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1.
Crit Care ; 28(1): 5, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167175

RESUMO

BACKGROUND: Acute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI. METHODS: Subjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks. RESULTS: Eighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006). CONCLUSIONS: Among patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days. TRIAL REGISTRATION: URL: www. CLINICALTRIALS: gov . Unique identifier: NCT03868007. Registered 8 March 2019.


Assuntos
AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Método Duplo-Cego , Resultado do Tratamento , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia
2.
Stroke ; 54(9): 2442-2445, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37497674

RESUMO

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.


Assuntos
Isquemia Encefálica , Pós-Condicionamento Isquêmico , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Cães , Traumatismo por Reperfusão/prevenção & controle , Hemorragias Intracranianas , Trombectomia/efeitos adversos , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/cirurgia , Resultado do Tratamento
3.
Neurobiol Dis ; 184: 106200, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37321419

RESUMO

Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system, are integral to axonal integrity and function. Hypoxia-ischemia episodes can cause severe damage to these vulnerable cells through excitotoxicity, oxidative stress, inflammation, and mitochondrial dysfunction, leading to axonal dystrophy, neuronal dysfunction, and neurological impairments. OLs damage can result in demyelination and myelination disorders, severely impacting axonal function, structure, metabolism, and survival. Adult-onset stroke, periventricular leukomalacia, and post-stroke cognitive impairment primarily target OLs, making them a critical therapeutic target. Therapeutic strategies targeting OLs, myelin, and their receptors should be given more emphasis to attenuate ischemia injury and establish functional recovery after stroke. This review summarizes recent advances on the function of OLs in ischemic injury, as well as the present and emerging principles that serve as the foundation for protective strategies against OLs deaths.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/metabolismo , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Sistema Nervoso Central/metabolismo
4.
J Med Genet ; 59(4): 351-357, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33811136

RESUMO

BACKGROUND: Progressive cavitating leukoencephalopathy (PCL) is thought to result from mutations in nuclear genes affecting mitochondrial function and energy metabolism. To date, mutations in two subunits of complex I, NDUFS1 and NDUFV1, have been reported to be related to PCL. METHODS: Patients underwent clinical examinations, brain MRI, skin biopsy and muscle biopsy. Whole-genome or whole-exome sequencing was performed on the index patients from two unrelated families with PCL. The effects of the mutations were examined through complementation of the NDUFV2 mutation by cDNA expression. RESULTS: The common clinical features of the patients in this study were recurring episodes of acute or subacute developmental regression that appeared in the first years of life, followed by gradual remissions and prolonged periods of stability. MRI showed leukoencephalopathy with multiple cavities. Three novel NDUFV2 missense mutations were identified in these families. Complex I deficiency was confirmed in affected individuals' fibroblasts and a muscle biopsy. Functional and structural analyses revealed that these mutations affect the structural stability and function of the NDUFV2 protein, indicating that defective NDUFV2 function is responsible for the phenotypes in these individuals. CONCLUSIONS: Here, we report the clinical presentations, neuroimaging and molecular and functional analyses of novel mutations in NDUFV2 in two sibling pairs of two Chinese families presenting with PCL. We hereby expand the knowledge on the clinical phenotypes associated with mutations in NDUFV2 and the genotypes causative for PCL.


Assuntos
Leucoencefalopatias , Doenças Mitocondriais , NADH Desidrogenase , Exoma , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Doenças Mitocondriais/genética , Mutação , NADH Desidrogenase/genética , Sequenciamento do Exoma
5.
BMC Ophthalmol ; 23(1): 455, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957614

