Basigin in cerebrovascular diseases: roles, mechanisms, and therapeutic target potential.

Cerebrovascular diseases are major global health issues, responsible for significant morbidity and mortality. Basigin (additionally called CD147 or EMMPRIN) is a glycosylated transmembrane protein that facilitates intercellular communication. Recent research has highlighted the critical role of Basigin in inducing matrix metalloproteinases (MMPs), which contribute to the progression of cerebrovascular diseases.

Snake venom weakens neurovascular integrity and promotes vulnerability to neuroinflammation.

Snake envenomation poses significant medical challenges, particularly in subtropical and tropical regions, with long-term impacts on neurovascular integrity and neuroinflammation remaining underexplored. This study investigates the effects of venom from four species of venomous snakes in southern China-Zhoushan Cobra (Naja atra, NA), Many-banded Krait (Bungarus multicinctus, BM), Five-paced Pit Viper (Deinagkistrodon acutus, DA), and Chinese Moccasin (Protobothrops mucrosquamatus, PM) - on the blood-brain barrier (BBB) and chronic neuroinflammation. Using mass spectrometry, we analyzed venom protein compositions, while cytotoxic effects on mouse brain endothelial cells (bEND.

Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms.

Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate relationship between obesity and BBB dysfunction, elucidating the underlying phenotypes and molecular mechanisms. We commence with an overview of the BBB's critical role in maintaining cerebral homeostasis and the pathological alterations induced by obesity.

Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization.

An MMP-9 exclusive neutralizing antibody attenuates blood-brain barrier breakdown in mice with stroke and reduces stroke patient-derived MMP-9 activity.

Rapid upregulation of matrix metalloproteinase 9 (MMP-9) leads to blood-brain barrier (BBB) breakdown following stroke, but no MMP-9 inhibitors have been approved in clinic largely due to their low specificities and side effects. Here, we explored the therapeutic potential of a human IgG monoclonal antibody (mAb), L13, which was recently developed with exclusive neutralizing specificity to MMP-9, nanomolar potency, and biological function, using mouse stroke models and stroke patient samples. We found that L13 treatment at the onset of reperfusion following cerebral ischemia or after intracranial hemorrhage (ICH) significantly reduced brain tissue injury and improved the neurological outcomes of mice.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear.

Spatiotemporal lipidomics reveals key features of brain lipid dynamic changes after cerebral ischemia and reperfusion therapy.

Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely reperfusion therapy. It remains unclear how reperfusion therapy results in secondary injury to the brain tissue and whether different reperfusion therapies induce differential effects.

Comparative Metabolomics Analysis Reveals Key Metabolic Mechanisms and Protein Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases, accompanied by global alterations in metabolic profiles. In the past 10 years, over hundreds of metabolomics studies have been conducted to unravel metabolic changes in AD, which provides insight into the identification of potential biomarkers for diagnosis, treatment, and prognostic assessment. However, since different species may lead to systemic abnormalities in metabolomic profiles, it is urgently needed to perform a comparative metabolomics analysis between AD animal models and human patients.

Activation of Wnt/Beta-Catenin Signaling Pathway as a Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury.

Stroke is one of the leading causes of mortality, and survivors experience serious neurological and motor behavioral deficiencies. Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur because of ischemia/reperfusion injury. Wnt signaling is an evolutionarily conserved signaling pathway that has been manifested to play a key role in embryo development and function maintenance in adults.

Lithium attenuates blood-brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β-catenin signaling-dependent mechanism in mice.

Background: Vasogenic cerebral edema resulting from blood-brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β-catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β-catenin signaling.

The Role of Immune Cells in Post-Stroke Angiogenesis and Neuronal Remodeling: The Known and the Unknown.

Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur due to ischemia-induced cerebral pathology. Mounting evidence indicates that the robust recruitment of immune cells plays a central role in the acute stage of stroke. Infiltrating peripheral immune cells and resident microglia mediate neuronal cell death and blood-brain barrier disruption by releasing inflammation-associated molecules.

Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke.

Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed.

The tissue origin of human mesenchymal stem cells dictates their therapeutic efficacy on glucose and lipid metabolic disorders in type II diabetic mice.

Background: The therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton's jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice.

Methods: Fourteen-to-fifteen-week-old male C57BL/6 db/db mice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks.

Inhibition of hypoxia inducible factor 1 by YC-1 attenuates tissue plasminogen activator induced hemorrhagic transformation by suppressing HMGB1/TLR4/NF-κB mediated neutrophil infiltration in thromboembolic stroke rats.

Hemorrhagic transformation (HT) is a frequent complication of ischemic stroke after thrombolytic therapy and seriously affects the prognosis of stroke. Due to the limited therapeutic window and hemorrhagic complications, tissue plasminogen activator (t-PA) is underutilized in acute ischemic stroke. Currently, there are no clinically effective drugs to decrease the incidence of t-PA-induced HT.

Lithium alleviates blood-brain barrier breakdown after cerebral ischemia and reperfusion by upregulating endothelial Wnt/β-catenin signaling in mice.

Although upregulation of endothelial Wnt/β-catenin signaling may be used to treat blood-brain barrier (BBB) breakdown caused by cerebral ischemia/reperfusion injury, no agents based on this mechanism are available clinically. Lithium, a medication used for treating bipolar mood disorders, upregulates Wnt/β-catenin signaling, but whether lithium alleviates BBB breakdown after ischemic stroke by upregulating endothelial Wnt/β-catenin signaling is unclear. Here, we evaluated the BBB-protective effect of lithium in adult mice with 1-h middle cerebral artery occlusion and 48-h reperfusion (MCAO/R) by determining neurological outcomes, BBB function and related molecular components.

Pinocembrin Protects Blood-Brain Barrier Function and Expands the Therapeutic Time Window for Tissue-Type Plasminogen Activator Treatment in a Rat Thromboembolic Stroke Model.

Tissue-type plasminogen activator (t-PA) remains the only approved therapy for acute ischemic stroke but has a restrictive treatment time window of 4.5 hr. Prolonged ischemia causes blood-brain barrier (BBB) damage and increases the incidence of hemorrhagic transformation (HT) secondary to reperfusion.

Claulansine F promoted the neuronal differentiation of neural stem and progenitor cells through Akt/GSK-3β/β-catenin pathway.

The persistence of neurogenesis raises the idea that neurons produced by the resident or transplanted neural stem cells could replace the neurons lost from brain injury or neurodegenerative disease. Therefore, compounds or methods for promoting neuronal differentiation become the focus of neurodegenerative disease therapy research. Claulansine F (Clau F), a newly discovered carbazole alkaloid, has been showed to induce neuritogenesis in PC12 cells.

Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat embolic stroke model.

The treatment of acute ischemic stroke (AIS) using thrombolysis with recombinant tissue-plasminogen activator (rtPA, alteplase) is limited by its narrow time window and the risk of hemorrhage. Recombinant plasminogen activator (rPA, reteplase) has been used clinically on coronary artery thrombosis and acute myocardial infarction. It is necessary to induce strokes experimentally as a means of validating the rPA timing on patients with AIS.

A novel embolic middle cerebral artery occlusion model induced by thrombus formed in common carotid artery in rat.

Stroke is a major cause of death and disability worldwide. However, treatment options to date are very limited. To meet the need for validating the novel therapeutic approaches and understanding the physiopathology of the ischemic brain injury, experimental stroke models were critical for preclinical research.

Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

Ethnopharmacological Relevance: Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now.

Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling pathway.

Aim: To study the effects of Claulansine F (Clau F), a carbazole alkaloid isolated from the stem of Clausena lansium (Lour) Skeels, on neuritogenesis of PC12 cells, and to elucidate the mechanism of action.

Methods: Neuritogenesis of PC12 cells was quantified under an inverted microscope. Expression of the neurite outgrowth marker GAP-43 was detected using immunofluorescence.