Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke.

Ischemic stroke (IS) is the leading cause of disability and death worldwide. Owing to the aging population and unhealthy lifestyles, the incidence of cerebrovascular disease is high. Vascular risk factors include hypertension, diabetes, dyslipidemia, and obesity. Therefore, in addition to timely and effective reperfusion therapy for IS, it is crucial to actively control these risk factors to reduce the incidence and recurrence rates of IS. Evidence from human and animal studies suggests that moderate intermittent hypoxia (IH) exposure is a promising therapeutic strategy to ameliorate common vascular risk factors and comorbidities. Given the complex pathophysiological mechanisms underlying IS, effective treatment must focus on reducing injury in the acute phase and promoting repair in the recovery phase. Therefore, this review discusses the preclinical perspectives on IH conditioning as a potential treatment for neurovascular injury and highlights IH pre and postconditioning strategies for IS. Hypoxia conditioning reduces brain injury by increasing resistance to acute ischemic and hypoxic stress, exerting neuroprotective effects, and promoting post-injury repair and regeneration. However, whether IH produces beneficial effects depends not only on the hypoxic regimen but also on inter-subject differences. Therefore, we discuss the factors that may influence the effectiveness of IH treatment, including age, sex, comorbidities, and circadian rhythm, which can be used to help identify the optimal intervention population and treatment protocols for more accurate, individualized clinical translation. In conclusion, IH conditioning as a non-invasive, non-pharmacological, systemic, and multi-targeted intervention can not only reduce brain damage after stroke but can also be applied to the prevention and functional recovery of IS, providing brain protection at different stages of the disease. It represents a promising therapeutic strategy. For patients with IS and high-risk groups, IH conditioning is expected to develop as an adjunctive clinical treatment option to reduce the incidence, recurrence, disability, and mortality of IS and to reduce disease burden.

Dietary inflammatory potential, measured by the dietary inflammatory index (DII) has been linked to cognitive impairment. However, evidence was mostly driven by cross-sectional studies. This meta-analysis of prospective cohort studies aims to evaluate the relationship between DII and the risk of cognitive impairment, including mild cognitive impairment (MCI) and dementia. We conducted a systematic search of PubMed, Web of Science, and Embase for studies published up to July 25, 2024. Prospective cohort studies with adults aged 18 years or older, without dementia at baseline, and reporting the incidence of cognitive impairment by DII category were included. Data were analyzed using a random-effects model to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Nine prospective cohort studies with 266,169 participants were included. A high DII at baseline was associated with an increased risk of cognitive impairment during follow-up (RR: 1.34, 95% CI: 1.15-1.55, p < 0.001) with moderate heterogeneity (I² = 56%). Subgroup analyses revealed consistent associations across types of cognitive impairment (MCI, overall dementia, Alzheimer's disease) and study characteristics (p for subgroup difference all >0.05). Sensitivity analyses confirmed the robustness of the results. This meta-analysis suggests that a higher dietary inflammatory potential is independently associated with an increased risk of cognitive impairment. These findings underscore the potential impact of dietary inflammation on cognitive health and highlight the need for dietary strategies to mitigate cognitive decline risk.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [¹⁸F]-Fluoro-2-deoxy-2-d-glucose (¹⁸F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring ¹⁸F-FDG accumulation and ¹⁸F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of ¹⁸F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower ¹⁸F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher ¹⁸F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on ¹⁸F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

BACKGROUND: Several trials have shown the benefit and safety of endovascular therapy (EVT) compared with medical management (MM) of patients with a large ischemic core in the 90-day follow-up. However, the 1-year outcome comparison between EVT and MM in Asian patients with a large ischemic core has not been investigated. Our aim was to evaluate the 1-year outcomes of patients in the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core). METHODS: In this phase 3, randomized, open-label, blinded end point assessment trial, patients with anterior circulation large vessel occlusion and an Alberta Stroke Program Early CT Score of 3 to 5 or an infarct core volume of 70 to 100 mL were enrolled across 46 hospitals in China. Patients were randomly assigned 1:1 to EVT or MM. The 90-day outcomes were previously reported. We report a prespecified analysis of the ANGEL-ASPECT trial, with 1-year functional outcome as the primary outcome in this study. The primary outcome was the shift of the modified Rankin Scale (mRS) score (range, 0–6, with a higher score reflecting greater disability) to better outcomes at 1-year. The secondary outcomes included functional independence (mRS score, 0–2), independent ambulation (mRS score, 0–3), and mortality. This trial is registered with https://www.clinicaltrials.gov (Unique identifier: NCT04551664). RESULTS: One-year data were available for 425 of 455 (93%) patients for the primary outcome, with 214 patients in the EVT group and 211 in the MM group in the complete case analysis. The mean age was 66 years, and 38.1% were female. There was a greater likelihood of shift toward improved 1-year mRS distribution in the EVT compared with the MM group (generalized odds ratio, 1.25 [95% CI, 1.01–1.56]; P =0.04). Functional independence and independent ambulation were higher in the EVT compared with MM groups (mRS score, 0–2: 30.4% [65/214] versus 17.1% [36/211]; relative risk, 1.87 [95% CI, 1.27–2.75]; mRS score, 0–3: 50.0% [107/214] versus 35.6% [75/211]; relative risk, 1.46 [95% CI, 1.15–1.85], respectively). The 1-year mortality rate was 31.3% (67/214) in the EVT group and 26.5% (56/211) in the MM group (relative risk, 1.12 [95% CI, 0.82–1.53]). In addition, no change was found in the rate of functional independence between 90 days and 1 year in the EVT group (29.4% [69/214] versus 30.4% [65/214], respectively); however, a gain in functional independence was observed in the MM group from 90 days to 1 year (10.9% [26/211] versus 17.1% [36/211]), narrowing the magnitude of EVT treatment effect from 18.5% at 90 days to 13.3% at 1 year. CONCLUSIONS: In patients with large ischemic stroke from a proximal arterial occlusion presenting within 24 hours of onset, EVT reduced disability with durable 1-year benefit compared with MM. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04551664.

Purpose: Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design.Methods: We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis.Results: In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117–1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106–1.597, P = 0.002).Conclusions: Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.