Remote ischemic conditioning reduces adverse events in patients with acute ischemic stroke complicating acute myocardial infarction: a randomized controlled trial.

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.

Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke.

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.

New insights into the roles of oligodendrocytes regulation in ischemic stroke recovery.

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.

Whole genome and exome sequencing identify NDUFV2 mutations as a new cause of progressive cavitating leukoencephalopathy.

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.

Evaluation of peripapillary retinal nerve fiber layer thickness in intracranial atherosclerotic stenosis.

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.

Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain.

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.

Risk and risk factor of ischemic stroke after acute retinal arterial ischemia.

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.

Novel Acute Retinal Artery Ischemia and Reperfusion Model in Nonhuman Primates.

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.

[Clinical effect of tacrolimus in the treatment of myasthenia gravis in children].

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.

Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation.

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.

Intra-Arterial Thrombolysis Improves the Prognosis of Acute Ischemic Stroke Patients without Large Vessel Occlusion.

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.

Nanotheragnostic applications for ischemic and hemorrhagic strokes: improved delivery for a better prognosis.

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.

Protective effects of remote ischemic conditioning against ischemia/reperfusion-induced retinal injury in rats.

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.

Immunological Landscape of Retinal Ischemia-Reperfusion Injury: Insights into Resident and Peripheral Immune Cell Responses.

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.

A narrative review of potential neural repair poststroke: Decoction of Chinese angelica and peony in regulating microglia polarization through the neurosteroid pathway.

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.

Ginseng aconitum decoction (Shenfu Tang) provides neuroprotection by ameliorating impairment of blood-brain barrier in cerebral ischemia-reperfusion injury.

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.

No-reflow after stroke reperfusion therapy: An emerging phenomenon to be explored.

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.

Stroke-heart syndrome: current progress and future outlook.

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.

The impact of high-altitude and cold environment on brain and heart damage in rats with hemorrhagic shock.

BACKGROUND: Hemorrhagic shock (HS) causes severe organ damage, worsened by high-altitude conditions with lower oxygen and temperatures. Existing research lacks specific insights on brain and heart damage under these conditions. This study hypothesizes that high-altitude and cold (HAC) environments exacerbate HS-induced damage in the brain and heart, aiming to improve treatment strategies. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats (200-250 g of weight) were randomly assigned into sham, HS + normal, HS + HAC (4,000 m), and HS + HAC (6,000 m). The HS model was established in SD rats (35% loss of total blood volume), and histopathological injuries of the brain and heart were detected using hematoxylin and eosin staining, Sirius red staining, and immunohistochemistry. Apoptosis of the brain and heart tissues was detected by terminal transferase-mediated dUTP nick end labeling (TUNEL) immunofluorescence staining. To determine the levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (Mcp-1), BCL2-associated X (BAX), and myeloid cell leukemia-1 (Mcl-1) protein, western blotting assay was used. RESULTS: The HAC environment induced pathological damage to the brain and heart and aggravated the degree of cardiac fibrosis in HS rats. However, it did not cause apoptosis of the brain and heart. In addition, it upregulated TNF-α, IFN-γ, Mcp-1, and BAX protein levels, but downregulated Mcl-1 protein levels (P < 0.05). CONCLUSIONS: The HAC environment aggravated the degree of brain and heart damage in HS rats, which may be related to neuron nucleus pyknosis, myocardial fibrosis, and inflammatory and apoptosis activation.

Predicting Futile Recanalization in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: The Role of White Blood Cell Count to Mean Platelet Volume Ratio.

BACKGROUND: Approximately half of AIS patients have an unfavorable outcome even after complete reperfusion. White blood cell (WBC) count to mean platelet volume (MPV) ratio (WMR) may be a promising predictive factor for futile recanalization. This study aimed to determine the predictive value of WMR in identifying individuals at higher risk of futile recanalization. METHODS: In this retrospective cohort study, 296 patients who achieved complete reperfusion after endovascular treatment (EVT) were included in the analysis. WBC count and MPV were collected at admission. Multivariable logistic regression was used to examine the independent association of the WMR with functional outcomes at three months. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were used to compare the accuracy of WMR for predicting futile recanalization. RESULTS: The adjusted odds ratios for the fourth quartile of WMR were 3.142 (95% CI 1.405- 7.027, P = 0.005) for unfavorable outcomes at 3 months in comparison with the first quartile. The inclusion of WMR in the traditional model enabled a more accurate prediction of unfavorable outcomes (NRI 0.250, P = 0.031; IDI 0.022, P = 0.017). CONCLUSION: Elevated WMR at admission was independently associated with futile recanalization among AIS patients who received EVT and might be useful in identifying futile recanalization.