COVID-19 e a incidência de AVC isquêmico pós-infecção: uma revisão integrativa da literatura / COVID-19 and the incidence of post-infection ischemic stroke: an integrative literature review

O SARS-CoV-2 é um vírus que surgiu em 2019, sendo responsável por causar uma síndrome respiratória que foi denominada COVID-19. O vírus possui uma proteína, chamada proteína Spike, que interage com as ACE2, estando presente no trato respiratório e nas células endoteliais, causando inflamação, apoptose e efeitos pró-trombóticos que ativam a via de coagulação. Dessa maneira, presume-se que o estado de hipercoagulabilidade do vírus e a inflamação endotelial estejam relacionados à fisiopatologia do AVC isquêmico pós-infecção. O objetivo desta revisão foi analisar a fisiopatologia e a etiologia dos AVCs associados à infecção pelo vírus SARS-CoV-2 e seus fatores de risco. Foi realizada uma busca por trabalhos prévios nas plataformas PubMed e BVS, e um total de 26 artigos científicos foram incluídos após a aplicação de critérios de inclusão e exclusão. Através dos estudos analisados, observou-se a correlação do aumento da incidência do AVC pós-infecção pelo SARS-CoV-2, e os fatores de risco presentes principais foram hipertensão arterial, fibrilação atrial, diabetes mellitus, dislipidemia e insuficiência cardíaca. Em conclusão, a infecção por SARS-CoV-2 possui relação com o aumento da incidência de AVC, possivelmente por seu mecanismo trombótico e inflamatório dos endotélios.

SARS-CoV-2 is a virus that emerged in 2019, being responsible for causing a respiratory syndrome that was named COVID-19. The virus has a protein, called Spike protein, which interacts with ACE2, which are present in the respiratory tract and endothelial cells, causing inflammation, apoptosis and prothrombotic effects that activate the coagulation pathway. Thus, it is presumed that the hypercoagulable state of the virus and endothelial inflammation are related to the pathophysiology of postinfection ischemic stroke. The aim of this review was to analyze the pathophysiology and etiology of strokes associated with SARSCoV-2 virus infection and their risk factors. A search for previous works was carried out on PubMed and VHL platforms, and a total of 26 scientific articles were included after applying inclusion and exclusion criteria. Through the studies analyzed, a correlation was observed between the increased incidence of stroke after infection with SARS-CoV-2, and the main risk factors present were arterial hypertension, atrial fibrillation, diabetes mellitus, dyslipidemia and heart failure. In conclusion, SARS-CoV-2 infection is related to the increased incidence of stroke, possibly due to its thrombotic and endothelial inflammatory mechanism.

Proteína-C reactiva de alta sensibilidad y homocisteína en pacientes con enfermedad cerebrovascular isquémica

Fundamento: la proteína C reactiva de alta sensibilidad (PCR-as) y la homocisteína (Hci) parecen relacionarse con la enfermedad cerebrovascular isquémica, pero sus hallazgos sobre el riesgo y pronóstico de esta enfermedad resultan controversiales y no concluyentes. Objetivo caracterizar la proteína C reactiva de alta sensibilidad y homocisteína en pacientes con enfermedad cerebrovascular isquémica. Métodos: se realizó un estudio descriptivo y retrospectivo de corte transversal en pacientes con enfermedad cerebrovascular isquémica, ingresados en el Servicio de Ictus del Instituto de Neurología y Neurocirugía entre 2016 y 2019. Se recogieron variables demográficas, manifestaciones clínicas, tiempo de evolución, etiología y localización del infarto y factores riesgo. Se cuantificaron la PCR-as (riesgo cardiovascular) y la Hci. Resultados las medias de PCR-as (7,0±8,3 mg/L) y Hci (17,1±7,3 µM) fueron elevadas. El riesgo cardiovascular moderado y alto se presentaron en igual proporción (46,8 %). Hubo diferencias estadísticas en la relación entre el riesgo cardiovascular y la edad (p=0,00); pero ni el tiempo de evolución ni los factores de riesgo de la enfermedad mostraron este comportamiento. Los pacientes con riesgo cardiovascular alto (PCR-as >3 mg/L) y elevada Hci (>15 (M) exhibieron mayores frecuencias de etiologías aterotrombótica o cardioembólica. Conclusiones el riesgo cardiovascular aumenta en la medida que se incrementa la edad de pacientes con enfermedad cerebrovascular isquémica. Las características demográficas, clínicas y neurológicas no mostraron relación con el alto riesgo cardiovascular y los valores elevados de Hci, aunque se encontró una tendencia asociativa de la etiología aterotrombótica con el incremento de PCR-as y Hci.

