Ferroptosis and endoplasmic reticulum stress in ischemic stroke

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron metabolism.The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum stress.Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival.Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke.However,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke.This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

Next-generation regenerative therapy for ischemic stroke using peripheral blood mononuclear cells

Stroke is the second leading cause of death and the third leading cause of disability worldwide after heart disease.Researchers predict that stroke deaths and permanent disabilities will increase worldwide by the year 2050.Single-target therapies may be insufficient,because ischemic cerebral injury involves several mechanisms.Cell-mediated therapies are ideal,because they target multiple cell types to enhance protection and recovery.

Contribution of Stress Testing to the Management of Ischemic Heart Disease in Mali

Introduction: Exercise stress testing (on a treadmill or ergometer bicycle) is an important test in cardiology for diagnosing myocardial ischemia. This test in Mali is still in its beginning compared to other countries in the sub-region. The lack of data in Mali prompted this study, which aimed to evaluate the indications of this activity and its diagnostic contribution to cardiology in Mali. Materials and Methods: This was a retrospective, descriptive study. The study was conducted at the “TOUCAM” medical clinic in Kati based on the analysis of stress test reports between January 2016 and August 2022. Result: During the study period, we documented 73 patients who underwent exercise testing on a bicycle ergometer for suspected coronary heart disease. The mean age of our patients was 47.5 ± 13.8 years (14 and 79 years). Males accounted for the majority (78.1%). The sex ratio is 3.5. More than half of our patients were overweight or obese (77.1%). Hypertension and diabetes affected 52.1% and 25.8% of patients, respectively. 20.8% of patients had coronary artery disease. renin-angiotensin-aldosterone system blockers (56.8%) and beta-blockers (51.3%). The main indications were chest pain (63.0%) and ischemia detection (15.1%). A modified STEEP protocol was used. The majority of our patients (71.2%) achieved at least 85% of their maximum theoretical heart rate. The main reason for the termination of the study was fatigue (57.3%). The average duration was 11.3 ± 4.2 minutes. 24.7% thought the stress tests were positive and 17.8% thought they were controversial. Conclusion: This study demonstrates the importance of stress testing in the diagnosis and treatment of ischemic heart disease, especially in settings where we have very limited access to coronary angiography.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

Early antiplatelet therapy used for acute ischemic stroke and intracranial hemorrhage

In this editorial we comment on the article published by Zhang et al in the recent issue of World Journal of Clinical Cases.We evaluate their claims on the benefit of use of Aspirin in the early management of patients with ischemic stroke.We also comment on their contention of using aspirin in the early management of patients with intracranial hemorrhage,a practice not seen in modern medicine.Large clinical trials such as the International Stroke Trial and the Chinese Acute Stroke Trial have shown the benefit of Aspirin use within 48 h of patients with Acute Ischemic Stroke.The findings were corroborated in the open-label trial performed by Zhang et al in a smaller sample group of 25 patients where they showed improvement in functional scores at 90 days without an increase in adverse events.As such,this intervention is also recommended by the American Heart Association stroke guidelines from 2021.With regard to Intracranial hemorrhage,traditional practice has been to discontinue or avoid antiplatelet therapy in these patient groups.However,no studies have been done to evaluate this management strategy that is more borne out of the mechanism behind Aspirin’s effect on the coagulation pathway.Zhang et al evaluate the benefits of Aspirin on patients with low-volume intracranial hemorrhage,i.e.,less than 30 mL on computed tomo-graphy imaging,and show no increase in mortality.The caveat of this finding is that all outcomes were pooled into one group for results,and the number of patients was low.While more studies with larger patient groups are required,the data from Zhang et al suggests that patients with small-volume intracranial hemorrhages may benefit from Aspirin administration in the acute phase of management.

Congestive ischemic colitis successfully treated with antiinflammatory therapy: A case report

BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown pathophysiology.Excluding conservative management,such as fasting,no established treatment exists;therefore,surgical intervention should be considered in some cases if symptoms worsen.Current literature suggests that anti-inflam-matory agents may effectively treat congestive ischemic colitis.CASE SUMMARY We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ago.Postoperatively,follow-up included an annual colonoscopy and abdominal computed tomography(CT)at a local clinic.However,progressive erythema and edema of the sigmoid colon were observed 1 year postoperatively.Upon admission to our hospital,she complained of abdominal pain and diarrhea.Abdominal CT showed thickening of the sigmoid colon walls,and colonoscopy revealed erythema,edema,and multiple ulcers with exudate in the sigmoid colon.CT angiography showed engorgement of the sigmoid vasa recta without any vascular abnormalities.The diagnosis was congestive ischemic colitis,and we treated the patient with anti-inflammatory agents.After 2 mo of glucocorticoid therapy(20 mg once daily)and 7 mo of 5-aminosalicylate therapy(1 g twice daily),the ulcers completely healed.She has not experienced any recurrence for 2 years.CONCLUSION Anti-inflammatory therapy,specifically glucocorticoids and 5-aminosalicylate,has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project

