INTRODUCTION

While a 600 mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300 mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether higher clopidogrel LD regimen in percutaneous coronary intervention (PCI) outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease.

A systematic literature search for randomized clinical trials (RCTs) was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov and HerdinPH. Studies included those between 2010 and 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects.

Nine RCTs involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only eight studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced the incidence of overall MACE (OR: 0.82, 95% CI: 0.74-0.91, p = 0.0002), nonfatal myocardial infarction (OR: 0.56; 95% CI: 0.32-0.99, p = 0.15) and target vessel revascularization (OR: 0.63; 95% CI: 0.41-0.95, p = 0.03), without significant difference in terms of cardiac death (OR: 0.89; 95% CI: 0.76-1.04, p = 0.15) and stroke (OR: 0.92; 95% CI: 0.67-1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR: 1.27; 95% CI: 1.08-1.49, p = 0.005] without significant difference in minor bleeding (OR: 1.05; 95% CI: 0.94-1.17, p = 0.35).

The administration of 600 mg clopidogrel LD reduces the overall risk of MACE with associated increased risk of major bleeding.

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.

INTRODUCTION: Arrhythmias, especially atrial fibrillation (AF) and ventricular arrhythmias, are independent risk factors of mortality in patients with ischaemic heart disease (IHD). While there is a growing body of evidence that suggests an association between obstructive sleep apnoea (OSA) and cardiac arrhythmias, evidence on this relationship in patients with IHD has been scant and inconsistent. We hypothesised that in patients with IHD, severe OSA is associated with an increased risk of nocturnal arrhythmias. METHODS: We studied 103 consecutive patients with IHD who underwent an overnight polysomnography. Exposed subjects were defined as patients who had an apnoea-hypopnoea index (AHI) ≥30/h (severe OSA), and nonexposed subjects were defined as patients who had an AHI <30/h (nonsevere OSA). All electrocardiograms (ECGs) were interpreted by the Somte ECG analysis software and confirmed by a physician blinded to the presence or absence of exposure. Arrhythmias were categorised as supraventricular and ventricular. Arrhythmia subtypes (ventricular, atrial and conduction delay) were analysed as dichotomous outcomes using multiple logistic regression models. RESULTS: Atrial fibrillation and AF/flutter (odds ratio 13.5, 95% confidence interval 1.66-109.83; P = 0.003) were found to be more common in the severe OSA group than in the nonsevere OSA group. This association remained significant after adjustment for potential confounders. There was no significant difference in the prevalence of ventricular and conduction delay arrhythmias between the two groups. CONCLUSION In patients with IHD, there was a significant association between severe OSA and nocturnal AF/flutter. This underscores the need to evaluate for OSA in patients with IHD, as it may have important implications on clinical outcomes.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Atrial Fibrillation/diagnosis* ; Male ; Female ; Middle Aged ; Polysomnography ; Electrocardiography ; Myocardial Ischemia/complications* ; Aged ; Risk Factors ; Logistic Models

INTRODUCTION: Achieving low-density lipoprotein cholesterol (LDL-C) levels is key to preventing atherosclerotic cardiovascular events. However, many high-risk cardiovascular patients still experience poor LDL-C goal attainment and receive suboptimal lipid-lowering therapy (LLT) prescriptions. Herein, we evaluated LLT prescription patterns, LDL-C goal attainment and cardiovascular mortality among this population group in Singapore. METHODS: This prospective observational cohort study included 555 patients with ischaemic heart disease (IHD) admitted to the hospital in 2020. The LLT prescriptions, corresponding LDL-C levels and cardiovascular outcomes were assessed over a 24-month period. RESULTS: Most participants were male (82.3%), with 48.5% identified as Chinese. High-intensity statin prescriptions increased from 45.4% at hospital admission to 87.1% at discharge and remained stable at approximately 80% at 6, 12, and 24 months post-discharge. Combination LLT prescriptions increased from 12.3% at discharge to 33.8% by 24 months. Ezetimibe was the most commonly prescribed second-line LLT (40.8%), followed by inclisiran (1.09%) and anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapies (0.87%). Over 24 months, LDL-C goal attainment rates were 22.1% for LDL-C < 1.4 mmol/L and 47.2% for LDL-C < 1.8 mmol/L. Multivariable Cox proportional hazards regression indicated that achieving LDL-C < 1.8 mmol/L goal was associated with a reduction in all-cause mortality at 24 months (hazard ratio 0.53, 95% confidence interval 0.30-0.94, P = 0.030). CONCLUSION Treatment gaps in lipid management persist in 80% of the study population, indicating that statin monotherapy alone is insufficient to achieve LDL-C goals. Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative.
Humans ; Male ; Cholesterol, LDL/blood* ; Female ; Myocardial Ischemia/drug therapy* ; Middle Aged ; Prospective Studies ; Aged ; Singapore/epidemiology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Ezetimibe/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