RESUMO

PURPOSE: To evaluate the peripapillary retinal nerve fiber layer thickness (pRNFL) in patients with intracranial atherosclerotic stenosis (ICAS). METHODS: A cross-sectional study was performed in a general hospital. The intracranial atherosclerotic stenosis was evaluated by digital subtraction angiography (DSA), computed tomography angiography (CTA) or magnetic resonance angiography (MRA). High-definition optical coherence tomography (HD-OCT) was used to evaluate the peripapillary retinal nerve fiber layer thickness. RESULTS: A total of 102 patients, including 59(57.8%) patients with ICAS and 43(42.2%) patients without ICAS, were finally analysed in the study. The peripapillary retinal nerve fiber layer thickness (pRNFL) was reduced significantly in the average, the superior and the inferior quadrants of the ipsilateral eyes and in the superior quadrant of the contralateral eyes in patients with ICAS compared with patients without ICAS. After multivariate analysis, only the superior pRNFL thickness in the ipsilateral eyes was significantly associated with ICAS (OR,0.968; 95% CI,0.946-0.991; p = 0.006). The area under receiver operator curve was 0.679 (95% CI,0.576-0.782) for it to identify the presence of ICAS. The cut-off value of the superior pRNFL was 109.5 µm, and the sensitivity and specificity were 50.8% and 83.7%, respectively. CONCLUSION: The superior pRNFL in the ipsilateral eye was significantly associated with ICAS in this study. Larger studies are needed to explore the relation between pRNFL and ICAS further.


Assuntos
Arteriosclerose Intracraniana , Disco Óptico , Humanos , Células Ganglionares da Retina , Estudos Transversais , Constrição Patológica , Fibras Nervosas , Tomografia de Coerência Óptica/métodos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico
6.
Mediators Inflamm ; 2023: 2730841, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38131062

RESUMO

Background: Abdominal aortic occlusion (AAO) occurs frequently and causes ischemia/reperfusion (I/R) injury to distant organs. In this study, we aimed to investigate whether AAO induced I/R injury and subsequent damage in cardiac and neurologic tissue. We also aimed to investigate the how length of ischemic time in AAO influences reactive oxygen species (ROS) production and inflammatory marker levels in the heart, brain, and serum. Methods: Sixty male C57BL/6 mice were used in this study. The mice were randomly divided into either sham group or AAO group. The AAO group was further subdivided into 1-4 hr groups of aortic occlusion times. The infrarenal abdominal aorta was clamped for 1-4 hr depending on the AAO group and was then reperfused for 24 hr after clamp removal. Serum, hippocampus, and left ventricle tissue samples were then subjected to biochemical and histopathological analyses. Results: AAO-induced I/R injury had no effect on cell necrosis, cell apoptosis, or ROS production. However, serum and hippocampus levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) increased in AAO groups when compared to sham group. Superoxide dismutase and total antioxidant capacity decreased in the serum, hippocampus, and left ventricle. In the serum, AAO increased the level of inducible nitric oxide synthase (iNOS) and decreased the levels of anti-inflammatory factors (such as arginase-1), transforming growth factor- ß1 (TGF-ß1), interleukin 4 (IL-4), and interleukin 10 (IL-10). In the hippocampus, AAO increased the levels of tumor necrosis factor (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), IL-4, and IL-6, and decreased the level of TGF-ß1. In the left ventricle, AAO increased the level of iNOS and decreased the levels of TGF-ß1, IL-4, and IL-10. Conclusions: AAO did not induce cell necrosis or apoptosis in cardiac or neurologic tissue, but it can cause inflammation in the serum, brain, and heart.


Assuntos
Interleucina-10 , Traumatismo por Reperfusão , Camundongos , Masculino , Animais , Interleucina-4 , Interleucina-6/metabolismo , Espécies Reativas de Oxigênio , Fator de Crescimento Transformador beta1 , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/patologia , Interleucina-1beta , Fator de Necrose Tumoral alfa , Encéfalo/metabolismo , Necrose
7.
Int Ophthalmol ; 43(7): 2469-2475, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36976411

RESUMO

PURPOSES: We aimed to confirm the risk and risk factor for ischemic stroke after acute retinal arterial ischemia (ARAI). METHODS: A retrospective cohort study of patients with a diagnosis of acute retinal arterial ischemia (ARAI) and completing 2-year follow-up was conducted from January 2015 to December 2021 at a general hospital. RESULTS: A total of 69 patients including 43(62.3%) patients of central retinal artery occlusion (CRAO), 11(15.9%) patients of branch retinal artery occlusion (BRAO) and 15(21.7%) patients of ophthalmic artery occlusion (OAO) were included in the study. Patients age was 58.2 ± 13.0(years), male patients accounting for 51 (73.9%) and 22 (31.9%) patients having at least 70% ipsilateral carotid artery stenosis (ICAS). During the 2-years follow-up period, 11(15.9%) patients of ARAI experienced ischemic stroke. Among them, 3(20%) patients of OAO, 6(14%) patients of CRAO and 2(18.2%) patients of BRAO had ischemic stroke. The cumulative probabilities of ischemic stroke were 13.0% at 12.9 months and 15.9% at 24 months after ARAI. In addition, patients with at least 70% ICAS were more likely than patients without it to have ischemic stroke (p = 0.002). After Cox regression analysis, ICAS (≥ 70%) or occlusion was significantly associated with a high risk of ischemic stroke after ARAI during the 2-years follow-up time (HR,6.769,95%CI [1.792-25.578], p = 0.005). CONCLUSION: Patients have a high risk of ischemic stroke, particularly those with a diagnosis of ICAS (≥ 70%) or occlusion after the onset of ARAI. Clinical management of ARAI should focus on vascular risk factors control and secondary prevention for stroke.


