BACKGROUND AND OBJECTIVE

The incidence of ischemic stroke typically increases with age; however, recent studies have shown a concerning trend of stroke cases among adults under the age of 45. This neurologic condition is called “Stroke in the Young” (SITY). SITY poses public health concerns due to its long-term consequences on individuals and their families. Despite significant impact, published literature on SITY among Filipinos is scarce. Given the potential differences in genetic background and lifestyle, the clinical characteristics and outcomes of SITY Filipinos may vary considerably from other populations. Therefore, the aim of this study is to describe the clinical features and outcomes of ischemic SITY Filipinos.

The study was a two-center, five-year retro- spective cohort design involving 19- to 45-year-old  patients admitted between January 1, 2017, and December 31, 2022, diagnosed clinically and radiologically with ischemic stroke for the first time. Medical records were reviewed, including demographic data, stroke symptoms, cardiovascular or non-cardiovascular risk factors, and laboratory results. Ischemic stroke subtypes were categorized into cardioembolic, small artery occlusion, stroke of other determined causes, and stroke of undetermined cause through the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Functional outcomes on hospital discharge were assessed by the Modified Rankin Scale (mRS). All data were analyzed using descriptive statistics in the Statistical Package for the Social Sciences (SPSS software, version 29).

A total of 205 cases of ischemic SITY were chart reviewed. The mean age was 37.30, with a female predominance of 68.3%. The most reported cardiovascular risk factors were obesity (56.6%), hypertension (51.2%), heavy alcohol consumption (36.5%), and diabetes mellitus type 2 (19.5%). Concurrently, the non-cardiovascular risk factors identified were pregnancy, particularly in the postpartum period (4.8%), use of estrogen-containing pills (4.8%), and migraine without aura (4.4%). Based on TOAST classification, small vessel occlusion (42.1%) and large artery atherosclerosis (30.2%) were the most frequent ischemic stroke subtypes of SITY Filipino females. Mostly showed no symptoms of disability (35.1%) on hospital discharge.

This study highlights the difference in the clinical profile of young Filipino adults with ischemic stroke. Contrary to previous studies, ischemic stroke was more predominant among young females. Aside from hypertension, obesity has emerged as the leading cardio- vascular risk factor for ischemic SITY. Moreover, noncardiovascular risk factors, specific to females (pregnancy, use of estrogen-containing pills, and migraine), were also identified in the study. With regards to stroke subtypes, small vessel occlusion and large artery atherosclerosis were frequently seen in young female patients. These f indings suggest a need for gender-specific approaches in the evaluation, management, and prevention of ischemic SITY.

INTRODUCTION

Takayasu arteritis (TA) is a rare chronic large vessel vasculitis that affects the aorta and its major branches with a median age of onset of 25 years. The disease has a worldwide incidence of 1-2 per million, primarily affecting females with a 9:1 ratio. It is considered as an autoimmune disease that leads to progressive vessel thickening and stenosis, or aneurysmal dilatation. Coronary artery involvement is observed in 5.9%-58.2% of TA cases. We present a case of TA in a Filipino male presenting concurrently with myocardial infarction (MI) and ischemic stroke.

A 41-year-old Filipino male smoker with hypertension presented with chest pain, left-sided paresthesia and hemiparesis. Initial assessment revealed differential blood pressure between the arms, sensory and motor deficits, and abnormal ABI. Electrocardiogram confirmed anteroseptal ST-elevation MI and cranial computed tomography (CT) showed ischemic stroke. Arterial duplex scan had findings suggestive of hemodynamically significant lower extremity stenosis. A CT aortogram revealed multiple occlusions, including in the left subclavian artery, suggesting TA. Coronary angiography was attempted but was deferred due to peripheral arterial occlusion. A CT coronary angiogram revealed severe stenosis of the left anterior descending artery and moderate stenosis of the other coronaries. The patient was treated with dual antiplatelet therapy, statins, anticoagulation, corticosteroids and methotrexate. He experienced significant improvement in neurological symptoms and was chest pain-free upon discharge. At the 1-month follow-up, the patient remained asymptomatic.