OBJECTIVE: To explore the neuroprotective effect and underlying mechanism of Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) in the rat models of cerebral ischemia-reperfusion injury (CIRI) based on the p53 protein (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. METHODS: Of 102 male Wistar rats, 20 rats were randomly collected as a sham-operation group. Using a modified external carotid artery filament insertion method, CIRI models were prepared by occluding the middle cerebral artery in the rest rats. After modeling and excluding 1 non-successfully modeled rat and 1 dead one, the other modeled rats were randomized into a model group, an agonist group, an acupuncture group, and an acupuncture + agonist group, 20 rats in each one. Xingnao Kaiqiao acupuncture therapy was delivered in the rats of the acupuncture group and the acupuncture + agonist group. The acupoints included "Shuigou" (GV26), bilateral "Neiguan" (PC6), and "Sanyinjiao" (SP6) on the affected side. Electroacupuncture was attached to "Neiguan" (PC6) and "Sanyinjiao" (SP6) on the affected side, with dense-disperse wave, a frequency of 2 Hz/15 Hz and intensity of 1 mA. The intervention was delivered twice daily, 20 min each time and for 7 consecutive days. In the agonist group and acupuncture+agonist group, p53 agonist, COTI-2 was intraperitoneally injected (15 mg/kg), once daily for 7 consecutive days. Neurological deficit was evaluated using Zausinger's six-point scale. Cerebral infarction volume was quantified by triphenyl tetrazolium chloride (TTC) staining. Histopathological changes were observed using hematoxylin-eosin (HE) staining. Iron deposition was assessed by Prussian blue staining. Mitochondrial ultrastructure in the ischemic cortex was examined under transmission electron microscopy (TEM). Serum iron (Fe²⁺) was measured with chromometry. Malondialdehyde (MDA) and glutathione (GSH) levels in the ischemic hippocampus were determined using thiobarbituric acid and microplate assays, respectively. The mean fluorescence intensity of reactive oxygen species (ROS) in the ischemic cortex was analyzed by flow cytometry. The mRNA and protein expression of GPX4, SLC7A11, and p53 in the ischemic hippocampus were evaluated using quantitative real-time PCR (qRT-PCR) and Western blotting, respectively. RESULTS: Compared with the sham-operated group, the model group exhibited the decrease in neurological deficit score (P<0.01), and the increase in cerebral infarction volume percentage (P<0.01). The changes of brain tissue were presented in extensive cellular necrosis, pyknotic and deeply-stained nuclei, and vacuolar degeneration. The iron deposition was elevated in cortex and hippocampus (P<0.01), mitochondrial membrane density increased, the cristae was broken or reduced, and the outer membrane ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were elevated (P<0.01) and the level of GSH was reduced (P<0.01). The mRNA and protein expression of GPX4 and SLC7A11 was reduced (P<0.01), while that of p53 rose (P<0.01). When compared with the model group, in the agonist group, the neurological deficit score was reduced (P<0.05), the percentage of infarction volume was higher (P<0.01), the histopathological damage was further exacerbated, and the percentage of iron deposition increased in the cortex and hippocampus (P<0.01). The mitochondrial quantity decreased, the membrane density increased, the mitochondrial cristae were broken or reduced, and the outer membrane was ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were higher (P<0.01, P<0.05) and the level of GSH was reduced (P<0.05). The mRNA and protein expression of GPX4 and SLC7A11 decreased (P<0.01, P<0.05), while that of p53 was elevated (P<0.01). Besides, in comparison with the model group, the neurological deficit score was higher in the acupuncture group and the acupuncture + agonist group (P<0.01, P<0.05), the percentage of cerebral infarction volume was lower in the acupuncture group (P<0.01), the pathological damage of brain tissue was alleviated in the acupuncture group and the acupuncture + agonist group, and the percentage of iron depositiondecreased in the cortex and hippocampus (P<0.01). The mitochondrial structure was relatively clear, the mitochondrial cristae were fractured or reduced mildly in the acupuncture group and the acupuncture + agonist group. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were lower (P<0.01) and the level of GSH was higher (P<0.01) in the acupuncture group. The mean fluorescence intensity of ROS were dropped (P<0.01) in the acupuncture + agonist group. The mRNA expression of GPX4 and SLC7A11 was elevated (P<0.01) and that of p53 was reduced (P<0.01, P<0.05) in either the acupuncture group or the acupuncture + agonist group; the protein expression of GPX4 and SLC7A11 rose (P<0.05, P<0.01) and that of p53 was dropped (P<0.01) in the acupuncture group; and the protein expression of p53 was also lower in the acupuncture + agonist group (P<0.05). When compared with the agonist group, in the acupuncture + agonist group, neurological deficit score increased (P<0.01), the percentage of cerebral infarction volume decreased (P<0.01), the pathological brain tissue damage was reduced, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was relatively clear and the cristae broken or reduced slightly; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were dropped (P<0.01), while the level of GSH increased (P<0.05); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01). In comparison with the acupuncture + agonist group, in the acupuncture group, the neurological deficit score increased (P<0.05), the percentage of cerebral infarction volume decreased (P<0.05), the pathological brain tissue damage was alleviated, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was normal in tendency; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were reduced (P<0.05), while the level of GSH rose (P<0.01); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01, P<0.05). CONCLUSION Xingnao Kaiqiao acupuncture can alleviate neurological damage in CIRI rats, which is obtained probably by inhibiting ferroptosis through p53/SLC7A11/GPX4 pathway.
Animals ; Reperfusion Injury/metabolism* ; Male ; Acupuncture Therapy ; Rats ; Tumor Suppressor Protein p53/genetics* ; Brain Ischemia/metabolism* ; Rats, Wistar ; Signal Transduction ; Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Disease Models, Animal ; Acupuncture Points ; Amino Acid Transport System y+/genetics*

INTRODUCTION: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

BACKGROUND: Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke. METHODS: This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes. RESULTS: Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1-Q3: 20-88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12-0.49, P  <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11-0.41, P  <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08-0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06-0.50, P  <0.01). CONCLUSIONS: Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes. REGISTRATION ClinicalTrials.gov , NCT03222024.
Humans ; Male ; Female ; Prospective Studies ; Ischemic Stroke/mortality* ; Aged ; Middle Aged ; Aged, 80 and over ; Stroke ; Brain Ischemia

Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress