Effective Treatment For Ischemic Stroke Research Articles

The Role of Thrombo-inflammation in Ischemic Stroke: Focus on the Manipulation and Clinical Application.

Stroke leaves a great economic burden due to its high morbidity and mortality. Rapid revascularization of targeted vessel(s) is the effective treatment for ischemic stroke, but subsequent ischemia-reperfusion (I/R) injury is a common complication following revascularization, leading to microcirculation dysfunction and infarct volume increase. Thrombo-inflammation, the interaction between thrombosis and inflammation, plays a critical role in the pathophysiology of ischemic stroke. In the context of I/R injury, thrombo-inflammation consists of platelet activation, endothelial injury, and inflammatory cell infiltration. Numerous studies are devoted to exploring methods of regulating thrombo-inflammation to mitigate I/R injury post-stroke, including blocking activations of platelets and neutrophils. Drugs such as antiplatelet medications, anticoagulants, and glucocorticoids have been confirmed to have the potential to regulate thrombo-inflammation. Furthermore, several recently developed drugs have also shown promises in relieving I/R injury by manipulating thrombo-inflammation. However, the majority of these studies are still in the preclinical stage. Herein, in this review, we will address the mechanisms of thrombo-inflammation in ischemic stroke, related research advances, and particularly the clinical feasibility of thrombo-inflammation as a therapeutic strategy against I/R injury.

Endovascular Treatment of Acute Ischemic Stroke After Cardiac Interventions in the United States

Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis. To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States. This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023. Cardiac intervention during admission. The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled. Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29). In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.

Acupuncture for ischemic stroke: Where are we now?

Acupuncture is an effective treatment for ischemic stroke (IS) and plays a key role in neurological rehabilitation after IS. Acupuncture can improve the clinical symptoms of various complications after IS, including motor dysfunction, swallowing disorders, speech disorders, cognitive impairment, depression, insomnia, and fatigue. However, the mechanisms underlying the effects of acupuncture in IS remain unclear. Available evidence suggests that acupuncture may exert neuroprotective effects through neuroplasticity (neurogenesis and synaptogenesis), angiogenesis, cell proliferation and apoptosis, and regulation of oxidative stress, inflammation, and immunity. Further studies should be conducted to improve the high-quality evidence-based system of acupuncture intervention for IS, by focusing on the clinical and basic research design, increasing the sample size, standardizing and quantifying the standards of acupuncture operations, using multidisciplinary techniques and methods to systematically explore the key targets of acupuncture intervention for IS, and reveal the efficacy and mechanism of acupuncture in the treatment of IS.

Cases of successful thrombus extraction in ischemic stroke associated with the new coronavirus infection COVID-19

The issues of effective treatment of ischemic stroke (IS) are relevant, since it leads to a high percentage of disability and mortality throughout the world. The article presents 4 cases of patients with various pathogenetic variants of IS that developed against the background of a new coronavirus infection COVID-19 (degree of lung damage: CT-0 and CT1). Due to the presence of symptomatic occlusion of a large artery, these patients successfully underwent cerebral angiography followed by mechanical thrombus extraction (MTE), after which a significant improvement in neurological symptoms was observed. Results of the pathohistochemical examination of intraoperative material are presented. Patients were followed-up for 3 months. Despite the successful outcome of MTE in these cases, the impact of COVID-19 on the long-term prognosis of stroke patients after MTE remains to be determined. The results of treatment of patients with IS and COVID-19 who underwent MTE should be presented in larger and preferably prospective and multicenter studies.

PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons

Ischemic stroke is a neurological disorder caused by vascular stenosis or occlusion, accounting for approximately 87% of strokes. Clinically, the most effective therapy for ischemic stroke is vascular recanalization, which aims to rescue neurons undergoing ischemic insults. Although reperfusion therapy is the most effective treatment for ischemic stroke, it still has limited benefits for many patients, and ischemia-reperfusion (I/R) injury is a widely recognized cause of poor prognosis. Here, we aim to investigate the mechanism of protein phosphatase Mg2+/Mn2+ dependent 1 K (PPM1K) mediates metabolic disorder of branched-chain amino acids (BCAA) by promoting fatty acid oxidation led to ferroptosis after cerebral I/R injury. We established the I/R model in mice and used BT2, a highly specific BCAA dehydrogenase (BCKD) kinase inhibitor to promote BCAA metabolism. It was further verified by lentivirus knocking down PPM1K in neurons. We found that BCAA levels were elevated after I/R injury due to dysfunctional oxidative degradation caused by phosphorylated BCKD E1α subunit (BCKDHA). Additionally, the level of phosphorylated BCKDHA was determined by decreased PPM1K in neurons. We next demonstrated that BCAA could induce oxidative stress, lipid peroxidation, and ferroptosis in primary cultured cortical neurons in vitro. Our results further showed that BT2 could reduce neuronal ferroptosis by enhancing BCAA oxidation through inhibition of BCKDHA phosphorylation. We further found that defective BCAA catabolism could induce neuronal ferroptosis by PPM1K knockdown. Furthermore, BT2 was found to alleviate neurological behavior disorders after I/R injury in mice, and the effect was similar to ferroptosis inhibitor ferrostatin-1. Our findings reveal a novel role of BCAA in neuronal ferroptosis after cerebral ischemia and provide a new potential target for the treatment of ischemic stroke.

Exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling in ischemic stroke.

Umbilical cord-mesenchymal stem cells (UC-MSCs)-derived exosomes have been considered as an effective treatment for ischemic stroke. CircRNA BBS2 (circBBS2) was demonstrated to be down-regulated in patients with ischemic stroke. However, the role of UC-MSCs-derived exosomal circBBS2 in ischemic stroke and potential mechanisms remain unclear. Hypoxia/reperfusion (H/R)-exposed SH-SY5Y cells and middle cerebral artery occlusion (MCAO)-treated rats were served as in vitro and in vivo models of ischemic stroke. Target gene expression was detected by qRT-PCR. Cell viability was assessed by MTT assay. Ferroptosis was determined by iron, MDA, GSH, and lipid ROS levels. Protein levels were measured by Western blotting. The target relationships among circBBS2, miR-494, and SLC7A11 were validated by RNA-pull down, RIP, and dual-luciferase reporter assays. TTC and HE staining were performed to evaluate cerebral infarction volume and neuropathological changes. circBBS2 was lowly expressed and ferroptosis was triggered in MCAO rats and H/R-stimulated SH-SY5Y cells. UC-MSCs-derived exosomes enhanced cell viability and restrained ferroptosis via increasing circBBS2 expression in SH-SY5Y cells. Mechanistically, circBBS2 sponged miR-494 to enhance the SLC7A11 level. Knockdown of miR-494 or SLC7A11 reversedthe effects of silencing circBBS2 or miR-494 on ferroptosis of SH-SY5Y cells, respectively. Furthermore, UC-MSCs-derived exosomes attenuated ischemic stroke in rats via delivering circBBS2 to inhibit ferroptosis. UC-MSCs-derived exosomal circBBS2 enhanced SLC7A11 expression via sponging miR-494, therefore repressing ferroptosis and relieving ischemic stroke. Our findings shed light on a novel mechanism for UC-MSCs-derived exosomes in the treatment of ischemic stroke.

MicroRNA-204-5p Ameliorates Neurological Injury via the EphA4/PI3K/AKT Signaling Pathway in Ischemic Stroke.

Ischemic stroke has extremely high mortality and disability rates worldwide. miR-204-5p has been reported to be associated with neurological diseases. However, the relationship linking miR-204-5p to ischemic stroke and its molecular mechanism remain unclear. Herein, we found that expression of miR-204-5p was significantly decreased while EphA4 increased in vivo and vitro, which reached the peak at 24 h after cerebral ischemia/reperfusion. Then, we altered miR-204-5p expression in rats by cerebroventricular injection. Our study showed that miR-204-5p overexpression obviously reduced the brain infarction area and neurological score. We successfully cultured neurons to investigate the downstream mechanism. Upregulation of miR-204-5p increased cell viability and suppressed the release of LDH. Moreover, the proportion of apoptotic cells tested by TUNEL and flow cytometry and protein expression of Cleaved Caspase3 and Bax were inhibited. The relative expression of IL-6, TNF-α, and IL-1β was repressed. In contrary, knockdown of miR-204-5p showed the opposite results. Bioinformatics and a dual luciferase assay illustrated that EphA4 was a target gene. Further research studies demonstrated that the neuroprotective effects of miR-204-5p could be partially mitigated by upregulating EphA4. Next, we proved that the miR-204-5p/EphA4 axis furtherly activated the PI3K/AKT pathway. We thoroughly illustrated the role of neuroinflammation and apoptosis. However, whether there are other mechanisms associated with the EphA4/PI3K/AKT pathway needs further investigation. Altogether, the miR-204-5p axis ameliorates neurological injury via the EphA4/PI3K/AKT pathway, which is expected to serve as an effective treatment for ischemic stroke.

