The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.

The blood-brain barrier (BBB) is the most central component of the neurovascular unit (NVU) and is crucial for the maintenance of the internal environment of the central nervous system and the regulation of homeostasis. A multitude of neuroprotective agents have been developed to exert neuroprotective effects and improve the prognosis of patients with ischemic stroke. These agents have been designed to maintain integrity and promote BBB repair.

Flavonoids from as neuroprotective agents attenuate cerebral ischemia/reperfusion injury and via activating Nrf2.

Objectives: Cerebral ischemic stroke is a leading cause of death worldwide. Though timely reperfusion reduces the infarction size, it exacerbates neuronal apoptosis due to oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating the expression of antioxidant enzymes.

Effects of cilostazol on cognitive function and dementia risk: A systematic review and meta-analysis.

Background: Cilostazol is an antiplatelet drug and is used for stroke prevention and symptomatic peripheral vascular disease. Studies have reported the effects of cilostazol on cognitive function, but the results are inconsistent and have not been systematically assessed.

Methods: We systematically searched the PubMed, Embase, and Cochrane databases for relevant clinical studies.

The Therapeutic Effects of SP-8356, a Verbenone Derivative, with Multimodal Cytoprotective Mechanisms in an Ischemic Stroke Rat Model.

An ischemic cerebral stroke results from the interruption of blood flow to the brain, triggering rapid and complex cascades of excitotoxicity, oxidative stress, and inflammation. Current reperfusion therapies, including intravenous thrombolysis and mechanical thrombectomy, cause further brain injury due to reperfusion-induced cytotoxicity. To date, novel cytoprotective therapies that could address these challenges have yet to be developed, likely due to the limitations of targeting a single pathologic mechanism.

The Role of Endothelial L-PGDS in the Pro-Angiogenic and Anti-Inflammatory Effects of Low-Dose Alcohol Consumption.

Light alcohol consumption (LAC) may reduce the incidence and improve the prognosis of ischemic stroke. Recently, we found that LAC promotes cerebral angiogenesis and inhibits early inflammation following ischemic stroke. In addition, LAC upregulates lipocalin-type prostaglandin D2 synthase (L-PGDS) in the brain.

Edaravone's Safety Profile in Acute Ischemic Stroke.

Background: We aimed to evaluate the safety of intravenous edaravone for the treatment of acute ischemic stroke among Filipino patients. The study, categorized as Phase IV, spans from December 2022 to November 2023. The primary objective is to document side effects and serious adverse events during the 14-day edaravone infusion period.

ROS-responsive quercetin-based polydopamine nanoparticles for targeting ischemic stroke by attenuating oxidative stress and neuroinflammation.

Ischemic stroke (IS), a prevalent cerebrovascular disorder, is characterized by high morbidity rates and significant disability. However, relevant drug therapy for IS still suffers from limitations such as limited blood-brain barrier (BBB) penetration efficiency, single therapeutic target, short half-life, and strong side effects. The development of multi-target neuroprotective agents using natural drug molecules with low toxicity and combining them with nanotechnology to improve BBB permeability and drug utilization is an important direction in the development of IS therapeutic strategies.

Preferential Synaptic Type of GABA-A Receptor Ligands Enhancing Neuronal Survival and Facilitating Functional Recovery After Ischemic Stroke.

Selective enhancement of synaptic GABA signaling mediated by GABA-A receptors has been previously reported to promote functional recovery after ischemic stroke, while tonic GABA signaling has been detrimental. To identify agents that enhance synaptic signaling, we synthesized GABA-A ligands based on three chemotypes with affinity values p= 6.44-8.

CaMKIIα hub ligands are unable to reverse known phenotypes in Angelman syndrome mice.

Angelman Syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of ubiquitin-protein ligase E3A (UBE3A), resulting in marked changes in synaptic plasticity. In AS mice, a dysregulation of Ca/calmodulin-dependent protein kinase II alpha (CaMKIIα) was previously described. This has been convincingly validated through genetic rescue of prominent phenotypes in mouse cross-breeding experiments.

Magnesium sulfate in the management of acute ischemic stroke: A review of the literature and future directions.

Background: The management of acute ischemic stroke (AIS) was revolutionized within the last 15 years with the introduction of mechanical thrombectomy (MT) to standard of care. Despite the success of mechanical thrombectomy (MT) in achieving high recanalization rates for large vessel occlusion, functional independence post-treatment remains suboptimal. The current limitations of MT prompt evaluation of the role of adjunctive pharmacologic neuroprotective therapies to prevent excitotoxicity, cellular apoptosis, and inflammation that cause irreversible neuronal damage during AIS.

A fluorogenic ROS-triggered hydrogen sulfide donor for alleviating cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion injury is a severe neurovascular disease that urgently requires effective therapeutic interventions. Recently, hydrogen sulfide (HS) has garnered significant attention as a potential treatment for stroke; however, the precise and targeted delivery of HS remains a considerable challenge for its clinical application. We have developed HSDF-NH, a novel HS donor characterized by high selectivity, self-reporting capabilities, and the ability to penetrate the blood-brain barrier (BBB).

