Intracerebral Administration of a Novel Self-Assembling Peptide Hydrogel Is Safe and Supports Cell Proliferation in Experimental Intracerebral Haemorrhage
AbstractIntracerebral haemorrhage (ICH) is the deadliest form of stroke, but current treatment options are limited, meaning ICH survivors are often left with life-changing disabilities. The significant unmet clinical need and socioeconomic burden of ICH mean novel regenerative medicine approaches are gaining interest. To facilitate the regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In this paper, the objective was to explore whether injection of a novel self-assembling peptide hydrogel (SAPH) Alpha2 ...
Source: Translational Stroke Research - October 18, 2023 Category: Neurology Source Type: research
Mesenchymal Stem Cells Overexpressing FGF21 Preserve Blood-Brain Barrier Integrity in Experimental Ischemic Stroke
In this study, we assessed the effects of transplantation of MSCs overexpressing FGF21 (MSCs-FGF21) on ischemia-induced neurological deficits and BBB breakdown. MSCs-FGF21 was injected into the rat brain via the intracerebroventricular route 24 h after middle cerebral artery occlusion (MCAO) surgery. The behavioral performance was assessed using modified neurological severity scores and Y-maze tests. BBB disruption was measured using Evans blue staining, IgG extravasation, and brain water content. The levels of tight junction proteins, aquaporin 4, and neuroinflammatory markers were analyzed by western blotting and immunoh...
Source: Translational Stroke Research - October 3, 2023 Category: Neurology Source Type: research
Sirtuins as Potential Targets for Neuroprotection: Mechanisms of Early Brain Injury Induced by Subarachnoid Hemorrhage
AbstractSubarachnoid hemorrhage (SAH) is a prevalent cerebrovascular disease with significant global mortality and morbidity rates. Despite advancements in pharmacological and surgical approaches, the quality of life for SAH survivors has not shown substantial improvement. Traditionally, vasospasm has been considered a primary contributor to death and disability following SAH, but anti-vasospastic therapies have not demonstrated significant benefits for SAH patients' prognosis. Emerging studies suggest that early brain injury (EBI) may play a crucial role in influencing SAH prognosis. Sirtuins (SIRTs), a group of NAD  +â...
Source: Translational Stroke Research - October 2, 2023 Category: Neurology Source Type: research
Comparison of Long-Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management
This study examines the long-term effectiveness of interventional therapy versus conservative management in reducing hemorrhagic stroke or death in patients with ruptured diffuse AVMs. The analysis was conducted based on a multi-institutional database in China. Patients were divided into two groups: conservative management and interventional therapy. Using propensity score matching, patients were compared for the primary outcome of hemorrhagic stroke or death and the secondary outcomes of disability and neurofunctional decline. Out of 4286 consecutive AVMs in the registry, 901 patients were eligible. After matching, 70 pai...
Source: Translational Stroke Research - September 30, 2023 Category: Neurology Source Type: research
Difference in Clinical Phenotype, Mutation Position, and Structural Change of RNF213 Rare Variants Between Pediatric and Adult Japanese Patients with Moyamoya Disease
This study included 151 Japanese patients with MMD. After performing targeted resequencing for all coding exons inRNF213, we investigated the clinical phenotype and statistically analyzed the genotype –phenotype correlation. We mappedRNF213 variants on a three-dimensional (3D) model of human RNF213 and analyzed the structural changes due to variants. TheRNF213 p.R4810K homozygous variant, p.R4810K heterozygous variant, and wild type were detected in 10 (6.6%), 111 (73.5%), and 30 (19.9%) MMD patients, respectively. In addition, 15 rare variants were detected in 16 (10.6%) patients. In addition to the influence of the p.R...
Source: Translational Stroke Research - September 28, 2023 Category: Neurology Source Type: research
Identification of Non-excitatory Amino Acids and Transporters Mediating the Irreversible Synaptic Silencing After Hypoxia
AbstractThe contribution of excitatory amino acids (AA) to ischemic brain injury has been widely described. In addition, we reported that a mixture of non-excitatory AA at plasmatic concentrations turns irreversible the depression of synaptic transmission caused by hypoxia. Here, we describe that the presence of seven non-excitatory AA (L-alanine, L-glutamine, glycine, L-histidine, L-serine, taurine, and L-threonine) during hypoxia provokes an irreversible neuronal membrane depolarization, after an initial phase of hyperpolarization. The collapse of the membrane potential correlates with a great increase in fiber volley am...
Source: Translational Stroke Research - September 27, 2023 Category: Neurology Source Type: research
Treatment of Stroke at a Delayed Timepoint with a Repurposed Drug Targeting Sigma 1 Receptors
In this study, we hypothesized that oral oxeladin citrate would stimulate BDNF secretion and improve stroke outcomes when administered to male rats starting 48 Â h after transient middle cerebral artery occlusion. Oxeladin did not alter blood clotting and crossed the blood brain barrier within 30Â min of oral administration. Rats underwent 90Â min of transient middle cerebral artery occlusion. Forty-eight hours later rats began receiving daily oxeladin (13 5Â mg/kg) for 11Â days. Oxeladin significantly improved neurological function on days 3, 7, and 14 following MCAO. Infarct size was not altered by a single dose, but the...
Source: Translational Stroke Research - September 13, 2023 Category: Neurology Source Type: research
Statins may Decrease Aneurysm wall Enhancement of Unruptured Fusiform Intracranial Aneurysms: A high-resolution 3T MRI Study
AbstractInflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms. Aneurysm wall enhancement (AWE) in high-resolution magnetic resonance imaging (HR-MRI) has emerged as a surrogate biomarker of vessel wall inflammation and unruptured intracranial aneurysm instability. We investigated the correlation between anti-inflammatory drug use and three-dimensional AWE of fusiform intracranial aneurysms (FIAs). We retrospectively analyzed consecutive patients with FIAs in our database who underwent 3T HR-MRI at three Chinese centers. FIAs were classified as fusiform...
Source: Translational Stroke Research - September 7, 2023 Category: Neurology Source Type: research
Prognostic Value of Venous Outflow Profiles on Multiphase CT Angiography for the Patients with Acute Ischemic Stroke After Endovascular Thrombectomy
This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT. (Source: Translational Stroke Research)
Source: Translational Stroke Research - September 5, 2023 Category: Neurology Source Type: research
Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm
AbstractIntracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subs...
Source: Translational Stroke Research - August 30, 2023 Category: Neurology Source Type: research
Potential Targets for the Treatment of Brain Arteriovenous Malformations
(Source: Translational Stroke Research)
Source: Translational Stroke Research - August 23, 2023 Category: Neurology Source Type: research
A Transcriptomic Comparative Study of Cranial Vasculature
We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed...
Source: Translational Stroke Research - August 23, 2023 Category: Neurology Source Type: research
Factors Influencing Collateral Circulation Formation After Indirect Revascularization for Moyamoya Disease: a Narrative Review
This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease. (Source: Translational Stroke Research)
Source: Translational Stroke Research - August 17, 2023 Category: Neurology Source Type: research
Deferoxamine Therapy for Hemorrhagic Transformation Following Brain Ischemia
(Source: Translational Stroke Research)
Source: Translational Stroke Research - August 17, 2023 Category: Neurology Source Type: research
Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke
Abstractp53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynami...
Source: Translational Stroke Research - August 15, 2023 Category: Neurology Source Type: research