Gut-brain axis: Mechanisms and potential therapeutic strategies for ischemic stroke through immune functions.

After an ischemic stroke (IS) occurs, immune cells begin traveling to the brain and immune system from the gut and gastrointestinal tract, where most of them typically reside. Because the majority of the body's macrophages and more than 70% of the total immune cell pool are typically found within the gut and gastrointestinal tract, inflammation and immune responses in the brain and immune organs require the mobilization of a large number of immune cells. The bidirectional communication pathway between the brain and gut is often referred to as the gut-brain axis. IS usually leads to intestinal motility disorders, dysbiosis of intestinal microbiota, and a leaky gut, which are often associated with poor prognosis in patients with IS. In recent years, several studies have suggested that intestinal inflammation and immune responses play key roles in the development of IS, and thus may become potential therapeutic targets that can drive new therapeutic strategies. However, research on gut inflammation and immune responses after stroke remains in its infancy. A better understanding of gut inflammation and immune responses after stroke may be important for developing effective therapies. This review discusses the immune-related mechanisms of the gut-brain axis after IS and compiles potential therapeutic targets to provide new ideas and strategies for the future effective treatment of IS.

An Updated Review of Mitochondrial Transplantation as a Potential Therapeutic Strategy Against Cerebral Ischemia and Cerebral Ischemia/Reperfusion Injury.

Regardless of the progress made in the pathogenesis of ischemic stroke, it remains a leading cause of adult disability and death. To date, the most effective treatment for ischemic stroke is the timely recanalization of the occluded artery. However, the short time window and reperfusion injury have greatly limited its application and efficacy. Mitochondrial dysfunction and ATP depletion have become regarded as being hallmarks of neuropathophysiology following ischemic stroke. Mitochondrial transplantation is a novel potential therapeutic intervention for ischemic stroke that has sparked widespread concern during the past few years. This review summarizes and discusses the effects of mitochondrial transplantation in in vitro and in vivo ischemic stroke models. In addition, pharmacological interventions promoting mitochondrial transplantation are reviewed and discussed. We also discuss the potential challenges to the clinical application of mitochondrial transplantation in the treatment of ischemic stroke.

Targeting ASIC1a Promotes Neural Progenitor Cell Migration and Neurogenesis in Ischemic Stroke.

Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of proton-gated cation channels following ischemic stroke. However, the role of ASIC1a in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was expressed in NPCs with channel functionality, which could be activated by extracellular acidification. Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation, which could be primarily reversed by pharmacological or genetic disruption of ASIC1a. Invivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke. Subsequently, ASIC1a gain of function partially abrogated this effect. Moreover, the administration of ASIC1a antagonists (amiloride or Psalmotoxin 1) promoted functional recovery by enhancing NPC migration and neurogenesis. Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating NPC migration toward penumbra to repair lesions following ischemic stroke and even for other neurological diseases with the presence of niche acidosis.

Advancements in Hydrogel Application for Ischemic Stroke Therapy.

Ischemic stroke is a major cause of death and disability worldwide. There is almost no effective treatment for this disease. Therefore, developing effective treatment for ischemic stroke is urgently needed. Efficient delivery of therapeutic drugs to ischemic sites remained a great challenge for improved treatment of strokes. In recent years, hydrogel-based strategies have been widely investigated for new and improved therapies. They have the advantage of delivering therapeutics in a controlled manner to the poststroke sites, aiming to enhance the intrinsic repair and regeneration. In this review, we discuss the pathophysiology of stroke and the development of injectable hydrogels in the application of both stroke treatment and neural tissue engineering. We also discuss the prospect and the challenges of hydrogels in the treatment of ischemic strokes.

