Multinuclear MRI Reveals Early Efficacy of Stem Cell Therapy in Stroke
AbstractCompromised adult human mesenchymal stem cells (hMSC) can impair cell therapy efficacy and further reverse ischemic recovery. However, in vitro assays require extended passage to characterize cells, limiting rapid assessment for therapeutic potency. Multinuclear magnetic resonance imaging and spectroscopy (MRI/S) provides near real-time feedback on disease progression and tissue recovery. Applied to ischemic stroke,23Na MRI evaluates treatment efficacy within 24  h after middle cerebral artery occlusion, showing recovery of sodium homeostasis and lesion reduction in specimens treated with hMSC while1H MRS identifi...
Source: Translational Stroke Research - July 28, 2022 Category: Neurology Source Type: research

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA
In conclusion, patients with aSAH have high post-operative complication ra tes and costs. Development of novel interventions to reduce complications and improve outcomes is crucial. (Source: Translational Stroke Research)
Source: Translational Stroke Research - July 26, 2022 Category: Neurology Source Type: research

Significance of Microglial Energy Metabolism in Maintaining Brain Homeostasis
(Source: Translational Stroke Research)
Source: Translational Stroke Research - July 26, 2022 Category: Neurology Source Type: research

Collateral-Core Ratio as a Novel Predictor of Clinical Outcomes in Acute Ischemic Stroke
AbstractThe interaction effect between collateral circulation and ischemic core size on stroke outcomes has been highlighted in acute ischemic stroke (AIS). However, biomarkers that assess the magnitude of this interaction are still lacking. We aimed to present a new imaging marker, the collateral-core ratio (CCR), to quantify the interaction effect between these factors and evaluate its ability to predict functional outcomes using machine learning (ML) in AIS. Patients with AIS caused by anterior circulation large vessel occlusion (LVO) were recruited from a prospective multicenter study. CCR was calculated as collateral ...
Source: Translational Stroke Research - July 25, 2022 Category: Neurology Source Type: research

rs2253820 Variant Controls Blood Pressure Dip After Stroke by Increasing CLOCK –BMAL1 Expression
AbstractCircadian rhythm (CR) disturbances are associated with the development of cardiovascular diseases, including stroke. The central clock in the brain, which is maintained by circadian genes, maintains the daily rhythm according to the external environment. Here, we aimed to probe the interaction between the PER1rs2253820 variant and blood pressure dip (BPD) status and mechanisms. We studied spontaneously hypertensive rats (SHR) with transient middle cerebral artery occlusion (SHR-tMCAO). The mutation site of PER1 was identified using bioinformatics analysis, followed by RT-qPCR and western blot validation. SHR-tMCAO ...
Source: Translational Stroke Research - July 23, 2022 Category: Neurology Source Type: research

Three Days Delayed Recanalization Improved Neurological Function in pMCAO Rats by Increasing M2 Microglia —Possible Involvement of the IL-4R/STAT6/PPARγ Pathway
AbstractCurrent approved therapies for acute ischemic stroke have a restricted therapeutic time window. Delayed recanalization, which has been utilized clinically in patients who have missed the time window for administration, may be a promising alternative for stroke patients. However, the underlying molecular mechanisms remain undiscovered. Herein, we hypothesized that delayed recanalization would increase M2 microglial polarization through the IL-4R (interleukin-4 receptor)/STAT6 (signal transducer and activators of transcription 6)/PPAR γ (peroxisome proliferator–activated receptor γ) pathway, subsequently promotin...
Source: Translational Stroke Research - July 22, 2022 Category: Neurology Source Type: research

Recurrent Transient Ischemic Attack Induces Neural Cytoskeleton Modification and Gliosis in an Experimental Model
AbstractTransient ischemic attack (TIA) presents a high risk for subsequent stroke, Alzheimer ’s disease (AD), and related dementia (ADRD). However, the neuropathophysiology of TIA has been rarely studied. By evaluating recurrent TIA-induced neuropathological changes, our study aimed to explore the potential mechanisms underlying the contribution of TIA to ADRD. In the current study, we es tablished a recurrent TIA model by three times 10-min middle cerebral artery occlusion within a week in rat. Neither permanent neurological deficit nor apoptosis was observed following recurrent TIA. No increase of AD-related biomarker...
Source: Translational Stroke Research - July 22, 2022 Category: Neurology Source Type: research

Metformin Alleviates Delayed Hydrocephalus after Intraventricular Hemorrhage by Inhibiting Inflammation and Fibrosis
In conclusion, metformin attenuated neuroinflammation and subsequent fibrosis after IVH by regulating AMPK /SIRT1/ NF-κB pathways, thereby reducing delayed hydrocephalus. Metformin may be a promising therapeutic agent to prevent delayed hydrocephalus following IVH. (Source: Translational Stroke Research)
Source: Translational Stroke Research - July 19, 2022 Category: Neurology Source Type: research