Foundation: High-sensitivity C-reactive protein and homocysteine seem to be related to ischemic cerebrovascular disease, but their findings on the risk and prognosis of this disease are controversial and inconclusive. Objective: to characterize high sensitivity C-reactive protein and homocysteine in patients with ischemic cerebrovascular disease. Methods: a descriptive and retrospective cross-sectional study was carried out in patients with ischemic cerebrovascular disease, admitted to the Stroke Service of the Neurology and Neurosurgery Institute between 2016 and 2019. Demographic variables, clinical manifestations, time of evolution, etiology and infarction location, risk factors. High-sensitivity C-reactive protein (cardiovascular risk) and homocysteine were quantified. Results: the means of C-reactive protein (7.0±8.3 mg/L) and homocysteine (17.1±7.3 µM) were high. Moderate and high cardiovascular risk occurred in equal proportions (46.8%). There were statistical differences in the relationship between cardiovascular risk and age (p=0.00); but neither the time of evolution nor the risk factors of the disease showed this behavior. Patients with high cardiovascular risk (hs-CRP >3 mg/L) and high homocysteine (>15 (M), exhibited higher frequencies of atherothrombotic or cardioembolic etiologies. Conclusions: cardiovascular risk increases as the age of patients with ischemic cerebrovascular disease increases. Demographic, clinical and neurological characteristics did not show a relationship with high cardiovascular risk and high homocysteine values, although an associative trend of atherothrombotic etiology was found with increased high-sensitivity C-reactive protein and homocysteine.

Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践杂志

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Application of multidisciplinary in situ simulation training in the treatment of acute ischemic stroke: a quality improvement project / 世界急诊医学杂志（英文）

@#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 first 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 significantly 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 confidence of stroke team members, optimize the first-aid process, and effectively shorten the door-to-image time of stroke patients with emergency complications.

Effect of Salvianolic Acid B Combined with Puerarin on Pyroptosis of SH-SY5Y Cells Injured by Oxygen-glucose Deprivation/Reoxygenation / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of salvianolic acid B combined with puerarin in protecting the SH-SY5Y cells from the damage by oxygen-glucose deprivation/reoxygenation （OGD/R） based on pyroptosis. MethodSH-SY5Y cells were used to establish the model of OGD/R， and cells were classified into the control， OGD/R， 10 μmol·L-1 salvianolic acid B， 100 μmol·L-1 puerarin， 10 μmol·L-1 salvianolic acid B + 100 μmol·L-1 puerarin， and 10 μmol·L-1 NOD-like receptor protein 3 （NLRP3） inhibitor MCC950 groups. Except the control group， other groups were rapidly reoxygenated for 12 h after 6 h OGD for modeling. The cell survival rate was determined by the methyl thiazolyl tetrazolium （MTT） assay. An optical microscope was used to observe the cell morphology. A spectrophotometer was used to determine the content of lactic dehydrogenase （LDH） in culture supernatant. Cell damage was measured by Hoechst/PI staining. The mRNA levels of NLRP3， cysteinyl aspartate specific proteinase-1 （Caspase-1）， gasdermin D （GSDMD）， apoptosis-associated speck-like protein （ASC）， and interleukin-1β （IL-1β） were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The protein activation of Caspase-1 and NLRP3 was detected by immunofluorescence. Western blot was employed to determine the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1. ResultCompared with the control group， the OGD/R group showed decreased cell survival rate （P<0.01）， damaged cell morphology， increased leakage rate of LDH （P<0.01）， up-regulated mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.01）， and up-regulated protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.01）. Compared with the OGD/R group， salvianolic acid B， puerarin， and salvianolic acid B combined with puerarin improved cell survival rate （P<0.01）， and the combined treatment group outperformed salvianolic acid B and puerarin used alone （P<0.01）. Salvianolic acid B combined with puerarin and MCC950 both improved cell morphology， reduced the leakage of LDH （P<0.01）， alleviated cell damage， and down-regulated the mRNA levels of NLRP3， Caspase-1， GSDMD， ASC， and IL-1β （P<0.05， P<0.01） and also the protein levels of IL-1β， ASC， NLRP3， Caspase-1， and cleaved Caspase-1 （P<0.05， P<0.01）. ConclusionThe results indicated that salvianolic acid B combined with puerarin can alleviate the OGD/R-induced damage of SH-SY5Y cells by inhibiting pyroptosis.

Effect and Mechanism of N-acetylcysteine in Ischemic Stroke / 中山大学学报(医学科学版)

Ischemic stroke （CIS） refers to ischemic necrosis or softening of localized brain tissue caused by cerebral blood circulation disorders， ischemia and hypoxia. The incidence of CIS is the highest among cerebrovascular diseases. Reduced supply of oxygen and nutrients leads to severe loss of neurons and deficits in brain function in stroke patients. Developing treatments for ischemic stroke remains an important challenge in clinical medicine. The antioxidant N-acetylcysteine （NAC） is a precursor of glutathione， and evidence from animal models of ischemic stroke and some clinical studies suggest that NAC can effectively protect the brain from ischemic damage. In this paper， the mechanism of NAC in CIS is described from various aspects， such as anti-oxidation， inhibition of inflammation， protection of cerebral nerve and mitochondrial function， stabilization of arterial plaque and thrombolytic function， aiming to explore the relationship between NAC and CIS in depth from the basic level， and to provide a theoretical basis for the further application of NAC in the prevention and treatment of patients with ischemic stroke.