S100A4 exerts neuroprotective effects by attenuating blood-brain barrier disruption and oxidative stress via the PI3K/Akt/Nrf2 axis in ischemic stroke.

Ischemic stroke is a major cause of disability and mortality worldwide, with oxidative stress and blood-brain barrier (BBB) injury playing crucial roles in its pathogenesis. Our RNA sequencing results revealed that S100 calcium-binding protein A4 (S100A4) is highly expressed in the middle cerebral artery occlusion (MCAO) mouse model. We analyzed S100A4 expression in ischemic stroke patients and in mice subjected to the MCAO model.

Triolein alleviates ischemic stroke brain injury by regulating autophagy and inflammation through the AKT/mTOR signaling pathway.

Background: Triolein, a symmetric triglyceride exhibiting anti-inflammatory and antioxidant properties, has demonstrated potential in mitigating cellular damage. However, its therapeutic efficacy in ischemic stroke (IS) and underlying molecular mechanisms remain elusive. Given the critical roles of inflammation and autophagy in IS pathogenesis, this study aimed to elucidate the effects of triolein in IS and investigate its mechanism of action.

Synergistic effects of neuroprotective drugs with intravenous recombinant tissue plasminogen activator in acute ischemic stroke: A Bayesian network meta-analysis.

Neuroprotective drugs as adjunctive therapy for adults with acute ischemic stroke (AIS) remains contentious. This study summarizes the latest evidence regarding the benefits of neuroprotective agents combined with intravenous recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis. This study conducted a structured search of PubMed, the Cochrane Library, EMBASE, Wanfang Data, and CNKI databases from their inception to March 2024.

The therapeutic effects of salvianolic acids on ischemic stroke: From molecular mechanisms to clinical applications.

Ischemic stroke (IS), primarily caused by cerebrovascular occlusion, poses a significant public health challenge with limited effective therapeutic options. Evidence suggests that salvianolic acids (SAs), mainly from Salvia miltiorrhiza Bunge, have been formulated into injections and are widely used in clinical treatments for cardiovascular and cerebrovascular diseases, including stroke. The pharmacological properties of SAs include reducing neuroinflammation, alleviating oxidative stress injury, inhibiting cellular apoptosis, preserving endothelial function, maintaining blood-brain barrier integrity, and promoting angiogenesis.

N-butylphthalide (NBP) ameliorated ischemia/reperfusion-induced skeletal muscle injury in male mice via activating Sirt1/Nrf2 signaling pathway.

N-butylphthalide (NBP) has been reported to have potential protective effects in ischemic stroke via its antioxidative properties. The present study was aimed to investigate the protective effects of NBP on ischemia/reperfusion (I/R)-induced skeletal muscle injury. Mouse model of I/R-induced skeletal muscle injury and hypoxia/reoxygenation (H/R)-induced C2C12 myotube injury model were constructed to test the protective effects of NBP both in vivo and in vitro.

Randomized Controlled Trial of Cilostazol Addition for In-Stent Restenosis After Carotid Artery Stenting.

Background: Restenosis after carotid artery stenting (CAS) is associated with the risk of developing ischemic stroke. We aimed to evaluate the inhibitory effect of cilostazol addition on in-stent restenosis (ISR) in patients treated with CAS.

Methods: In a randomized, open-label, blind-end point trial, patients with symptomatic and asymptomatic carotid artery stenosis and scheduled for CAS were randomly assigned to adding cilostazol (50 or 100 mg, twice per day) on other antiplatelets from 3 days before CAS or not adding cilostazol.

Ethanol extracts of Cinnamomum migao H.W. Li attenuates neuroinflammation in cerebral ischemia-reperfusion injury via regulating TLR4-PI3K-Akt-NF-κB pathways.

Ethnopharmacological Relevance: Cinnamomum migao H.W. Li, commonly known as migao (MG), is used in the Miao region of China for treating cardiovascular and cerebrovascular diseases, attributed to its detoxifying (Jiedu in Chinese), activating blood circulation (Huoxue in Chinese), and promoting Qi circulation (Tongqi in Chinese) properties.

Polydopamine(PDA)-coated diselenide-bridged mesoporous silica-based nanoplatform for neuroprotection by reducing oxidative stress and targeting neuroinflammation in intracerebral hemorrhage.

Oxidative stress (OS) and neuroinflammation are critical pathological processes in secondary brain injury (SBI) after intracerebral hemorrhage(ICH), and their intimate interactions initiate and aggravate brain damage. Thus, targeting oxidative stress and neuroinflammation could be a promising therapeutic strategy for ICH treatment. Here, we report a high-performance platform using polydopamine (PDA)-coated diselenide bridged mesoporous silica nanoparticle (PDA-DSeMSN) as a smart ROS scavenger and ROS-responsive drug delivery system.