BACKGROUND:Ischemic stroke refers to a disorder in the blood supply to a local area of brain tissue for various reasons and is characterized by high morbidity,mortality,and disability.Early reperfusion of brain tissue at risk of injury is crucial for the treatment of acute ischemic stroke.The purpose of this study was to evaluate comfort levels in managing acute stroke patients with hypoxemia who required endotracheal intubation after multidisciplinary in situ simulation training and to shorten the door-to-image time.METHODS:This quality improvement project utilized a comprehensive multidisciplinary in situ simulation exercise.A total of 53 participants completed the two-day in situ simulation training.The main outcome was the self-reported comfort levels of participants in managing acute stroke patients with hypoxemia requiring endotracheal intubation before and after simulation training.A 5-point Likert scale was used to measure participant comfort.A paired-sample t-test was used to compare the mean self-reported comfort scores of participants,as well as the endotracheal intubation time and door-to-image time on the fi rst and second days of in situ simulation training.The door-to-image time before and after the training was also recorded.RESULTS:The findings indicated that in situ simulation training could enhance participant comfort when managing acute stroke patients with hypoxemia who required endotracheal intubation and shorten door-to-image time.For the emergency management of hypoxemia or tracheal intubation,the mean post-training self-reported comfort score was signifi cantly higher than the mean pre-training comfort score(hypoxemia:4.53±0.64 vs.3.62±0.69,t=-11.046,P<0.001;tracheal intubation:3.98±0.72 vs.3.43±0.72,t=-6.940,P<0.001).We also observed a decrease in the tracheal intubation and door-to-image time and a decreasing trend in the door-to-image time,which continued after the training.CONCLUSION:Our study demonstrates that the implementation of in situ simulation training in a clinical environment with a multidisciplinary approach may improve the ability and confi dence of stroke team members,optimize the fi rst-aid process,and eff ectively shorten the door-to-image time of stroke patients with emergency complications.

Ischemic colitis induced by a platelet-raising capsule: A case report

BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia.Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur.IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of IC.CASE SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was given.The patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were stopped.Under the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the PLT.After treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the hospital.CONCLUSION PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia[1].Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur[2,3].The pathogenesis of this disease has not been extensively studied,but increased clotting ability has been recognized as an important factor in the pathogenesis of IC[4].People older than 60 years(especially women)who suffer from certain underlying diseases,such as cardiovascular and cerebrovascular diseases,diabetes,and shock,are the most prone to colon IC.The lesions can involve any segment of the colon,among which the left half of the colon,such as the sigmoid colon,descending colon and spleen region,is the most common site of lesions.This is because the region south of the sigmoid colon is the"watershed region"of the colonic blood supply,where vascular dysplasia may easily cause ischemia.In addition,the left half of the colon is supplied by the inferior mesenteric artery,which is at an acute angle to the abdominal aorta and affects blood perfusion.The rectum is supplied by both the inferior mesenteric artery and the rectal artery,and ischemia is rare.Therefore,the IC lesions were mainly in the left colon,and most of them were of the first pass type.The disease is relatively mild and can be cured after conservative medical treatment,so the prognosis is favorable[5-7].Once ischemia improves,the patient’s condition can recover in a relatively short time,and this condition can be distin-guished from other types of enteritis[5-7],such as infectious colitis,inflammatory bowel disease,pseudomembranous enteritis,diverticulitis,colon cancer,and acute mesenteric ischemia.Clinically,ischemic colitis can be divided into gangrene and nongrene.The latter can also be subdivided into transient and chronic types.Treatment for IC usually includes fasting,gastrointestinal decompression,intravenous nutritional support,improved circulation,fluid resuscitation,empirical use of antibiotics and other symptomatic supportive treatments,and attention should be given to the treatment of the primary disease.Most patients will experience improvements in clinical symp-toms within 1 to 2 d,and patients with complications may require surgery.However,IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of ischemic colitis.

Recurrent Transient Ischemic Attacks Revealing Cerebral Amyloid Angiopathy: A Comprehensive Case

This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.

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.

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

Cell polarization in ischemic stroke: molecular mechanisms and advances

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.