Recent progress of targeting Nrf2-ferroptosis to treat brain injury after ischemic stroke / 中国临床药理学与治疗学

Emerging evidences suggest that ferroptosis plays a vital role in the pathophysiological process of brain injury after Ischemic stroke. Accumulating evidence supports pharmacological inhibition of ferroptosis as a therapeutic target for brain injury after Ischemic stroke through activating nuclear factor erythroid 2-related factor 2 (Nrf2), which transcriptionally controls many key components of the ferroptosis pathway. In this review, briefly describe ferroptosis processes and the roles they play in contributing to brain injury after ischemic stroke in the brain. We then provide a critical overview of the relationship between Nrf2 signalling and ferroptosis. With a focus on discuss how therapeutic modulation of the Nrf2 pathway is a viable strategy to explore in the treatment of ferroptosis-driven brain injury after Ischemic stroke.

Staging Sequential Treatment of Ischemic Stroke Based on Syndrome Differentiation of Deficiency and Excess in Eight Principles / 中国实验方剂学杂志

The core of diagnosing and treating diseases in traditional Chinese medicine lies in syndrome differentiation. The eight principles of syndrome differentiation serve as guidance for syndrome differentiation. As one of the eight principles of syndrome differentiation， the differentiation of deficiency and excess is the basic and critical method. Ischemic stroke is currently the leading cause harming the health of Chinese residents. Although the hypotheses about the cause of ischemic stroke have evolved from external wind to the later internal wind and to the modern theory of toxin damaging the brain collaterals， they all believe that this disease is rooted in internal deficiency and external excess. According to available studies， although stroke is characterized by complex pathogenesis and rapid progression of syndromes， the key cause evolution has a regularity， that is， from excess to deficiency. This article analyzes the historical evolution of the etiology， pathogenesis， and syndrome differentiation schemes of stroke. There are diverse schemes for the syndrome differentiation of stroke， which make it difficult to choose in clinical practice. In view of this problem， this paper puts forward a new approach of staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess according to the evolution law of the key cause of stroke. Furthermore， we conducted a randomized controlled study on 100 patients with ischemic stroke to evaluate this new approach. The results showed that the staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess demonstrated definite clinical efficacy. In addition， this article reviews the previous research results of our team and the research achievements of other teams to preliminarily explore the relationship between stroke syndromes and biomarkers， aiming to provide an objective basis for unveiling the pathogenesis of stroke. In summary， according to the key cause evolution （from excess to deficiency）， the treatment of ischemic stroke by stages based on differentiation of deficiency and excess can facilitate the rapid intervention and improve the clinical efficacy on ischemic stroke.

Urinary Metabolomics Aanlysis of Differences in Effect of Aconiti Coreani Radix and Typhonii Rhizoma on Gerbils with Stroke / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Aconiti Coreani Radix and Typhonii Rhizoma on the urinary metabolites of gerbils with stroke by non-targeted metabolomics technique， and then to clarify the mechanism of the two， as well as their similarities and differences. MethodTwenty-four gerbils were randomly divided into control group（CG）， model group（MG）， Aconiti Coreani Radix group（RA） and Typhonii Rhizoma group（RT）. Except for the CG， ischemic stroke model was constructed using right unilateral ligation of gerbil carotid artery in the remaining groups. Except for the CG and MG， rats in the other groups received whole powder suspension（0.586 mg·g-1） was administered for 14 days. The neurological deficit in each group was scored by Longa scoring on days 0， 3， 7 and 14. After the end of administration， the serum， brain tissue and urine of gerbils in each group were collected， and the rate of cerebral infarction was detected by 2，3，5-triphenyltetrazolium chloride（TTC）， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， malondialdehyde（MDA）， superoxide dismutase（SOD）， glutathione（GSH）， and nitric oxide（NO） in serum and brain tissue were determined by enzyme-linked immunosorbent assay（ELISA）. The urine metabolomics of gerbils in each group was studied by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， and the data were processed by multivariate statistical analysis， and differential metabolites were screened based on value of variable importance in the projection（VIP） of the first principal component>1 and t-test P<0.05. Metabolic pathway analysis of the screened differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG） database and Metaboanalyst 5.0. ResultCompared with the CG， the neurological deficit score was significantly increased in the MG（P<0.05）， compared with the MG， the neurological deficit scores in the RA and RT were significantly reduced after 7 d and 14 d（P<0.05）. Compared with the CG， the rate of cerebral infarction was significantly increased in the MG（P<0.05）， compared with the MG， the rates of cerebral infarction in the RA and RT were significantly reduced（P<0.05）. Compared with the CG， the levels of IL-6， TNF-α， and MDA in the serum and brain tissue of gerbils from the MG were significantly increased（P<0.05）， and the levels of SOD， GSH and NO were significantly reduced（P<0.05）. Compared with the MG， Aconiti Coreani Radix and Typhonii Rhizoma could down-regulate the levels of IL-6， TNF-α and MDA， and up-regulated the levels of SOD， GSH and NO. A total of 112 endogenous differential metabolites were screened by urine metabolomics， of which 16 and 26 metabolites were called back by Aconiti Coreani Radix and Typhonii Rhizoma， and could be used as potential biomarkers for both treatments in stroke gerbils， respectively. The results of the pathway analysis showed that both Aconiti Coreani Radix and Typhonii Rhizoma had regulatory effects on arginine and proline metabolism， pyrimidine metabolism， and aminoacyl-tRNA biosynthesis. In addition， Aconiti Coreani Radix could also regulate riboflavin metabolism， Typhonii Rhizoma could also regulate purine metabolism， glycine， serine and threonine metabolism， arachidonic acid metabolism， biosynthesis of pantothenate and coenzyme A， and β-alanine metabolism. ConclusionBoth Aconiti Coreani Radix and Typhonii Rhizoma have better therapeutic effects on stroke， with Aconiti Coreani Radix having stronger effects. From the metabolomics results， the main metabolic pathways regulated by Aconiti Coreani Radix involve amino acid metabolism， oxidative stress and so on， while Typhonii Rhizoma mainly involve amino acid metabolism， lipid metabolism， energy metabolism， etc.

Study on Syndrome Research of Ischemic Stroke Combined with Obstructive Sleep Apnea-hypopnea Syndrome Based on Implicit Structure Method / 中国实验方剂学杂志

ObjectiveTo explore the common syndrome elements of cerebral ischemic stroke （CIS） complicated with obstructive sleep apnea-hypopnea syndrome （OSAHS）， reveal the characteristics of traditional Chinese medicine （TCM） syndromes of the disease， clarify the syndrome differentiation and syndrome types， provide evidence for clinical syndrome differentiation， and provide reference for establishing the TCM syndrome type standards of CIS complicated with OSAHS. MethodThe clinical information form of CIS complicated with OSAHS formulated by the research group was used for syndrome survey， and the four-examination information of 300 patients with CIS complicated with OSAHS was collected. The four-examination information of patients was analyzed by latent structure method and comprehensive cluster analysis， and the common syndrome elements of CIS complicated with OSAHS were extracted by combining the TCM basic theory and clinical experience. On this basis， the characteristics of TCM syndromes and the syndrome types in line with reality were summarized. ResultThe top five syndrome elements in patients with CIS and OSAHS are sleep snoring， open mouth breathing， physical obesity， night awakening and dizziness. The top five tongue and pulse manifestations are enlarged tongue， slippery pulse， slippery coating， thick and white coating and purple tongue. The disease locations are the lung， spleen， stomach， kidney， liver and brain. The nature of disease includes deficiency， depression， blood stasis， phlegm， dampness and fire. The clinical syndrome types include the syndrome of stagnation of phlegm and dampness， syndrome of phlegm-dampness blocking the mind， syndrome of spleen deficiency with dampness， syndrome of Yin deficiency leading to fire hyperactivity， syndrome of Qi depression blocking collaterals， syndrome of liver depression and blood stasis， syndrome of Qi deficiency with dampness， and syndrome of Yang deficiency induced water retention. ConclusionIn addition to the common phlegm-， dampness- and blood stasis-related syndromes in patients with CIS and OSAHS， there are also depression- and deficiency-related syndromes. The main etiology and pathogenesis is the disturbance of Qi movement. In clinical practice， attention should be paid to the specific situation of individual patients to differentiate between deficiency and excess， and the treatment should be performed by the method of soothing and reinforcing， or unblocking and clearing， or both.

Rehmanniae Radix Praeparata Improves Neurological Function of Ischemic Stroke Rats by Inhibiting Autophagy and Ferroptosis / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg-1 and 7 g·kg-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Aproximación al diagnóstico infarto cerebral isquémico en adultos jóvenes / Approach to the diagnosis of ischemic cerebral infarction in Young adults / Approach to the diagnosis of ischemic cerebral infarction in Young adults / Abordagem para o diagnóstico de infarto cerebral isquêmico em adultos jovens

Introducción: El infarto cerebral isquémico (ICI) en adultos jóvenes ha emergido como un relevante problema de salud debido al incremento de su incidencia, alta mortalidad, larga duración del tiempo de la discapacidad y consecuencias sociales. Objetivo: Describir una aproximación al diagnóstico del infarto cerebral isquémico en adultos jóvenes sobre la base de la clasificación etiopatogénica, historia e investigaciones complementarias. Método: Se realizó una extensa revisión bibliográfica con el buscador Google Académico, en las bases de datos bibliográficas PubMed, SciELO y Medline, y con la búsqueda de palabras claves; siendo escogidos 32 artículos cuyo título y resumen se relacionaron con el tema de la presente revisión. Desarrollo: Los subtipos etiopatogénicos del infarto cerebral isquémico en adultos jóvenes difieren al compararlo con adultos mayores, y sus causas etiológicas son más variadas y heterogéneas. Los factores de riesgo, antecedentes patológicos personales y familiares, manifestaciones clínicas no neurológicas y neurológicas, permiten un acercamiento al diagnóstico, mientras que las investigaciones complementarias facilitan la confirmación del diagnóstico, la localización y tamaño del infarto isquémico, el establecimiento de la causa etiológica y el sustento de las decisiones terapéuticas. Consideraciones finales: La historia y manifestaciones clínicas obtenidas mediante el interrogatorio y examen físico, unido a las investigaciones complementarias, posibilita la aproximación al diagnóstico del subtipo etiopatogénico y a la causa del infarto cerebral isquémico en adultos jóvenes, lo que mejora las posibilidades de tratamiento del mismo.(AU)

Introduction: Ischemic stroke in young adults has emerged as a relevant health problem today due to its increased incidence, high mortality, the duration of the disability and social consequences. Objective: To describe an approach in diagnosis of ischemic stroke in young adults based on etiopathogenic classification, history and complementary investigations. Method: A wide-ranging bibliographic review was carried out using Google Scholar, searching in bibliographic databases like PubMed, SciELO and Medline, and searching different keywords; 32 articles were chosen in the process with title and abstract were linked with the subject of this review. Development: The etiopathogenic subtypes of ischemic stroke in young adults differ with regard to older adults, and its etiologic causes are more diverse and heterogeneous. Risk factors, personal and family pathological history, non-neurological and neurological clinical manifestations, allow an approach to diagnosis, while complementary investigations facilitate the confirmation of diagnosis, the location and size of the ischemic infarction, definition of the etiological cause and the support of therapeutic decisions. Final considerations: The history and clinical manifestations obtained through interrogation and physical examination, in association with complementary investigations, made it possible an approach to diagnosis of etiopathogenic subtype and the cause of ischemic brain infarction in young adults improving treatment possibilities.(AU)

Introdução: O acidente vascular cerebral (AVC) isquêmico em adultos jovens emergiu como um problema de saúde relevante devido à sua crescente incidência, elevada mortalidade, longa duração da incapacidade e consequências sociais. Objetivo: Descrever uma abordagem ao diagnóstico do AVC isquêmico em adultos jovens baseada na classificação etiopatogénica, na história e em exames complementares. Método: Foi realizado uma extensa revisão bibliográfica utilizando o motor de busca Google Scholar, as bases de dados bibliográficas PubMed, SciELO e Medline, e uma pesquisa por palavras-chave; foram selecionados 32 artigos cujo título e resumo estavam relacionados com o tema desta revisão. Desenvolvimento: Os subtipos etiopatogênicos do AVC isquêmico em adultos jovens diferem quando comparados aos adultos mais velhos, e suas causas etiológicas são mais variadas e heterogêneas. Os fatores de risco, os antecedentes patológicos pessoais e familiares, as manifestações clínicas não neurológicas e neurológicas permitem uma aproximação ao diagnóstico, enquanto as investigações complementares facilitam a confirmação do diagnóstico, a localização e o tamanho do infarto isquêmico, o estabelecimento da causa etiológica e o apoio às decisões terapêuticas. Considerações finais: A história e as manifestações clínicas obtidas por meio de questionamento e exame físico, juntamente com investigações complementares, permitem abordar o diagnóstico do subtipo etiopatogênico e a causa do AVC isquêmico em adultos jovens, melhorando as possibilidades de seu tratamento.(AU)

General anesthesia versus conscious sedation in mechanical thrombectomy for patients with acute ischemic stroke: systematic review and meta-analysis / Anestesia geral versus sedação consciente na trombectomia mecânica para pacientes com AVC isquêmico agudo: revisão sistemática e metanálise

Abstract Background After recently published randomized clinical trials, the choice of the best anesthetic procedure for mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is not definite. Objective To compare the efficacy and safety of general anesthesia (GA) versus conscious sedation (CS) in patients with AIS who underwent MT, explicitly focusing on procedural and clinical outcomes and the incidence of adverse events. Methods PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) comparing GA versus CS in patients who underwent MT due to LVO-AIS. Odds ratios (ORs) were calculated for binary outcomes, with 95% confidence intervals (CIs). Random effects models were used for all outcomes. Heterogeneity was assessed with I2 statistics. Results Eight RCTs (1,300 patients) were included, of whom 650 (50%) underwent GA. Recanalization success was significantly higher in the GA group (OR 1.68; 95% CI 1.26-2.24; p < 0.04) than in CS. No significant difference between groups were found for good functional recovery (OR 1.13; IC 95% 0.76-1.67; p = 0.56), incidence of pneumonia (OR 1.23; IC 95% 0.56- 2,69; p = 0.61), three-month mortality (OR 0.99; IC 95% 0.73-1.34; p = 0.95), or cerebral hemorrhage (OR 0.97; IC 95% 0.68-1.38; p = 0.88). Conclusion Despite the increase in recanalization success rates in the GA group, GA and CS show similar rates of good functional recovery, three-month mortality, incidence of pneumonia, and cerebral hemorrhage in patients undergoing MT.

Resumo Antecedentes A trombectomia mecânica (TM) é o padrão de tratamento para pacientes com acidente vascular cerebral isquêmico agudo (AVCI) devido à oclusão de grandes vasos (OGV). No entanto, ainda não está claro qual é o procedimento anestésico mais benéfico para a TM. Objetivo Nosso objetivo foi comparar a eficácia e a segurança da anestesia geral (AG) versus sedação consciente (SC) em pacientes com AVCI submetidos à TM, focando especificamente nos resultados procedimentais e clínicos, bem como na incidência de eventos adversos. Métodos Foram realizadas buscas sistemáticas nas bases PubMed, Embase e Cochrane por ensaios clínicos randomizados (ECRs) comparando AG versus SC em pacientes submetidos à TM devido a AVCI por OGV. Razões de chances (ORs) foram calculadas para desfechos binários, com intervalos de confiança de 95% (ICs). Modelos de efeitos aleatórios foram usados para todos os resultados. A heterogeneidade foi avaliada com estatísticas I2. Resultados Oito ensaios clínicos randomizados (1.300 pacientes) foram incluídos, dos quais 650 (50%) foram submetidos à AG. O sucesso da recanalização foi significativamente maior no grupo AG (OR 1,68; IC 95% 1,26-2,24; p < 0,04) em comparação com SC. No entanto, não houve diferença significativa entre os grupos para recuperação funcional adequada (OR 1,13; IC 95% 0,76-1,67; p = 0,56), incidência de pneumonia (OR 1,23; IC 95% 0,56- 2,69; p = 0,61), mortalidade em três meses (OR 0,99; IC 95% 0,73- 1,34; p = 0,95) ou hemorragia cerebral (OR 0,97; IC 95% 0,68- 1,38; p = 0,88). Conclusão Apesar do aumento significativo nas taxas de sucesso de recanalização no grupo AG, AG e SC mostram taxas semelhantes de recuperação funcional, mortalidade, pneumonia e hemorragia em pacientes com AVCI submetidos à TM.

Morbimortality and determinants of reperfusion in ischemic stroke

SUMMARY BACKGROUND: Cerebrovascular accident (or stroke) and ischemic heart disease are the the major causes of death in the world. It is estimated that about 85% of strokes are ischemic in origin. Reperfusion therapy in the acute phase of ischemic stroke with a recombinant human tissue plasminogen activator is effective, but some factors influence the success of this treatment. OBJECTIVE: The aim of this study was to evaluate clinical aspects and possible determinants for reperfusion after venous thrombolysis. METHODS: This is a retrospective, cross-sectional, observational study based on a review of hospital records of inpatients diagnosed with ischemic stroke treated with intravenous thrombolysis, the main outcome being reperfusion or not. RESULTS: Data from this study revealed a predominance of females in the group of reperfused patients and males in the non-reperfused group, both maintaining moderate severity on the National Institutes of Health Stroke Scale and admission without statistical significance (p>0.18). In addition, the mean admission severity score was 13.2 for the group of reperfused patients and 14.2 for those not reperfused, and the mean ejection fraction of both groups was within normal functionality, with a mean of 0.50 for reperfused patients and 0.62 for non-reperfused patients. CONCLUSION: We found an association between successful venous chemical thrombolysis reperfusion and lower mortality in patients with acute stroke.

Independência funcional, aspectos clínicos e fatores sociodemográficos em pacientes na fase aguda do Acidente Vascular Cerebral: uma análise de associação / Functional independence, clinical aspects, and sociodemographic factors in patients in the acute phase of stroke: an association analysis

RESUMO Objetivo Analisar a associação da independência funcional com aspectos clínicos de comprometimento neurológico, a localização e extensão do dano neuronal e os fatores sociodemográficos em pacientes na fase aguda do AVC. Método Estudo analítico de recorte transversal, realizado com 90 pacientes adultos e idosos acometidos por AVC isquêmico, que tiveram admissão no ambiente hospitalar nas primeiras 24 horas após o evento vascular. A coleta dos dados referentes aos aspectos clínicos e fatores sociodemográficos foi realizada pelo prontuário eletrônico e/ou entrevista para descrever o perfil dos pacientes, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale e a Medida de Independência Funcional. Resultados O comprometimento neurológico, de acordo com a National Institute of Health Stroke Scale, foi associado à funcionalidade nas primeiras 24 horas após o AVC. Além disso, a presença de hipertensão arterial, idade, trabalho inativo, tabagismo e extensão do dano neuronal estiveram associados à dependência funcional, mas não permaneceram no modelo final deste estudo. Conclusão A dependência funcional está associada à hipertensão arterial, idade, trabalho inativo, tabagismo, extensão do dano neuronal e grau de comprometimento neurológico nas primeiras 24 horas após o evento vascular. Além disso, um nível mais elevado de comprometimento neurológico foi independentemente associado a níveis aumentados de dependência funcional.