Preparation, In Vitro and In Vivo Evaluation of Nanoemulsion In Situ Gel for Transnasal Delivery of Traditional Chinese Medicine Volatile Oil from Ligusticum sinense Oliv.cv. Chaxiong

Ischemic stroke is a difficult-to-treat brain disease that may be attributed to a limited therapeutic time window and lack of effective clinical drugs. Nasal-brain administration is characterized by low systemic toxicity and is a direct and non-invasive brain targeting route. Preliminary studies have shown that the volatile oil of Chaxiong (VOC) has an obvious anti-ischemic stroke effect. In this work, we designed a nanoemulsion thermosensitive in situ gel (VOC-NE-ISG) loaded with volatile oil of Chaxiong for ischemia via intranasal delivery to rat brain treatment of cerebral ischemic stroke. The developed VOC-NE-ISG formulation has a suitable particle size of 21.02 ± 0.25 nm and a zeta potential of -20.4 ± 1.47 mV, with good gelling ability and prolonged release of the five components of VOC. The results of in vivo pharmacokinetic studies and brain targeting studies showed that intranasal administration of VOC-NE-ISG could significantly improve the bioavailability and had excellent brain-targeting efficacy of nasal-to-brain delivery. In addition, the results of pharmacodynamics experiments showed that both VOC-NE and VOC-NE-ISG could reduce the neurological deficit score of model rats, reducing the size of cerebral infarction, with a significant effect on improving ischemic stroke. Overall, VOC-NE-ISG may be a promising intranasal nanomedicine for the effective treatment of ischemic stroke.

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. Here, we comprehensively determined the spatiotemporal dynamic changes in brain lipids during the acute phase after reperfusion in a mouse model of transient middle cerebral artery occlusion, with or without rtPA administration, using desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI). Several phospholipids, sphingolipids, and neutral lipids were significantly altered both spatially and temporally at multiple timepoints after reperfusion, many of which were closely associated with expansion of the brain infarction territory and neurological function impairment. Furthermore, rtPA treatment significantly increased brain infarction, cerebral edema, and neurological deficits. Consistently, rtPA treatment caused extensive brain lipid alterations by facilitating brain-wide changes in lipid metabolism and inducing ischemic region-specific lipid changes. Overall, these results provide novel insights into how reperfusion therapy affects brain tissue and the outcome of stroke patients, and thus may facilitate the optimization of the treatment of ischemic stroke.

Immune response treated with bone marrow mesenchymal stromal cells after stroke

Stroke is a leading cause of death and long-term disability worldwide. Tissue plasminogen activator (tPA) is an effective treatment for ischemic stroke. However, only a small part of patients could benefit from it. Therefore, finding a new treatment is necessary. Bone marrow mesenchymal stromal cells (BMSCs) provide a novel strategy for stroke patients. Now, many patients take stem cells to treat stroke. However, the researches of the precise inflammatory mechanism of cell replacement treatment are still rare. In this review, we summarize the immune response of BMSCs treated to stroke and may provide a new perspective for stem cell therapy.

Efficacy and safety of butylphthalide in secondary prevention of stroke: study protocol for a multicenter, real world trial based on Internet

