ATG5 Knockdown Attenuates Ischemia ‒Reperfusion Injury by Reducing Excessive Autophagy-Induced Ferroptosis
AbstractAutophagy has been described to be both protective and pathogenic in cerebral ischemia/reperfusion (I/R) injury. The underlying association between autophagy and ferroptosis in ischemic stroke has not yet been clearly investigated. The purpose of this study was to explore the role of autophagy-related gene 5 (ATG5) in experimental ischemic stroke. After injection of ATG5 shRNA lentivirus, mice underwent surgery for transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. The infarct volume, neurological function, apoptosis, reactive oxygen species (ROS), autophagy, and ferroptosis levels w...
Source: Translational Stroke Research - December 16, 2022 Category: Neurology Source Type: research
Correction to: Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke
(Source: Translational Stroke Research)
Source: Translational Stroke Research - December 16, 2022 Category: Neurology Source Type: research
Recombinant Human Perlecan DV and Its LG3 Subdomain Are Neuroprotective and Acutely Functionally Restorative in Severe Experimental Ischemic Stroke
AbstractDespite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDVLG3), a 21-kDa C-terminal subdomain of rhPDV, has been demonstrated to more avidly bind to the α2β1 integrin receptor than its parent molecule and consequently was postulated to evok...
Source: Translational Stroke Research - December 12, 2022 Category: Neurology Source Type: research
Apolipoprotein E ɛ2 Is Associated with the White Matter Hyperintensity Multispot Pattern in Spontaneous Intracerebral Hemorrhage
AbstractThe white matter hyperintensity (WMH) multispot pattern, as multiple punctate subcortical foci, could differentiate cerebral amyloid angiopathy (CAA) from hypertensive arteriolopathy. Nevertheless, the pathophysiology underlying the multispot sign is still inexplicit. We aimed to explore risk factors for multispot patterns in cerebral small vessel disease (CSVD) –related intracerebral hemorrhage (ICH). Between June 2018 and January 2020, we retrospectively rated the WMH multispot pattern while blinded to our prospective spontaneous ICH cohort’s clinical data. Demographic, genetic, and neuroimaging characteristi...
Source: Translational Stroke Research - December 10, 2022 Category: Neurology Source Type: research
Association of Gut Microbiome with Early Brain Injury After Subarachnoid Hemorrhage: an Experimental Study
AbstractThe occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2 weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting bloo...
Source: Translational Stroke Research - December 9, 2022 Category: Neurology Source Type: research
Translational Molecular Imaging Tool of Vulnerable Carotid Plaque: Evaluate Effects of Statin Therapy on Plaque Inflammation and American Heart Association –Defined Risk Levels in Cuff-Implanted Apolipoprotein E–Deficient Mice
AbstractIdentification of high-risk carotid plaques in asymptomatic patients remains a challenging but crucial step in stroke prevention. The challenge is to accurately monitor the development of high-risk carotid plaques and promptly identify patients, who are unresponsive to best medical therapy, and hence targeted for carotid surgical interventions to prevent stroke. Inflammation is a key operator in destabilisation of plaques prior to clinical sequelae. Currently, there is a lack of imaging tool in routine clinical practice, which allows assessment of inflammatory activity within the atherosclerotic plaque. Herein, we ...
Source: Translational Stroke Research - December 9, 2022 Category: Neurology Source Type: research
Stroke and Neurogenesis: Bridging Clinical Observations to New Mechanistic Insights from Animal Models
AbstractStroke was the 2nd leading cause of death and a major cause of morbidity. Unfortunately, there are limited means to promote neurological recovery post-stroke, but research has unearthed potential targets for therapies to encourage post-stroke neurogenesis and neuroplasticity. The occurrence of neurogenesis in adult mammalian brains, including humans, was not widely accepted until the 1990s. Now, adult neurogenesis has been extensively studied in human and mouse neurogenic brain niches, of which the subventricular zone of the lateral ventricles and subgranular zone of the dentate gyrus are best studied. Numerous oth...
Source: Translational Stroke Research - December 3, 2022 Category: Neurology Source Type: research
Effects of the New Thrombolytic Compound LT3001 on Acute Brain Tissue Damage After Focal Embolic Stroke in Rats
In this study, we tested the effects of LT3001 as a potential alternative thrombolytic in focal embolic ischemic stroke rat model. Stroked rats received intravenous injection of 10 mg/kg LT3001 or tPA at 1.5, 3, or 4.5 h after stroke, respectively, and the outcomes were measured at different time points after stroke by performing multi-parametric MRI, 2,3,5-triphenyltetrazolium chloride (TTC) staining, and modified neurological severity score. Lastly, we assessed the effect of LT3001 on the tPA activity in vitro, the international normalized ratio (INR), and the serum levels of active tPA and plasminogen activator inhib...