ABSTRACT Purpose To analyze the association of functional independence with clinical aspects of neurological impairment, the location and extent of neuronal damage and sociodemographic factors in patients in the acute phase of stroke. Methods Analytical cross-sectional study in 90 adult and older patients affected by ischemic stroke, admitted to the hospital within 24 hours of the vascular event. Sociodemographic factors and clinical aspects data were collected from electronic medical records and/or interviews in order to depict the patients'profile, Oxfordshire Community Stroke Project, Alberta Stroke Programme Early CT Score, National Institute of Health Stroke Scale, and Functional Independence Measure. Results Neurological impairment, according to the National Institute of Health Stroke Scale, was associated with functioning in the first 24 hours after the stroke. Furthermore, the presence of arterial hypertension, age, inactive work, smoking and extent of neuronal damage were associated with functional dependence, but did not remain in the final model of this study. Conclusion Functional dependence is associated with arterial hypertension, age, inactive work, smoking, extent of neuronal damage, and degree of neurological impairment in the first 24 hours after the vascular event. Furthermore, a higher level of neurological impairment was independently associated with increased levels of functional dependence.

Evaluación de parámetros inflamatorios, trombóticos y variantes genéticas en pacientes con ataque cerebrovascular isquémico que se asisten en un hospital de Uruguay

Introducción: El ataque cerebrovascular es la segunda causa de muerte en adultos en el mundo occidental y una de las principales causas de discapacidad permanente, aumentando su frecuencia con la edad, el 85 % es de tipo isquémico. Objetivos: Analizar parámetros trombofílicos, hipofibrinolíticos y genéticos en pacientes con ataque cerebrovascular isquémico y evaluar la posible asociación de estos con factores de riesgo cardiovascular. Metodología: Se utilizó un cuestionario para evaluar la presencia de factores de riesgo cardiovascular en 114 pacientes incluidos en el estudio con diagnóstico de ataque cerebrovascular isquémico. Proteína C y antitrombina fueron determinados mediante métodos cromogénicos, resistencia a la proteína C activada e inhibidor lúpico mediante métodos coagulométricos y proteína S libre, inhibidor del activador del plasminógeno-1, homocisteína y lipoproteína (a) por métodos inmunoquímicos. Fibrinógeno fue determinado por coagulometría y proteína C reactiva por inmunoturbidimetría, ambos contra un grupo control. Las variantes genéticas factor V Leiden, protrombina G20210A, rs1205 (gen PCR), rs1800779 (gen NOS3) y rs2257073 (gen ASB10) fueron analizadas mediante real-time PCR, comparando los últimos tres con una población de referencia. La alteración de las frecuencias de las variables fue determinada por análisis estadístico chi-cuadrado. Resultados: Tres de los cuatro pacientes jóvenes estudiados presentaron indicadores de trombofilia. El resto de los parámetros alterados fueron homocisteína 30.1% (22.4-39.1), lipoproteína (a) 32.1% (24.1-41.4), inhibidor del activador del plasminógeno-1 36.0% (27.8-45.1), fibrinógeno 12.3% (7.5-19.6) y proteína C reactiva 78.1% (69.6-84.7). Se encontró asociación (p < 0.05) entre ciertos factores de riesgo cardiovascular y los parámetros evaluados como hipertensión/proteína C reactiva, dislipemia/lipoproteína (a), arritmia/lipoproteína (a) y arritmia/fibrinógeno. Para pacientes con ataque cerebrovascular isquémico solo la variante rs1205 mostró una frecuencia más alta del alelo T. Conclusiones: Este estudio revela la importancia de analizar la trombofilia en pacientes jóvenes, especialmente en aquellos sin factores de riesgo cardiovascular, así como el rol de la hipofibrinolisis, inflamación y algunas variantes genéticas en el desarrollo de ataque cerebro vascular isquémico.

Introduction: Stroke is the second cause of death in adults in the Western world and one of the main causes of permanent disability, increasing in frequency with age; 85% are ischemic. Objectives: To analyze thrombophilic, hypofibrinolytic, inflammatory, and genetic parameters in patients with ischemic stroke and evaluate possible associations with vascular risk factors. Methodology: Questionnaires were used to evaluate vascular risk factors in 114 patients included in the study with ischemic stroke diagnosis. Protein C and Antithrombin were determined by chromogenic assays, Activated Protein C Resistance and Lupus Anticoagulant were determined with by coagulometry and Free Protein S, Plasminogen activator inhibitor-1, Homocysteine and Lipoprotein (a) by immunochemistry. Fibrinogen was assayed by coagulometry and C-reactive protein by immunoturbidimetry, both against a control group. Factor V Leiden, Prothrombin G20210A, rs1205 (CRP gene), rs1800779 (NOS3 gene) and rs2257073 (ASB10 gene) genetic variants were analyzed by Real-Time PCR, comparing the last three with a reference population. Alteration frequencies of the variables were determined by chi-square statistical analysis. Results: Three out of four of the young patients studied presented indicators of thrombophilia. The rest of the altered parameters were Homocysteine 30.1% (22.4-39.1), Lipoprotein (a) 32.1% (24.1-41.4), Plasminogen activator inhibitor-1 36.0% (27.8-45.1), Fibrinogen 12.3% (7.5-19.6) and C-reactive protein 78.1% (69.6-84.7). Associations were found (p<0.05) between certain vascular risk factors and parameters evaluated, namely hypertension/C-reactive protein, dyslipidemia/lipoprotein (a), arrhythmia/lipoprotein (a) and arrhythmia/fibrinogen. For ischemic stroke patients only the genetic variant rs1205 showed higher frequency of the T allele. Conclusions: This study reveals the importance of analyzing thrombophilia in young patients, especially those without vascular risk factors, as well as the role of hypofibrinolysis, inflammation and some genetic variants in the development of ischemic stroke.

