"Stroke 1-2-0" is a Chinese numeric mnemonic linking face drooping, arm weakness, and speech difficulty to calling emergency services (1-2-0). We propose an enhanced repeated version-"Stroke 1-2-0, Stroke 1-2-0"-that adds visual impairment and imbalance to better detect posterior-circulation strokes, while repetition may boost recall and stresses zero delay in seeking help.
Background: The bidirectional relationship between Alzheimer's disease (AD) and periodontitis highlights a critical interface between oral and brain health, increasingly recognized as a key axis in aging-related degenerative diseases. This review synthesizes epidemiological, pathological, and mechanistic evidence underpinning their interconnected pathogenesis.
Results and conclusion: Epidemiologically, periodontitis is associated with an increased risk of AD, while AD patients exhibit a higher prevalence of periodontitis, driven by cognitive decline-impaired oral hygiene and synergistic inflammatory mechanisms. Pathologically, periodontal pathogens (e.g., Porphyromonas gingivalis) translocate to the brain via hematogenous, trigeminal, or oral-intestinal pathways, inducing neuroinflammation, β-amyloid (Aβ) aggregation, and tau hyperphosphorylation through virulence factors like gingipains and LPS. Conversely, AD-related neurodegeneration disrupts bone homeostasis to aggravate periodontitis via multiple mechanisms: (1) Aβ-mediated osteoclast activation through RAGE/NF-κB signaling and suppression of osteoblastogenesis; (2) autonomic nervous system dysregulation, where sympathetic hyperactivity promotes RANKL-dependent bone resorption; and (3) endocrine dysfunction, including HPA axis hyperactivation (chronic hypercortisolism), sex hormone deficiency, insulin resistance, and growth hormone/IGF-1 insufficiency, all of which perturb the balance between bone formation and resorption. Aging exacerbates this bidirectional interplay through immunosenescence (e.g., impaired neutrophil phagocytosis, senescent microglia) and inflammaging, creating a pro-degenerative milieu that amplifies both diseases. Clinical interventions, such as periodontal therapy and microbiota modulation, show promise in reducing systemic inflammation and slowing AD progression, though causal links require validation. Future research must prioritize longitudinal cohort studies, pathogen-specific mechanistic investigations, and translational strategies targeting the oral-brain axis to develop preventive interventions for aging populations.
Objective: This study aimed to evaluate the influence of anesthesia with propofol on epileptic discharges recorded by stereo-electroencephalography (SEEG) during pediatric epilepsy surgery.
Methods: We enrolled 30 pediatric patients (aged 2-14 years) undergoing epilepsy surgery between June 2022 and November 2023. SEEG recordings were obtained under different states of consciousness: awake, sleep, and anesthesia. We analyzed the power spectral density (PSD) across frequency bands and quantified the number of interictal spikes and high-frequency oscillations (HFO) including ripples and fast ripples (FRs).
Results: There was a significant reduction in the number of spikes, particularly within the seizure onset zone (SOZ), while ripples and FRs increased under general anesthesia, but the extent of the increase did not differ between the SOZ and other detected brain regions (NSOZ). Analysis of PSD showed increased energy during anesthesia, particularly in high-frequency bands. Meanwhile, no statistical differences were observed in energy changes between the SOZ and NSOZ when compared to wakefulness or sleep. HFOs emerged as more robust and consistent interictal biomarkers for localizing the SOZ under propofol anesthesia, particularly in the frontal cortex and cingulate cortex, and were not influenced by age.
Conclusions: General anesthesia with propofol significantly affects the number and frequency of epileptic discharges, particularly by reducing spikes while increasing HFOs. Notably, HFOs-particularly in the frontal and cingulate cortices-emerged as reliable biomarkers for delineating the SOZ and guiding surgical resections. Furthermore, no significant age-related variability was identified, supporting the applicability of intra-operative electroencephalography in pediatric epilepsy surgery.
Epilepsy is a common neurological disorder accompanied by mental and cognitive impairment, which affects approximately 50 million people worldwide. Recent studies revealed that transient receptor potential melastatin 8 (TRPM8) receptors exerted a significant effect in PTZ-induced acute seizure model. However, the exact function and mechanism of prefrontal TRPM8 receptor in seizures remain unclear. This study aimed to investigate the upstream and downstream signaling pathways of TRPM8 receptors and how they jointly regulate the occurrence and development of seizures.
Pentylenetetrazol (PTZ) was used to establish an acute mouse seizure model, and the seizure behavior of TRPM8 channel block mice and normal mice was observed and analyzed. Specific blocking of TRPM8 channels in specific brain regions was performed by stereotactic injection into the brain. The expression of TRPM8 downstream signaling molecules in the prefrontal cortex (PFC) and the apoptosis of neuronal cells were analyzed after PTZ-induced acute seizures.