Assuntos
AVC Isquêmico , Oclusão da Artéria Retiniana , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Estudos Retrospectivos , Retina , Oclusão da Artéria Retiniana/complicações , Oclusão da Artéria Retiniana/diagnóstico , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Isquemia/complicações , Isquemia/diagnóstico
8.
Stroke ; 51(8): 2568-2572, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32684142

RESUMO

BACKGROUND AND PURPOSE: The retina, as an externally located neural tissue, offers unique advantages in investigating the effect of therapeutic intervention on the brain. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates. METHODS: Acute retinal artery ischemia and reperfusion was induced by injecting an autologous clot into the ophthalmic artery of adult rhesus monkeys, and recanalization was achieved by focal thrombolysis with tPA (tissue-type plasminogen activator). Digital subtraction angiography and fluorescein angiography were used to evaluate blood flow in the retina and the choroid. Electroretinogram, optical coherence tomography, and hematoxylin and eosin staining were used to evaluate the structure and function of the retina after ischemia. RESULTS: Digital subtraction angiography and fluorescein angiography images confirmed occlusion of the ophthalmic and central retinal arteries, as well as recanalization after tPA thrombolysis. Electroretinogram indicated retinal functional damage following ischemia, and thrombolysis partially rescued its impairment. Optical coherence tomography and hematoxylin and eosin staining revealed ischemia-induced changes in the retina, and tPA partially mitigated these damages. CONCLUSIONS: This novel acute retinal artery ischemia and reperfusion model in rhesus monkeys may closely simulate retinal ischemia/reperfusion in clinical practice and provide an optimal platform for screening neuroprotective strategies.


Assuntos
Modelos Animais de Doenças , Oclusão da Artéria Retiniana/diagnóstico por imagem , Oclusão da Artéria Retiniana/cirurgia , Artéria Retiniana/diagnóstico por imagem , Artéria Retiniana/cirurgia , Angiografia Digital/métodos , Animais , Macaca mulatta , Masculino , Primatas , Reperfusão
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 964-969, 2020 Sep.
Artigo em Zh | MEDLINE | ID: mdl-32933627

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). METHODS: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. RESULTS: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). CONCLUSIONS: Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.


Assuntos
Miastenia Gravis , Tacrolimo/uso terapêutico , Atividades Cotidianas , Criança , Humanos , Imunossupressores , Miastenia Gravis/tratamento farmacológico , Recidiva Local de Neoplasia
10.
J Cell Physiol ; 234(8): 12637-12645, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30536714

RESUMO

Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony-stimulating factor (G-CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G-CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5-fluorouracil (5-FU) significantly limited the neuroprotection of RIPC or G-CSF treatment. The protein expression of proangiogenic factors such as Ang-2 was increased by ischemia, but treatment with either RIPC or G-CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke.


Assuntos
Isquemia Encefálica/fisiopatologia , Encéfalo/fisiopatologia , Circulação Colateral/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/metabolismo , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Pós-Condicionamento Isquêmico/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Monócitos/fisiologia , Neuroproteção/fisiologia , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/metabolismo
11.
Eur Neurol ; 80(5-6): 277-282, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30731463

