disease due to the higher metabolic demand of the brain. Among the producers of free radicals, NADPH-oxidase (NOX) is a major contributor to oxidative stress in neurological disorders. In the brain, the superoxide produced by NOX is mainly found in leukocytes.

Plasma Lipoprotein-associated Phospholipase A2 and Superoxide Dismutase are Independent Predicators of Cognitive Impairment in Cerebral Small Vessel Disease Patients: Diagnosis and Assessment.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and superoxide dismutase (SOD) are linked to regulating vascular/neuro-inflammation and stroke. Using a retrospective design, we investigated whether circulating Lp-PLA2 and SOD in cerebral small vessel disease (CSVD) patients were associated with cognitive impairment. Eighty-seven CSVD patients were recruited.

Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease.

Therapeutic hypothermia has consistently been shown to be a robust neuroprotectant in many labs studying different models of neurological disease. Although this therapy has shown great promise, there are still challenges at the clinical level that limit the ability to apply this routinely to each pathological condition. In order to overcome issues involved in hypothermia therapy, understanding of this attractive therapy is needed.

Triggering receptor expressed on myeloid cells-2 expression in the brain is required for maximal phagocytic activity and improved neurological outcomes following experimental stroke.

Triggering receptor expressed on myeloid cells-2 (TREM2) is an innate immune receptor that promotes phagocytosis by myeloid cells such as microglia and macrophages. We previously showed that TREM2 deficiency worsened outcomes from experimental stroke and impeded phagocytosis. However, myeloid cells participating in stroke pathology include both brain resident microglia and circulating macrophages.

Microglial Calcium Release-Activated Calcium Channel Inhibition Improves Outcome from Experimental Traumatic Brain Injury and Microglia-Induced Neuronal Death.

Store-operated Ca entry (SOCE) mediated by calcium release-activated calcium (CRAC) channels contributes to calcium signaling. The resulting intracellular calcium increases activate calcineurin, which in turn activates immune transcription factor nuclear factor of activated T cells (NFAT). Microglia contain CRAC channels, but little is known whether these channels play a role in acute brain insults.

The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke.

The 70-kDa heat shock protein (Hsp70) is a cytosolic chaperone which facilitates protein folding, degradation, complex assembly, and translocation. Following stroke, these functions have the potential to lead to cytoprotection, and this has been demonstrated using genetic mutant models, direct gene transfer or the induction of Hsp70 via heat stress, approaches which limit its translational utility. Recently, the investigation of Hsp70-inducing pharmacological compounds, which, through their ability to inhibit Hsp90, has obvious clinical implications in terms of potential therapies to mitigate cell death and inflammation, and lead to neuroprotection from brain injury.