TRPM8 receptors were upregulated in the PFC of mice with seizures. Inhibition or knockdown of TRPM8 in the PFC can effectively prolong the latency and reduce the level of seizures in mouse models induced by PTZ. Meanwhile, prefrontal TRPM8, Phosphorylated PKA (p-PKA) and Phosphorylated CREB (p-CREB) levels were upregulated during seizures. In the PTZ-induced acute seizure cell model, the expression of TRPM8, p-CREB, and p-PKA was also increased, but this effect was reversed by the TRPM8 inhibitor AMTB. PKA agonists significantly offset the effects of TRPM8 inhibitors in prolonging latency and reducing seizure levels. Finally, TUNEL staining showed that the apoptosis rate of prefrontal neurons in seizure mice decreased after TRPM8 inhibition and knockdown, while PKA activation could counteract the AMTB-induced decrease in neuronal apoptosis.
Prefrontal TRPM8 receptor plays a vital role in PTZ-induced acute seizures through the PKA/CREB pathway, which provides a potential target for the treatment of seizures.
The mechanical thrombectomy (MT) strategy obviously differs for acute middle cerebral artery occlusion (MCAO) stroke caused by embolism or atherosclerosis. Our study aimed to develop and validate a simple and universally applicable score for predicting etiology [embolism or intracranial arteriosclerosis (ICAS)] before MT in patients with acute MCAO stroke.
Between November 2019 and September 2022, we retrospectively enrolled eligible patients in our hospital as the training cohort. Additionally, consecutive patients between July 2023 and April 2024 were recruited as the validation cohort. Multivariate logistic regression analysis was used to identify the independent factors associated with etiology in the training group. Each factor was then point assigned based on β-coefficient, and a risk scoring system was developed. The scoring system was validated through the validation cohort. The C-statistic, Brier score, and Hosmer-Lemeshow test were used to assess model discrimination and calibration.
The training group and validation group finally included 277 patients (154 embolism-MCAO and 123 ICAS-MCAO) and 101 patients (59 embolism-MCAO and 42 ICAS-MCAO), respectively. A scoring system (AHOC score) covering four variables (atrial fibrillation, hyperdense middle cerebral artery sign, stenosis/occlusion in other arteries, and collateral status) was derived to help identify embolism-MCAO or ICAS-MCAO. The AHOC score showed good discrimination and calibration in the training cohort (C-statistic, 0.932 [0.902–0.963]; Brier score, 0.092 [0.070–0.115]; p value of the Hosmer-Lemeshow test, 0.604) and in the validation cohort (C-statistic, 0.933 [0.888–0.978]; Brier score, 0.102 [0.067–0.140]; p value of the Hosmer-Lemeshow test, 0.846). According to the AHOC score, patients with a score of 4–8 were identified as high-risk for the embolism-MCAO category. Conversely, a patient with a score of 0–3 was considered high-risk for the ICAS-MCAO category.
Our scoring system (AHOC score), consisting of atrial fibrillation, hyperdense middle cerebral artery sign, stenosis/occlusion in other arteries and collateral status, is a valid and applicable model for predicting the etiology in patients with acute MCAO before MT.
Blood–brain barrier (BBB) dysfunction serves as a critical driver of the secondary brain injury following intracerebral hemorrhage (ICH). Previous research has indicated that Apelin-13 demonstrates the potential to alleviate BBB dysfunction in various cerebrovascular disorders. However, the precise mechanisms through which Apelin-13 preserves BBB integrity remain elusive. This study investigated whether Apelin-13 exerted neuroprotective effects by targeting the Keap1/Nrf2 signaling.
An in vivo ICH model was established using collagenase. Neurological function, brain edema, tight junction protein levels, and Evans blue leakage were assessed. In vitro, bEnd.3 monolayers were induced by hemin to simulate ICH conditions. To assess the role of Apelin-13 in the Keap1/Nrf2 signaling, we employed specific shRNAs targeting Nrf2 and apelin receptor (APJ). The neuroprotective effects of Apelin-13 in hemin-stimulated bEnd.3 cells were assessed through transendothelial electrical resistance assay, western blotting, and immunofluorescence analysis.
Apelin-13 treatment significantly mitigated brain damage, reduced cerebral edema, and promoted neurological recovery in ICH mice. These effects were accompanied by a significant decrease in matrix metalloproteinase-9 expression and an increase in tight junction protein levels. Similar protective effects were observed in hemin-induced bEnd.3 cells, where Apelin-13 additionally promoted Nrf2 expression and suppressed Keap1 expression, suggesting the involvement of the Keap1/Nrf2 signaling. Critically, APJ silencing blocked the effects of Apelin-13 on the Keap1/Nrf2 pathway. Furthermore, Nrf2 knockdown eliminated the protective effects of Apelin-13, reversing its attenuation of apoptosis, preservation of tight junction integrity, and reduction of oxidative stress in hemin-stimulated bEnd.3 cells.