Coronary involvement in TA can manifest as angina, MI, or other coronary lesions. The coexistence of MI and ischemic stroke in the same event is rare. Traditional risk factors for ischemic heart disease (IHD) in this patient such as hypertension and smoking may have contributed to the presentation, though TA itself is known to accelerate atherosclerosis. Limited vascular access hindered coronary intervention in this case and revascularization strategies remain challenging in active TA. The formation of extensive collateral arteries, along with early initiation of immunosuppressive therapy, likely contributed to the patient’s survival.

This case illustrates a rare and complex case of TA in a male patient with concurrent MI and ischemic stroke. Although coronary revascularization was not pursued due to occluded access, immunosuppressive therapy successfully managed the patient’s condition. Extensive collateral artery formation and early therapeutic intervention were key factors in the patient’s favorable outcome.

Objective To explore macrophage subpopulations in ischemic stroke (IS) by using single-cell RNA sequencing (scRNA-seq) data analysis and High-Dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA). Methods Based on single-cell sequencing data, transcriptomic information for different cell types was obtained, and macrophages were selected for subpopulation identification. hdWGCNA, cell-cell communication, and pseudotime trajectory analysis were used to explore the characteristics of macrophage subpopulations following IS. Key genes related to IS were identified using microarray data and validated for diagnostic potential through Receiver Operating Characteristic (ROC) analysis. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential functions of these genes. Results The scRNA-seq data analysis revealed significant changes in macrophage subpopulation composition after IS. A specific macrophage subpopulation enriched in the stroke group was identified and designated as MCAO-specific macrophages (MSM). Pseudotime trajectory analysis indicated that MSM cells were in an intermediate stage of macrophage differentiation. Cell-cell communication analysis uncovered complex interactions between MSM cells and other cells, with the CCL6-CCR1 signaling axis potentially playing a crucial role in neuroinflammation. Two gene modules associated with MSM were identified via hdWGCNA, significantly enriched in pathways related to NOD-like receptors and antigen processing. By integrating differentially expressed MSM genes with conventional transcriptomic data, three IS-related hub genes were identified: Arg1, CLEC4D, and CLEC4E. Conclusion This study reveals the characteristics and functions of macrophage subpopulations following IS and identifies three hub genes with potential diagnostic value, providing novel insights into the pathological mechanisms of IS.
Macrophages/metabolism* ; Computational Biology/methods* ; Single-Cell Analysis/methods* ; Transcriptome ; Ischemic Stroke/metabolism* ; Animals ; Gene Regulatory Networks ; Gene Expression Profiling ; Humans ; Male

Objective To explore the effects of Shuanglu Tongnao Formula on neuroinflammation in ischemic stroke (IS) rats via the P2X purinoceptor 7 receptor (P2X7R)/NLR family pyrin domain-containing 3 (NLRP3) pathway. Methods The rats were divided into five groups: the IS group, control group, Shuanglu Tongnao Formula group, P2X7R inhibitor brilliant blue G (BBG) group, and Shuanglu Tongnao Formula combined with P2X7R activator adenosine triphosphate (ATP) group, with 18 rats in each group. Except for the control group, rats in all other groups were used to construct an IS model using the suture method. After successful modeling, the drug was given once a day for 2 weeks. Neurological function scores and cerebral infarction volume ratios were measured in rats. Pathological examination of the ischemic penumbra brain tissue was performed. Immunofluorescence staining was used to quantify the proportions of microglia co-expressing both inducible nitric oxide synthase (iNOS) and ionized calcium-binding adapter molecule 1 (Iba1), as well as arginase 1 (Arg1) and Iba1, in the ischemic penumbra brain tissue. ELISA was used to detect tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6) and IL-10 in the ischemic penumbra brain tissue. Western blotting was used to measure P2X7R, NLRP3, and IL-1β proteins in the ischemic penumbra brain tissue. Results Compared with the control group, the IS group showed disordered neuronal arrangement, nuclear condensation, and obvious infiltration of inflammatory cells in the ischemic penumbra; significantly elevated neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with reduced proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. Compared with the IS group, the Zhuang medicine Shuanglu Tongnao Formula and BBG groups demonstrated alleviated brain tissue damage; reduced neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with increased proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. ATP reversed the effects of Zhuang medicine Shuanglu Tongnao Formula on microglial polarization and neuroinflammation in IS rats. Conclusion Zhuang medicine Shuanglu Tongnao Formula may promote the transformation of microglia from M1 type to M2 type by inhibiting the P2X7R/NLRP3 pathway, thereby improving neuroinflammation in IS rats.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Ischemic Stroke/pathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Brain Ischemia/drug therapy* ; Microglia/metabolism*