RESUMO

BACKGROUND AND PURPOSE: Intravenous thrombolysis is known as the only effective reperfusion therapy for acute ischemic stroke (AIS) caused by small branches occlusion. However, it is still unclear whether intra-arterial thrombolysis (IAT) is safe and effective for patients without detectable arterial occlusion. This study evaluated the safety and efficacy of IAT in these patients. METHODS: Data were collected on consecutive patients from December 2012 to February 2017 at the Xuanwu Hospital, Capital Medical University. AIS patients without large artery occlusion during digital subtraction angiography (DSA) were divided into 2 groups: (1) Intra-arterial urokinase thrombolysis group (UK group): received intra-arterial urokinase thrombolysis treatment; (2) Control group: cerebral angiography examination only. The primary outcome was 3-month favorable functional outcome (modified Rankin Scale 0-2). RESULTS: A total of 48 patients received urokinase thrombolysis, and 34 patients underwent DSA examination only. The UK group had more frequent favorable functional outcomes (70.8 vs. 50%, p = 0.032) at 3-month follow-up and higher score of National Institutes of Health Stroke Scale improvement on the second day (p = 0.007). One patient (2%) had symptomatic intracerebral hemorrhage and 3 patients (6.3%) had asymptomatic intracerebral hemorrhage (asICH) in the UK group. One patient (3.3%) had asICH in the control group. There were no significant differences about ICH. CONCLUSIONS: AIS caused by small branches occlusion could benefit from intra-arterial urokinase thrombolysis, and the risk of intracerebral hemorrhage was not significantly higher.


Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Idoso , Angiografia Digital , Arteriopatias Oclusivas/patologia , Isquemia Encefálica/tratamento farmacológico , Angiografia Cerebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Terapia Trombolítica/métodos , Resultado do Tratamento
12.
Curr Neurol Neurosci Rep ; 15(1): 505, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25394858

RESUMO

Stroke is the second leading cause of death worldwide and a major cause of long-term severe disability representing a global health burden and one of the highly researched medical conditions. Nanostructured material synthesis and engineering have been recently developed and have been largely integrated into many fields including medicine. Recent studies have shown that nanoparticles might be a valuable tool in stroke. Different types, shapes, and sizes of nanoparticles have been used for molecular/biomarker profiling and imaging to help in early diagnosis and prevention of stroke and for drug/RNA delivery for improved treatment and neuroprotection. However, these promising applications have limitations, including cytotoxicity, which hindered their adoption into clinical use. Future research is warranted to fully develop and effectively and safely translate nanoparticles for stroke diagnosis and treatment into the clinic. This work will discuss the emerging role of nanotheragnostics in stroke diagnosis and treatment applications.


Assuntos
Nanopartículas/uso terapêutico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Sistemas de Liberação de Medicamentos , Humanos , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/fisiopatologia , Nanopartículas/efeitos adversos , Fármacos Neuroprotetores/administração & dosagem , Prognóstico , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
13.
Vis Neurosci ; 31(3): 245-52, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24735565

RESUMO

Limb remote ischemic conditioning (LRIC) provides a physiologic strategy for harnessing the body's endogenous protective capabilities against injury induced by ischemia-reperfusion in the central nervous system. The aim of the present study was to determine if LRIC played a role in protecting the retina from ischemia-reperfusion injury. A total of 81 adult male Sprague-Dawley rats were randomly assigned to sham and ischemia/reperfusion with or without remote LRIC arms. The retinal ischemic model was generated through right middle cerebral artery occlusion (MCAO) and pterygopalatine artery occlusion for 60 min followed by 1, 3, and 7 days of subsequent reperfusion. LRIC was conducted immediately following MCAO by tightening a tourniquet around the upper thigh and releasing for three cycles. Paraffin sections were stained with hematoxylin and eosin in order to quantify the number of cells in retinal ganglion cells (RGCs) layer throughout the duration of the study. Cellular expression of glial fibrillary acidic protein (GFAP) was detected and examined through immunohistochemistry. Protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was also analyzed by Western blot techniques. Our study demonstrated that the loss of cells in RGC layer was attenuated by LRIC treatment at 3 and 7 days following reperfusion (P < 0.05). Immunohistochemistry studies depicted a gradual increase (P < 0.05) in GFAP levels from day 1 through day 7 following ischemia and subsequent reperfusion, whereas LRIC reduced GFAP levels at 1, 3, and 7 days postreperfusion. In addition, LRIC increased the expression of Nrf2 and HO-1 at day 1 and 3 following ischemia/reperfusion. This particular study is the first remote conditioning study applicable to retinal ischemia. Our results strongly support the position that LRIC may be used as a noninvasive neuroprotective strategy, which provides retinal protection from ischemia-reperfusion injury through the upregulation of antioxidative stress proteins, such as Nrf2 and HO-1.