In conclusion, these findings demonstrate that through its engagement with APJ, Apelin-13 activates the endothelial Keap1/Nrf2 pathway to protect against ICH-induced BBB disruption and facilitate neurological recovery, highlighting its therapeutic promise for ICH.
Atherosclerosis is a chronic inflammatory disorder and a major cause of ischemic stroke. Immune-mediated mechanisms are increasingly recognized as central in this continuum, yet the global research landscape and its clinical translation remain insufficiently characterized.
We conducted a multi-level bibliometric analysis using the Web of Science Core Collection and MEDLINE. Searches targeted atherosclerosis, ischemic stroke, and immunity, restricted to English-language articles and reviews. After screening, 1760 WoSCC records and 708 human-only MEDLINE articles were analyzed with VOSviewer, CiteSpace, and Bibliometrix. Comparative assessment between China and the United States examined differences in research output, thematic focus, and methodological orientation.
Global publications rose steadily from 1999 to 2025, peaking in 2022. Inflammation, atherosclerosis, and ischemic stroke were the dominant themes, with growing interest in causal inference (e.g., Mendelian randomization) and translational biomarkers. China showed rapid post-2015 growth with focus on immune-cell mechanisms, while the United States maintained leadership in scholarly impact, clinical orientation, and collaboration. Human-only studies confirmed these patterns and highlighted emerging topics such as microRNAs, COVID-19, insulin resistance, and lipoprotein(a).
Research has shifted from associative links to mechanistic insights and early translational strategies. However, gaps remain between molecular and clinical domains, and causal pathways are underdeveloped. Future work should emphasize molecular–clinical integration, expand immunological targets, apply multi-omics and AI approaches, and strengthen international collaboration—particularly between China and the United States—to advance precision prevention and intervention in atherosclerotic ischemic stroke.
Mitochondria-associated endoplasmic reticulum membranes (MAMs) are specialized regions in cells where the endoplasmic reticulum and mitochondria closely interact. MAMs are enriched with a variety of proteins that regulate key cellular processes. These processes include mitochondrial fission and fusion, autophagy, lipid metabolism, calcium homeostasis, and oxidative stress. Increasing evidence suggests that disruption of MAMs structure and alterations in associated protein expression patterns are closely related to the pathogenesis of epilepsy.
This review synthesizes and analyzes current literature to outline the structural and functional roles of key MAMs proteins. It further examines experimental and clinical evidence linking MAMs dysregulation to epileptogenesis and treatment responses.
The analysis confirms that MAMs serve as a central hub coordinating cellular homeostasis. Specific alterations in MAMs structure and protein expression are consistently associated with epilepsy models. These alterations directly impact neuronal excitability, synaptic function, and cell survival pathways involved in disease progression.
Addressing these structural and functional properties of MAMs may provide valuable insights for developing novel therapeutic strategies for epilepsy.
Previous studies have indicated the potential benefits of tirofiban in preventing early neurological deterioration (END) in acute ischemic stroke (AIS) within 24 h of symptom onset. However, its efficacy and safety over a broader time window require further evaluation.
This multicenter study analyzed prospective data from AIS patients without large vessel occlusion (LVO), enrolled within 48 h of onset and with baseline NIHSS scores of 4–15. Participants received either intravenous tirofiban or oral antiplatelet therapy. The primary efficacy endpoint was the occurrence of END (increase in NIHSS score ≥ 2 points within 7 days). The primary safety endpoint was intracranial hemorrhage within 90 days. The study employed a combined analysis method of multivariable regression and propensity score matching (PSM).
Among 371 enrolled patients (198 in the tirofiban group, 173 in the oral antiplatelet group), compared with the oral antiplatelet group, the incidence of END in the tirofiban group was significantly lower, as indicated by multivariate regression analysis (9.6% vs. 18.0%, p = 0.038) and PSM (10.6% vs. 19.7%, p = 0.031). Both statistical methods indicated that intravenous tirofiban can significantly facilitate early neurological improvement in patients at 7 and 14 days (p < 0.05) and enhance the probability of a mRS score of 0–2 at 90 days (p < 0.05). Subgroup analysis indicated particular benefit for patients with branch atheromatous disease (BAD) (p = 0.041). No symptomatic intracranial hemorrhage occurred in either group.
For AIS patients without LVO, early intravenous tirofiban within 48 h of onset effectively reduced the risk of END and promoted early or long-term neurological improvement without increasing bleeding risk, suggesting a potential therapeutic benefit in an extended time window, especially for the BAD subtype.
Chinese Clinical Trial Registry (chictr.org.cn): ChiCTR2200061110.
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