PROPOSE: To investigate the molecular mechanisms underlying the protective effects of ischemic preconditioning (IPC) in patients undergoing total knee arthroplasty. METHODS: GSE21164 was extracted from an online database, followed by an investigation of differentially expressed genes (DEGs) between IPC treatment samples at 2 time points (T0T and T1T). Function and pathway enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed to identify hub genes according to 5 different algorithms, followed by enrichment analysis. In addition, long noncoding RNAs (lncRNAs) were identified between the T0T and T1T samples. Furthermore, a competing endogenous RNA network was predicted based on the identified lncRNA-messenger RNA (mRNA), lncRNA-microRNA (miRNA), and mRNA-miRNA relationships revealed in this study. Finally, a drug-gene network was investigated. Statistical analyses were performed using GraphPad Prism 8.0. Differences between groups were determined using an unpaired t-test. p < 0.05 was considered significant. RESULTS: A total of 343 DEGs at T0 and 10 DEGs at T1 were identified and compared with their respective control groups, followed by 100 DEGs between T0T and T1T. Based on these 100 DEGs, protein-protein interaction network analysis revealed 9 hub genes, mainly with mitochondria-related functions and the carbon metabolism pathway. Six differentially expressed lncRNAs were investigated between T0T and T1T. A competing endogenous RNA network was constructed using 259 lncRNA-miRNA-mRNA interactions, including alpha-2-macroglobulin antisense RNA 1-miR-7161-5p-iron-sulfur cluster scaffold. Finally, 13 chemical drugs associated with the hub genes were explored. CONCLUSION Iron-sulfur cluster scaffold may promote IPC-induced ischemic tolerance mediated by alpha-2-macroglobulin antisense RNA 1-miR-7161-5p axis. Moreover, IPC may induce a protective response after total knee arthroplasty via mitochondria-related functions and the carbon metabolism pathway, which should be further validated in the near future.
Humans ; Arthroplasty, Replacement, Knee ; Ischemic Preconditioning ; RNA, Long Noncoding/genetics* ; Protein Interaction Maps ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Gene Regulatory Networks

BACKGROUND

Thrombolysis, or the administration of intravenous recombinant tissue plasminogen activator (IV rTPA) within the narrow therapeutic window following ischemic stroke onset, has emerged as a critical intervention in acute stroke care with the potential to restore blood flow and improve chances of functional recovery.

This study aimed to describe the demographic profile, risk factors, ischemic stroke subtypes, clinical course, and outcomes of stroke thrombolysis in a tertiary hospital in the Philippines over the past five years. It also aimed to evaluate key performance indicators in terms of benchmark times in the administration of IV rTPA.

This study used a retrospective observational design including all adult acute ischemic stroke patients who received IV rTPA at the University of the Philippines - Philippine General Hospital (UP-PGH). Data was collected through census and chart review.

One hundred eighty-eight patients received IV rTPA, majority were males (57.45%) with a median age of 60 years old. Hypertension (76.60%) was the most common risk factor for ischemic stroke. Partial anterior circulation infarcts (67.55%) and large artery atherosclerosis (49.47%) were the most common ischemic stroke subtype and etiology, respectively. The median door to needle time was 48 minutes, and the median length of hospital stay was five days. There was improvement in median NIHSS from 13 to 4, with a median modified Rankin scale of 3 indicating moderate disability upon discharge. Less than five percent (4.79%) had symptomatic intracerebral hemorrhage. The inhospital all-cause mortality rate among thrombolysed patients was 13.83%, mostly from non-neurologic causes. Nosocomial pneumonia and the need for neurosurgical interventions after thrombolysis were significantly associated with poor outcome (p < 0.05).