Source: Translational Stroke Research - November 29, 2022 Category: Neurology Source Type: research
Remote Ischemic Conditioning Enhances Collateral Circulation Through Leptomeningeal Anastomosis and Diminishes Early Ischemic Lesions and Infarct Volume in Middle Cerebral Artery Occlusion
AbstractRemote ischemic conditioning (RIC) has attracted much attention as a protective strategy for the heart and brain, although the underlying mechanisms remain unclear. We hypothesized that RIC enhances collateral circulation during cerebral ischemia through endothelial function and mitigates both early ischemic change and final infarct volume. We tested the RIC and sham procedure 30 min after permanent middle cerebral artery occlusion (MCAO) in male mice. Collateral circulation was examined during the procedure with 2D color-coded ultrasound imaging. Immediately after four cycles of RIC, early ischemic lesions on ma...
Source: Translational Stroke Research - November 28, 2022 Category: Neurology Source Type: research
Long Non-coding RNA H19 Promotes NLRP3-Mediated Pyroptosis After Subarachnoid Hemorrhage in Rats
Abstract NLRP3 inflammasomes have been reported to be an essential mediator in the inflammatory response during early brain injury (EBI) following subarachnoid hemorrhage (SAH). Recent studies have indicated that NLRP3 inflammasome-mediated pyroptosis and long non-coding RNA (lncRNA) H19 can participate in the inflammatory response. However, the roles and functions of lncRNA H19 in NLRP3 inflammasome-mediated pyroptosis during EBI after SAH are unknown and need to be further elucidated. NLRP3 inflammasome proteins were significantly elevated in CSF of human with SAH induced EBI and presented a positive correlation with s...
Source: Translational Stroke Research - November 24, 2022 Category: Neurology Source Type: research
Meta-review on Perforation Model of Subarachnoid Hemorrhage in Mice: Filament Material as a Possible Moderator of Mortality
AbstractRobust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databasesPubMed,Embase, andWeb of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were incl...
Source: Translational Stroke Research - November 23, 2022 Category: Neurology Source Type: research
Aerobic Glycolysis Induced by mTOR/HIF-1 α Promotes Early Brain Injury After Subarachnoid Hemorrhage via Activating M1 Microglia
In conclusion, the present study showed new evidence that aerobic glycolysis induced by mTOR/HIF-1 α might promote EBI after SAH by activating M1 microglia. This finding provided new insights for the treatment of EBI. (Source: Translational Stroke Research)
Source: Translational Stroke Research - November 17, 2022 Category: Neurology Source Type: research
Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke
AbstractIschemic stroke presents a major global economic and public health burden. Although recent advances in available endovascular therapies show improved functional outcome, a good number of stroke patients are either ineligible or do not have access to these treatments. Also, robust collateral flow during acute ischemic stroke independently predicts the success of endovascular therapies and the outcome of stroke. Hence, adjunctive therapies for cerebral blood flow (CBF) enhancement are urgently needed. A very clear overview of the pial collaterals and the role of genetics are presented in this review. We review availa...
Source: Translational Stroke Research - November 17, 2022 Category: Neurology Source Type: research
Revisiting Transcranial Light Stimulation as a Stroke Therapeutic —Hurdles and Opportunities
AbstractNear-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the e...
Source: Translational Stroke Research - November 12, 2022 Category: Neurology Source Type: research
Intracranial Pressure Dysfunction Following Severe Intracerebral Hemorrhage in Middle-Aged Rats
AbstractRising intracranial pressure (ICP) aggravates secondary injury and heightens risk of death following intracerebral hemorrhage (ICH). Long-recognized compensatory mechanisms that lower ICP include reduced cerebrospinal fluid and venous blood volumes. Recently, we identified another compensatory mechanism in severe stroke, a decrease in cerebral parenchymal volume via widespread reductions in cell volume and extracellular space (tissue compliance). Here, we examined how age affects tissue compliance and ICP dynamics after severe ICH in rats (collagenase model). A planned comparison to historical young animal data rev...
Source: Translational Stroke Research - November 11, 2022 Category: Neurology Source Type: research