Introdução: O AVC é a segunda causa de morte em adultos no mundo ocidental e uma das principais causas de incapacidade permanente, aumentando de frequência com a idade; 85% são isquémicos. Metas: Analisar os parâmetros trombofílicos, hipofibrinolíticos e genéticos em pacientes com acidente vascular cerebral isquêmico e avaliar a possível associação com fatores de risco cardiovascular. Metodologia: Um questionário foi utilizado para avaliar a presença de fatores de risco cardiovascular em 114 pacientes incluídos no estudo com diagnóstico de acidente vascular cerebral isquêmico. Proteína C e antitrombina foram determinadas por métodos cromogênicos, resistência à proteína C ativada e inibidor de lúpus por métodos coagulométricos e proteína S livre, inibidor do ativador do plasminogênio-1, homocisteína e lipoproteína (a) por métodos imunoquímicos. O fibrinogênio foi determinado por coagulometria e a proteína C-reativa por imunoturbidimetria, ambos contra um grupo controle. As variantes genéticas fator V Leiden, protrombina G20210A, rs1205 (gene PCR), rs1800779 (gene NOS3) e rs2257073 (gene ASB10) foram analisadas por PCR em tempo real, comparando as três últimas com uma população de referência. As frequências de alteração das variáveis ​​foram determinadas pela análise estatística qui-quadrado. Resultados: Três dos quatro pacientes jovens estudados apresentaram indicadores de trombofilia. O resto dos parâmetros alterados foram homocisteína 30,1% (22,4-39,1), lipoproteína (a) 32,1% (24,1-41,4), inibidor do ativador de plasminogênio-1 36,0% (27,8-45,1), fibrinogênio 12,3% (7,5-19,6) e proteína C reativa 78,1% (69,6-84,7). Foi encontrada associação (p<0,05) entre alguns fatores de risco cardiovascular e os parâmetros avaliados como hipertensão/proteína C reativa, dislipidemia/lipoproteína (a), arritmia/lipoproteína (a) e arritmia/fibrinogênio. Para pacientes com acidente vascular cerebral isquêmico apenas a variante rs1205 apresentou maior frequência do alelo T. Conclusões: Este estudo revela a importância de analisar a trombofilia em pacientes jovens, especialmente aqueles sem fatores de risco cardiovascular, bem como o papel da hipofibrinólise, inflamação e algumas variantes genéticas no desenvolvimento do acidente vascular cerebral isquêmico.

Reperfusion therapy for acute ischemic stroke: where are we in 2023? / Terapia de reperfusão para o acidente vascular isquêmico agudo: onde estamos em 2023?

Abstract Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Resumo Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Estatinas en la prevención primaria, secundaria y terciaria del ictus isquémico / Statins in the Primary, Secondary and Tertiary Prevention of Ischemic Stroke

Introducción: El ictus isquémico representa la tercera causa de mortalidad en el mundo y la primera causa de discapacidad. Objetivos: Describir los efectos beneficiosos de la prescripción de las estatinas en la prevención primaria, secundaria y terciaria del ictus isquémico. Métodos: Se realizó una revisión bibliográfica sobre la prescripción de estatinas en la prevención primaria, secundaria y terciaria del ictus isquémico. Se revisaron más de 400 artículos publicados en PubMed, Cochrane y Medline. Conclusiones: El empleo de estatinas disminuye la mortalidad en la prevención primaria y secundaria, se utiliza precozmente en la fase aguda (prevención terciaria), disminuye el área infartada, existe una mejoría clínica y disminuyen los reactantes de la fase aguda como la proteína C reactiva(AU)

Introduction: Ischemic stroke represents the third cause of mortality worldwide and the first cause of disability. Objective: To describe the beneficial effects of the prescription of statins in the primary, secondary and tertiary prevention of ischemic stroke. Methods: A bibliographic review on the prescription of statins in the primary, secondary and tertiary prevention of ischemic stroke was carried out. More than 400 articles published in MEDLINE/PubMed and Cochrane were reviewed. Only 50 articles met the selection criteria, which were published from May 2021 to June 2022. Conclusions: The use of statins decreases mortality in primary and secondary prevention. If they are used early in the acute phase (tertiary prevention), the infarcted area decreases, there is clinical improvement and acute phase reactants such as C-reactive protein decrease(AU)