Our findings support the use of IV rTPA in the treatment of acute ischemic stroke. Existing stroke protocols in our institution are able to achieve the recommended thrombolysis benchmark times, leading to better functional outcomes for stroke patients.

Endovascular thrombectomy (EVT) has revolutionized the management of acute ischemic stroke (AIS) caused by large-vessel occlusion, significantly improving outcomes worldwide. This single-center case series evaluated the early outcomes of EVT in AIS patients treated at this institution, focusing on its implications within a low- or middleincome country setting. The study aimed to assess the feasibility, safety, and efficacy of EVT, analyzing premorbid comorbidities, time to treatment, revascularization rates, procedural complications, and clinical outcomes. Five consecutive cases of AIS due to large-vessel occlusion treated with EVT were analyzed. The patients in this series were aged 21 to 75 years, all with a baseline modified Rankin Scale (mRS) score of 0. The average NIH Stroke Scale (NIHSS) score on admission was 17. Four patients received Alteplase before EVT within four hours of symptom onset. Successful recanalization (TICI 2b-3) was achieved in all cases. Post-thrombectomy, two patients developed re-occlusion, with one resulting in mortality. Among the patients, 40% achieved a favorable outcome, defined as a modified Rankin Scale (mRS) score of 2 at three months. This initial experience demonstrates promising results in achieving successful recanalization and improving clinical outcomes in AIS patients with large-vessel occlusion. However, the study also highlights challenges such as procedural complications and post-thrombectomy re-occlusion, underscoring the need for ongoing evaluation and optimization of patient selection and procedural protocols in lowresource settings. Future studies with larger sample sizes are warranted to further validate these findings and refine EVT protocols tailored to local healthcare contexts.

We describe an unusual case of hypoxic ischemic encephalopathy in a preterm female of 36 weeks who presented with status epilepticus and atypical abdominal myoclonus. The seizures were confirmed electrographically using video electroencephalography (EEG), while the abdominal myoclonus was demonstrated to be nonepileptic, as it had no EEG correlate. Other possible causes of neonatal seizures were excluded. The infant then responded to a gamut of antiseizure medications but the myoclonus persisted. To the best of our knowledge, this is the first report of atypical myoclonus in a preterm baby caused by hypoxic ischemic encephalopathy.

Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator (tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory treatments. Small-molecule natural medicines, particularly those derived from traditional Chinese herbs, have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke (AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.
Humans ; Ischemic Stroke/physiopathology* ; Animals ; Neuroprotective Agents/therapeutic use* ; Drugs, Chinese Herbal/chemistry* ; Biological Products/therapeutic use* ; Stroke/drug therapy*

Ischemic stroke (IS) is a prevalent neurological disorder often resulting in significant disability or mortality. Resveratrol, extracted from Polygonum cuspidatum Sieb. et Zucc. (commonly known as Japanese knotweed), has been recognized for its potent neuroprotective properties. However, the neuroprotective efficacy of its derivative, (E)-4-(3,5-dimethoxystyryl) quinoline (RV02), against ischemic stroke remains inadequately explored. This study aimed to evaluate the protective effects of RV02 on neuronal ischemia-reperfusion injury both in vitro and in vivo. The research utilized an animal model of middle cerebral artery occlusion/reperfusion and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion to simulate ischemic conditions. The findings demonstrate that RV02 attenuates neuronal mitochondrial damage and scavenges reactive oxygen species (ROS) through mitophagy activation. Furthermore, Parkin knockdown was found to abolish RV02's ability to activate mitophagy and neuroprotection in vitro. These results suggest that RV02 shows promise as a neuroprotective agent, with the activation of Parkin-mediated mitophagy potentially serving as the primary mechanism underlying its neuroprotective effects.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mitophagy/drug effects* ; Resveratrol/analogs & derivatives* ; Neuroprotective Agents/pharmacology* ; Humans ; Neurons/metabolism* ; Reactive Oxygen Species/metabolism* ; Ischemic Stroke/genetics* ; Male ; Quinolines/pharmacology* ; Mice ; Fallopia japonica/chemistry* ; Mitochondria/metabolism* ; Reperfusion Injury/metabolism* ; Rats ; Mice, Inbred C57BL ; Disease Models, Animal