BackgroundAs one of the leading causes of morbidity and mortality, stroke and its recurrence has attracted more and more attention. Dl-3-n-butylphthalidle(NBP) has been widely used for treating acute ischemic stroke in China and shows a great clinical effect. NBP plays a role in different pathophysiological processes in the treatment of ischemic stroke, including antioxidants, anti-inflammatory, anti-apoptotic, anti-thrombosis, and mitochondrial protection. Many randomized, double-blind, placebo-controlled, multicenter clinical trials suggest that NBP is a safe and effective treatment for ischemic stroke. To sum up, the current research is mainly focused on the short-term treatment of stroke patients with RCT (randomized controlled trial). Therefore, we designed this study to confirm the role of butylphthalide in secondary stroke prevention in the real world.MethodsThis study will be a multicenter, prospective real-world trial. We would recruit 8000 patients with ischemic stroke from 78 public hospitals in China. All participants will be allocated to one of two parallel treatment groups according to their own wills: (1) butylphthalide group: 0.2 g of butylphthalide capsules three times daily plus routine treatment (aspirin 50-300 mg/d, clopidogrel 75 mg/d, etc.); (2) control group: routine treatment (aspirin 50-300 mg/d, clopidogrel 75 mg/d, etc.). Treatment duration is 90 consecutive days or more. The primary outcome is recurrence rate of stroke within 1 month, 3 months, 6 months and 1 year in butylphthalide group and control group. The secondary outcomes included NIHSS score, the mRS score, other clinical cardiovascular events within one year (sudden death / myocardial infarction / arrhythmia / heart failure, etc.), and adverse events of patients in groups. NIHSS will be captured in the first month after discharge, and the others will be captured at the same time points as the primary end point.DiscussionThis trial will be exploring the efficacy and safety of butylphthalide in secondary prevention of ischemic stroke to expand the scope of application of butylphthalide soft capsules and provide new ideas for enriching the secondary prevention of stroke.Trial registrationChinese Clinical Trial Registry (ChiCTR). Trial registration number: ChiCTR2000034481. Registered on 6 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=55800

Uncovering the Mechanism of the Xingnaojing Injection against Ischemic Stroke Using a Combined Network Pharmacology Approach and Gut Microbiota Analysis.

Objective To explore the brain protection mechanism of Xingnaojing injection (XNJ) against ischemic stroke (IS) by the network pharmacology approach and gut microbiota analysis. Methods We used network pharmacology analysis to identify the active components of XNJ and its potential targets against IS and inflammatory bowel disease (IBD) and carried out network analysis, functional annotation, and pathway enrichment analysis. Then, transient middle cerebral artery occlusion (tMCAO) mice model was used to verify the molecular mechanism of XNJ. Results 36 active compounds were identified from XNJ, and the effect of XNJ against IS was related to the VEGF signaling pathway, NF-kappa B signaling pathway, and gap junction. The effect of XNJ against IBD was related to the T cell receptor signaling pathway, NF-kappa B signaling pathway, and gap junction. In vitro experiments showed that XNJ significantly improved the neurological function of tMCAO mice, reduced the size of cerebral infarction, decreased the permeability of blood-brain barrier (BBB), downregulated the expressions of TLR4, MyD88, and NF-kappa B in the ischemic site, and upregulated the expressions of occludin and ZO-1 in the colon. High-throughput 16S rDNA gene sequencing showed that XNJ upregulated the levels of Akkermansia and downregulated the levels of Flavobacteriaceae, Deferribacteraceae, and Deferribacteres. XNJ increased the concentrations of the short-chain fatty acids (SCFAs) PA (propionate), VA (valerate), IBA (isobutyrate), and IVA (isovalerate) in the feces of the sham germ-free experiment group (SGFEG) mice. Conclusion IS causes dysbiosis of some specific bacteria in the gut microbiota. XNJ is an effective treatment for IS, and its mechanism was related to improving intestinal barrier function and regulating intestinal flora and SCFAs. Network pharmacology revealed that XNJ acts through multiple targets and multiple pathways.

Engineered biomimetic drug-delivery systems for ischemic stroke therapy

Ischemic stroke, the most common form of cerebrovascular disease, is a leading cause of death and disability throughout the world. Ischemic injury initiates cascade of pathological events comprising energy dwindling, calcium over accumulation, excitotoxicity, increased oxidative stress, mitochondrial dysfunction, inflammation and eventually cell death. Although in recent years, biomimetic drug-delivery systems (BDDS) hold exciting potential in modulating ischemic stroke, because of their special properties, including low toxicity and immunogenicity, biodegradability, ability to encapsulate endogenous biologically active molecules and cross the blood–brain barrier (BBB). However, the poor ability in targeting, homing, and/or combination applications of BDDS greatly reduces the therapeutic effect. Using engineering technology, BDDS can obtain active targeting ability to accumulate in specific cell types and tissues or increasing expression of therapeutic factors for enhancing therapeutic efficiency. In this review, we outline the recent progress in exploiting engineered BDDS for ischemic stroke and presented their fabrication processes, unique properties and enhancing treatment efficiency. On this base, the potentials and challenges of engineered BDDS in the treatment of ischemic stroke are revealed, and new thoughts and perspectives are proposed for the design of feasible engineered BDDS for effective treatment of ischemic stroke and other brain diseases.