Assuntos
Infarto da Artéria Cerebral Média/complicações , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Doenças Retinianas/etiologia , Doenças Retinianas/prevenção & controle , Animais , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
14.
Brain Circ ; 10(1): 5-10, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655444

RESUMO

Ischemic stroke is a major global health crisis, characterized by high morbidity and mortality rates. Although there have been significant advancements in treating the acute phase of this condition, there remains a pressing need for effective treatments that can facilitate the recovery of neurological functions. Danggui-Shaoyao-San (DSS), also known as the Decoction of Chinese Angelica and Peony, is a traditional Chinese herbal formula. It has demonstrated promising results in the regulation of microglial polarization and modulation of neurosteroid receptor expression, which may make it a potent strategy for promoting the recovery of neurological functions. Microglia, which plays a crucial role in neuroplasticity and functional reconstruction poststroke, is regulated by neurosteroids. This review posits that DSS could facilitate the recovery of neuronal function poststroke by influencing microglial polarization through the neurosteroid receptor pathway. We will further discuss the potential mechanisms by which DSS could enhance neural function in stroke, including the regulation of microglial activation, neurosteroid regulation, and other potential mechanisms.

15.
Aging Dis ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502592

RESUMO

Retinal ischemia-reperfusion injury (RIRI) is a complex condition characterized by immune cell-mediated inflammation and consequent neuronal damage. This review delves into the immune response mechanisms in RIRI, particularly emphasizing the roles played by resident and peripheral immune cells. It highlights the pivotal role of microglia, the primary resident immune cells, in exacerbating neuroinflammation and neuronal damage through their activation and subsequent release of pro-inflammatory mediators. Additionally, the review explores the contributions of other glial cell types, such as astrocytes and Müller cells, in modulating the immune response within the retinal environment. The dual role of the complement system in RIRI is also examined, revealing its complex functions in both safeguarding and impairing retinal health. Inflammasomes, triggered by various danger signals, are discussed as crucial contributors to the inflammatory pathways in RIRI, with an emphasis on the involvement of different NOD-like receptor family proteins. The review further analyzes the infiltration and impact of peripheral immune cells like neutrophils, macrophages, and T cells, which migrate to the retina following ischemic injury. Critical to this discussion is the interplay between resident and peripheral immune cells and its implications for RIRI pathophysiology. Finally, the review outlines future research directions, focusing on basic research and the potential for clinical translation to enhance understanding and treatment of RIRI.

16.
Pediatr Neurol ; 160: 26-29, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39178650

RESUMO

BACKGROUND: Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients. METHODS: A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed. RESULTS: The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy. CONCLUSIONS: In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial.


Assuntos
Autoanticorpos , Humanos , Masculino , Feminino , Criança , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/sangue , Células de Purkinje/patologia , Células de Purkinje/imunologia , Fenótipo , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/fisiopatologia
17.
Brain Res ; 1842: 149098, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38942350

RESUMO

Ischemic stroke (IS) remains one of the most serious threats to human life. Early blood-brain barrier damage (BBB) is the cause of parenchymal cell damage. Repair of the structure and function of the BBB is beneficial for the treatment of IS. The traditional prescription ginseng aconitum decoction (GAD) has a long history in the treatment of cardiovascular and cerebrovascular diseases, however, the effect of GAD on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, in vitro models of BBB were established with brain endothelial cells (bEnd.3). We found that GAD reduced the leakage of the fluorescent probe FITC-dextran (P < 0.01) and increased the expression of tight junction proteins (Claudin-5, ZO-1) (P < 0.05) in the BBB model in vitro. Furthermore, to investigate the BBB protective effects of GAD in vivo. A total of 25 male C57/BL6 mice (20 - 22 g) were randomly divided into 5 groups (n = 5 per group): (1) Sham group (saline), (2) MCAO group (saline), (3) MCAO + CG group (Chinese ginseng 8 mg/kg/day), (4) MCAO + AC group (aconite 8 mg/kg/day), (5) MCAO + GAD group (GAD 8 mg/kg/day).We constructed IS model in mice and found that GAD treatment reduced IgG leakage (P < 0.05), up-regulated the expression of tight junction proteins Claudin-5, Occludin, and ZO-1 (P < 0.05). Further mechanism study showed that fatty acid oxidation (FAO) of vascular endothelial cells is involved in the protection of the BBB after IS, and GAD regulates FAO (P < 0.05) to protect BBB. In addition, we found the effect of GAD was stronger than that of Chinese ginseng (CG) (P < 0.05) and aconite (AC) (P < 0.01) alone. We concluded that GAD ameliorated the BBB dysfunction by regulating FAO involving vascular endothelial cells after IS. At the same time, the prescription is more effective than single traditional Chinese medicine.


