GPR39 Agonist TC-G 1008 Promoted Mitochondrial Biogenesis and Improved Antioxidative Capability via CREB/PGC-1 α Pathway Following Intracerebral Hemorrhage in Mice
AbstractMitochondrial dysfunction and excessive reactive oxygen species production due to impaired mitochondrial biogenesis have been proven to exacerbate secondary brain injury after intracerebral hemorrhage (ICH). The G-protein-coupled receptor 39 (GPR39) agonist TC-G 1008 has been shown to exert anti-oxidative stress effect in acute hypoxic brain injury. Herein, our study aimed to investigate the potential effects of TC-G 1008 on neuronal mitochondrial biogenesis and antioxidative stress in a mouse model of ICH and explore the underlying mechanisms. A total of 335 male C57/BL6 mice were used to establish an autologous b...
Source: Translational Stroke Research - March 15, 2024 Category: Neurology Source Type: research

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment
In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) reveal...
Source: Translational Stroke Research - March 15, 2024 Category: Neurology Source Type: research

Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials
AbstractType I interferon (IFN-I) signalling is intricately involved in the pathogenesis of multiple infectious diseases, autoimmune diseases, and neurological diseases. Acute ischemic stroke provokes overactivation of IFN-I signalling within the injured brain, particularly in microglia. Following cerebral ischemia, damage-associated molecular patterns (DAMPs) released from injured neural cells elicit marked proinflammatory episodes within minutes. Among these, self-nucleic acids, including nuclear DNA and mitochondrial DNA (mtDNA), have been recognized as a critical alarm signal to fan the flames of neuroinflammation, pre...
Source: Translational Stroke Research - March 11, 2024 Category: Neurology Source Type: research

Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease
AbstractHypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD.  The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six mont...
Source: Translational Stroke Research - March 5, 2024 Category: Neurology Source Type: research

Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies
In conclusion, this review offers deeper insights into the complex dynamics of SAH and discusses the potential pathways available for advancing its management. (Source: Translational Stroke Research)
Source: Translational Stroke Research - February 29, 2024 Category: Neurology Source Type: research

Similarities in the Electrographic Patterns of Delayed Cerebral Infarction and Brain Death After Aneurysmal and Traumatic Subarachnoid Hemorrhage
AbstractWhile subarachnoid hemorrhage is the second most common hemorrhagic stroke in epidemiologic studies, the recent DISCHARGE-1 trial has shown that in reality, three-quarters of focal brain damage after subarachnoid hemorrhage is ischemic. Two-fifths of these ischemic infarctions occur early and three-fifths are delayed. The vast majority are cortical infarcts whose pathomorphology corresponds to anemic infarcts. Therefore, we propose in this review that subarachnoid hemorrhage as an ischemic-hemorrhagic stroke is rather a third, separate entity in addition to purely ischemic or hemorrhagic strokes. Cumulative focal b...
Source: Translational Stroke Research - February 23, 2024 Category: Neurology Source Type: research

Remote Ischemic Post-conditioning Reduces Cognitive Impairment in Rats Following Subarachnoid Hemorrhage: Possible Involvement in STAT3/STAT5 Phosphorylation and Th17/Treg Cell Homeostasis
This study aims to examine the inhibitory impact of remote ischemic post-conditioning (RIPostC) on the body ’s inflammatory response by regulating Th17/Treg cell homeostasis after SAH. The ultimate goal is to search for potential early treatment targets for SAH. The rat SAH models were made by intravascular puncture of the internal carotid artery. The intervention of RIPostC was administered for three c onsecutive days immediately after successful modeling. Behavioral experiments including the Morris water maze and Y-maze tests were conducted to assess cognitive functions such as spatial memory, working memory, and learn...
Source: Translational Stroke Research - February 15, 2024 Category: Neurology Source Type: research

Switching Off Vascular MAPK Signaling: A Novel Strategy to Prevent Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage
AbstractPatients who initially survive the rupture and repair of a brain aneurysm often take a devastating turn for the worse some days later and die or suffer permanent neurologic deficits. This catastrophic sequela is attributed to a delayed phase of global cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH), but we lack effective treatment. Here we present our view, based on 20  years of research, that the initial drop in blood flow at the time of rupture triggers genomic responses throughout the brain vasculature that manifest days later as increased vasoconstriction and decreased cerebral bloo...
Source: Translational Stroke Research - February 9, 2024 Category: Neurology Source Type: research

Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke
AbstractPerioperative stroke is a devastating complication that occurs during surgery or within 30  days following the surgical procedure. Its prevalence ranges from 0.08 to 10% although it is most likely an underestimation, as sedatives and narcotics can substantially mask symptomatology and clinical presentation. Understanding the underlying pathophysiology and identifying potential therapeuti c targets are of paramount importance. Protease-activated receptors (PARs), a unique family of G-protein-coupled receptors, are widely expressed throughout the human body and play essential roles in various physiological and patho...
Source: Translational Stroke Research - February 7, 2024 Category: Neurology Source Type: research

Correction to: Comparison of Long ‑Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management
(Source: Translational Stroke Research)
Source: Translational Stroke Research - February 6, 2024 Category: Neurology Source Type: research

Angiotensin II Type 2 Receptor Agonism Alleviates Progressive Post-stroke Cognitive Impairment in Aged Spontaneously Hypertensive Rats
This study underscores the importance of translational disease modeling and provides evidence that modulation of t he AT2R signaling via C21 may be a useful therapeutic option to improve sensorimotor and cognitive outcomes even in aged animals. (Source: Translational Stroke Research)
Source: Translational Stroke Research - February 2, 2024 Category: Neurology Source Type: research

Tenecteplase Plus Butyphthalide for Stroke Within 4.5 –6 Hours of Onset (EXIT-BT): a Phase 2 Study
AbstractTo date, the benefit of intravenous thrombolysis is confined to within 4.5  h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25 mg/kg) plus NBP or NBP within 4.5 to 6 h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcom...
Source: Translational Stroke Research - January 19, 2024 Category: Neurology Source Type: research

Glycogen Synthase Kinase-3 β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn
AbstractAdvances in neonatology have significantly reduced mortality rates due to prematurity. However, complications of prematurity have barely changed in recent decades. Germinal matrix-intraventricular hemorrhage (GM-IVH) is one of the most severe complications of prematurity, and these children are prone to suffer short- and long-term sequelae, including cerebral palsy, cognitive and motor impairments, or neuropsychiatric disorders. Nevertheless, GM-IVH has no successful treatment. VP3.15 is a small, heterocyclic molecule of the 5-imino-1,2,4-thiadiazole family with a dual action as a phosphodiesterase 7 and glycogen s...
Source: Translational Stroke Research - January 17, 2024 Category: Neurology Source Type: research

The Role of ICP Monitoring in Minimally Invasive Surgery for the Management of Intracerebral Hemorrhage
AbstractIntracerebral hemorrhage (ICH) is the second major stroke type, with high incidence, high disability rate, and high mortality. At present, there is no effective and reliable treatment for ICH. As a result, most patients have a poor prognosis. Minimally invasive surgery (MIS) is the fastest treatment method to remove hematoma, which is characterized by less trauma and easy operation. Some studies have confirmed the safety of MIS, but there are still no reports showing that it can significantly improve the functional outcome of ICH patients. Intracranial pressure (ICP) monitoring is considered to be an important part...
Source: Translational Stroke Research - December 29, 2023 Category: Neurology Source Type: research

Inhibition of USP30 Promotes Mitophagy by Regulating Ubiquitination of MFN2 by Parkin to Attenuate Early Brain Injury After SAH
This study evaluated the neuroprotective role and possible molecular basis by which inhibiting USP30 to attenuate SAH-induced EBI by promoting neuronal mitophagy. We used an in vitro model of hemoglobin exposure and an in vivo model of intravascular perforation. Increased expression of USP30 was found after SAH in vivo and in vitro, and USP30 inhibition expression in SAH mice treated with MF094 resulted in significant improvement of neurological injury and inflammatory response and mediated good outcomes, suggesting a neuroprotective effect of USP30 inhibition. In cultured neurons, inhibition of USP30 promoted ubiquitinati...
Source: Translational Stroke Research - December 26, 2023 Category: Neurology Source Type: research