Development of Molecular Magnetic Resonance Imaging Tools for Longitudinal Tracking of Carotid Atherosclerotic Disease Using Fast Imaging with Steady-State Precession
AbstractIdentification of patients with high-risk asymptomatic carotid plaques remains a challenging but essential step in stroke prevention. Current selection criteria for intervention in carotid disease are still determined by symptomatology and degree of luminal stenosis. This strategy has been less effective in identifying the high-risk asymptomatic individual patients. Inflammation is the key factor that drives plaque instability causing clinical sequelae. Currently, there is no imaging tool in routine clinical practice to assess the inflammatory status within atherosclerotic plaques. Herein we describe the developmen...
Source: Translational Stroke Research - July 18, 2022 Category: Neurology Source Type: research

Sustained ICP Elevation Is a Driver of Spatial Memory Deficits After Intraventricular Hemorrhage and Leads to Activation of Distinct Microglial Signaling Pathways
In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH  + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most s...
Source: Translational Stroke Research - July 12, 2022 Category: Neurology Source Type: research

NLRP3 Inflammasome Overactivation in Patients with Aneurysmal Subarachnoid Hemorrhage
AbstractAneurysmal subarachnoid hemorrhage (aSAH) is an uncommon and severe subtype of stroke leading to the loss of many years of productive life. We analyzed NLRP3 activity as well as key components of the inflammasome cascade in monocytes and plasma from 28 patients with aSAH and 14 normal controls using flow cytometry, western blot, ELISA, and qPCR technologies. Our data reveal that monocytes from patients with aSAH present an overactivation of the NLRP3 inflammasome, which results in the presence of high plasma levels of interleukin (IL)-1 β, IL-18, gasdermin D, and tissue factor. Although further research is needed,...
Source: Translational Stroke Research - July 11, 2022 Category: Neurology Source Type: research

Circulating Plasma miRNA Homologs in Mice and Humans Reflect Familial Cerebral Cavernous Malformation Disease
AbstractPatients with familial cerebral cavernous malformation (CCM) inherit germline loss of function mutations and are susceptible to progressive development of brain lesions and neurological sequelae during their lifetime. To date, no homologous circulating molecules have been identified that can reflect the presence of germ line pathogenetic CCM mutations, either in animal models or patients. We hypothesize that homologous differentially expressed (DE) plasma miRNAs can reflect the CCM germline mutation in preclinical murine models and patients. Herein, homologous DE plasma miRNAs with mechanistic putative gene targets...
Source: Translational Stroke Research - June 17, 2022 Category: Neurology Source Type: research

Collateral Blood Flow and Ischemic Core Growth
AbstractTreatment of a large vessel occlusion in the acute ischemic stroke setting focuses on vessel recanalization, and endovascular thrombectomy results in favorable outcomes in appropriate candidates. Expeditious treatment is imperative, but patients often present to institutions that do not have neurointerventional surgeons and need to be transferred to a comprehensive stroke center. These treatment delays are common, and it is important to identify factors that mitigate the progression of the ischemic core in order to maximize the preservation of salvageable brain tissue. Collateral blood flow is the strongest factor ...
Source: Translational Stroke Research - June 14, 2022 Category: Neurology Source Type: research

Genome-Wide Association Study of Intracranial Artery Stenosis Followed by Phenome-Wide Association Study
AbstractThe genetic background of intracranial artery stenosis (ICAS), a major cause of ischemic stroke, remains elusive. We performed the world ’s first genome-wide association study (GWAS) of ICAS using DNA samples from Japanese subjects, to identify the genetic factors associated with ICAS and their correlation with clinical features. We also conducted a phenome-wide association study (PheWAS) of the top variant identified via GWAS to d etermine its association with systemic disease. The GWAS involved 408 patients with ICAS and 349 healthy controls and utilized an Asian Screening Array of venous blood samples. The Phe...
Source: Translational Stroke Research - June 14, 2022 Category: Neurology Source Type: research

LncRNAs: Promising Therapeutic Targets and Biomarkers for Ischemic Stroke
AbstractIschemic stroke is one of the leading causes of mortality and disability worldwide. Currently, options for ischemic stroke clinical therapy remain limited to intravenous thrombolysis and thrombectomy, which can only be applied to a minority of patients due to narrow therapeutic time window. Therefore, the discovery of new therapeutic targets and biomarkers is of great significance for ischemic stroke therapy. Long non-coding RNAs (lncRNAs) are the most extensive ncRNA transcripts and play critical roles in different kinds of diseases. Accumulative evidence suggests that lncRNAs are widely involved in multiple patho...
Source: Translational Stroke Research - June 13, 2022 Category: Neurology Source Type: research