Assuntos
Barreira Hematoencefálica , Medicamentos de Ervas Chinesas , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Masculino , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Camundongos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Aconitum , Proteína da Zônula de Oclusão-1/metabolismo , Claudina-5/metabolismo , Modelos Animais de Doenças , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Panax
18.
J Neurol ; 271(8): 4813-4825, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38869825

RESUMO

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke-heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research.


Assuntos
Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Síndrome
19.
CNS Neurosci Ther ; 30(2): e14631, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38358074

RESUMO

In the field of stroke thrombectomy, ineffective clinical and angiographic reperfusion after successful recanalization has drawn attention. Partial or complete microcirculatory reperfusion failure after the achievement of full patency of a former obstructed large vessel, known as the "no-reflow phenomenon" or "microvascular obstruction," was first reported in the 1960s and was later detected in both experimental models and patients with stroke. The no-reflow phenomenon (NRP) was reported to result from intraluminal occlusions formed by blood components and extraluminal constriction exerted by the surrounding structures of the vessel wall. More recently, an emerging number of clinical studies have estimated the prevalence of the NRP in stroke patients following reperfusion therapy, ranging from 3.3% to 63% depending on its evaluation methods or study population. Studies also demonstrated its detrimental effects on infarction progress and neurological outcomes. In this review, we discuss the research advances, underlying pathogenesis, diagnostic techniques, and management approaches concerning the no-reflow phenomenon in the stroke population to provide a comprehensive understanding of this phenomenon and offer references for future investigations.


Assuntos
Fenômeno de não Refluxo , Acidente Vascular Cerebral , Humanos , Fenômeno de não Refluxo/diagnóstico por imagem , Fenômeno de não Refluxo/etiologia , Fenômeno de não Refluxo/terapia , Microcirculação , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Reperfusão , Resultado do Tratamento
20.
Pediatr Neurol ; 152: 98-106, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242024

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is considered a demyelinating disease of the central nervous system, but an increasing number of encephalitis cases associated with MOG antibodies have been reported recently. METHODS: This was a single-center, retrospective study. All data for pediatric patients with MOGAD diagnosed at Beijing Children's Hospital from January 2017 to January 2022 were collected. Clinical characteristics and outcomes were analyzed, and treatment responses were compared between the rituximab (RTX) and mycophenolate mofetil (MMF) groups. RESULTS: A total of 190 patients (age range: 5 months to 16 years; median age: 7.2 years; females: 97) were included in this study. The phenotypes of the first attack included acquired demyelinating syndromes (105 [55%]), encephalitis other than acute disseminated encephalomyelitis (82 [43%]), and isolated meningitis (3 [2%]). After a median follow-up of 30.4 months (interquartile range: 14.8-43.7), 64 (34%) patients had relapses. Fifty-one of the 64 (80%) patients who had relapse received maintenance therapy, including MMF (41), RTX (11), maintenance intravenous immunoglobulin (two), and tocilizumab (two). The annualized relapse rates decreased significantly after treatment in both the RTX and MMF cohorts (P < 0.05); however, there were no significant differences between the two groups (P = 0.56). A total of 178 (94%) patients had complete (175 patients) or almost complete (three patients) recovery (modified Rankin scale [mRS] < 2), and 12 had moderate to severe deficits (mRS ≥ 2). CONCLUSIONS: The spectrum of pediatric MOGAD is broader than previously reported and includes demyelinating syndromes and encephalitis. Encephalitis is an important initial phenotype observed in pediatric patients with MOGAD.


Assuntos
Autoanticorpos , Encefalite , Feminino , Humanos , Criança , Lactente , Estudos de Coortes , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos , Encefalite/tratamento farmacológico , Rituximab/uso terapêutico , Recidiva , Ácido Micofenólico
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