Mitochondrial Quality and Quantity Control: Mitophagy Is a Potential Therapeutic Target for Ischemic Stroke.

Ischemic stroke is a cerebrovascular disease with high mortality and disability, which seriously affects the health and lives of people around the world. Effective treatment for ischemic stroke has been limited by its complex pathological mechanisms. Increasing evidence has indicated that mitochondrial dysfunction plays an essential role in the occurrence, development, and pathological processes of ischemic stroke. Therefore, strict control of the quality and quantity of mitochondria via mitochondrial fission and fusion as well as mitophagy is beneficial to the survival and normal function maintenance of neurons. Under certain circumstances, excessive mitophagy also could induce cell death. This review discusses the dynamic changes and double-edged roles of mitochondria and related signaling pathways of mitophagy in the pathophysiology of ischemic stroke. Furthermore, we focus on the possibility of modulating mitophagy as a potential therapy for the prevention and prognosis of ischemic stroke. Notably, we reviewed recent advances in the studies of natural compounds, which could modulate mitophagy and exhibit neuroprotective effects, and discussed their potential application in the treatment of ischemic stroke.

Neuroinflammatory Triangle Presenting Novel Pharmacological Targets for Ischemic Brain Injury.

Ischemic stroke is one of the leading causes of morbidity and mortality globally. Hundreds of clinical trials have proven ineffective in bringing forth a definitive and effective treatment for ischemic stroke, except a myopic class of thrombolytic drugs. That, too, has little to do with treating long-term post-stroke disabilities. These studies proposed diverse options to treat stroke, ranging from neurotropic interpolation to venting antioxidant activity, from blocking specific receptors to obstructing functional capacity of ion channels, and more recently the utilization of neuroprotective substances. However, state of the art knowledge suggests that more pragmatic focus in finding effective therapeutic remedy for stroke might be targeting intricate intracellular signaling pathways of the ‘neuroinflammatory triangle’: ROS burst, inflammatory cytokines, and BBB disruption. Experimental evidence reviewed here supports the notion that allowing neuroprotective mechanisms to advance, while limiting neuroinflammatory cascades, will help confine post-stroke damage and disabilities.

Hemodynamics of Leptomeningeal Collaterals after Large Vessel Occlusion and Blood Pressure Management with Endovascular Treatment.

Endovascular therapy (EVT) is an effective treatment for ischemic stroke due to large vessel occlusion (LVO). Unlike intravenous thrombolysis, EVT enables visualization of the restoration of blood flow, also known as successful reperfusion in real time. However, until successful reperfusion is achieved, the survival of the ischemic brain is mainly dependent on blood flow from the leptomeningeal collaterals (LMC). It plays a critical role in maintaining tissue perfusion after LVO via pre-existing channels between the arborizing pial small arteries or arterioles overlying the cerebral hemispheres. In the ischemic territory where the physiologic cerebral autoregulation is impaired and the pial arteries are maximally dilated within their capacity, the direction and amount of LMC perfusion rely on the systemic perfusion, which can be estimated by measuring blood pressure (BP). After the EVT procedure, treatment focuses on mitigating the risk of hemorrhagic transformation, potentially via BP reduction. Thus, BP management may be a key component of acute care for patients with LVO stroke. However, the guidelines on BP management during and after EVT are limited, mostly due to the scarcity of high-level evidence on this issue. In this review, we aim to summarize the anatomical and physiological characteristics of LMC to maintain cerebral perfusion after acute LVO, along with a landscape summary of the literature on BP management in endovascular treatment. The objective of this review is to describe the mechanistic association between systemic BP and collateral perfusion after LVO and thus provide clinical and research perspectives on this topic.