This study aimed to investigate the effect of intravenous (IV) patient-controlled anesthesia (PCA) combined with dexmedetomidine (DEX) injections on reducing the risk of postoperative delirium (POD) in elderly patients undergoing thoracoscopic lung surgery, hypothesizing a potential risk reduction. Patients aged 65 years and older who underwent thoracoscopic lung surgery were assessed for eligibility. The participants were randomly assigned to either the test or control group. The test group received DEX through an IV PCA pump, consisting of 3 μg×kg-1 sufentanil and 3 μg×kg-1 DEX, while the control group received 3 μg×kg-1 sufentanil. PCA parameters were standardized, including a total volume of 150 mL, a 2-mL bolus dose with a 15-minute lock-out period, and a background infusion rate of 2 mL/h. The primary outcome was the incidence of POD, which was evaluated twice daily for 7 days after surgery. The secondary outcomes included duration of POD, incidence of postoperative nausea and vomiting (PONV), postoperative hospitalization duration, pain assessment, and adverse events. A total of 287 patients were recruited. The incidence of POD in the control group was significantly higher (15.28 vs. 4.9%, p=0.006). There were no significant differences in POD duration, PONV, or the length of hospital stay after operation between the two groups. The incidence of hypertension in the test group was significantly lower (p < 0.001), and no differences were found for other adverse events. IV patient-controlled DEX injections after major thoracoscopic lung surgery can reduce postoperative delirium.

Emergence delirium (ED) is a common complication in pediatric anesthesia. Although intranasal dexmedetomidine (DEX) is widely used, its application is constrained by a slow onset, residual risk of ED in some patients, and risks such as bradycardia and hypotension. Esketamine (ESK), an NMDA receptor antagonist, may provide a faster onset and reduce these side effects. This study compared the efficacy and safety of intranasal DEX-ESK combination versus DEX alone as premedication for anesthesia induction in pediatric patients undergoing surgery. Electronic databases (PubMed, Web of Science, Scopus, CINAHL, and Embase) were systematically searched for randomized controlled trials (RCTs). The primary outcomes included the ED incidence and the onset of sedation. Secondary outcomes included mask acceptance score, FLACC pain score, post-anesthesia care unit (PACU) length of stay, and adverse events. A random-effects model generated pooled effect estimates-risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. Prediction intervals were also reported to reflect the expected range of effects in future similar studies. Trial Sequential Analysis was performed. The certainty of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five RCTs encompassing 466 pediatric patients were included in the quantitative synthesis. The DEX-ESK combination was associated with a reduction in ED incidence (RR = 0.58; 95% CI: 0.35-0.97; p = 0.04) and a shorter time to sedation onset (MD = -3.95 min; 95% CI: -4.77 to -3.14; p < 0.01). Secondary analyses demonstrated improved mask acceptance (MD = -0.77; 95% CI: -1.27 to -0.27; p < 0.01), reduced FLACC pain scores (MD = -0.36; 95% CI: -0.70 to -0.02; p = 0.04), and shorter PACU length of stay (MD = -1.83 min; 95% CI: -2.75 to -0.91; p < 0.01). Adverse event incidence did not differ significantly between groups. The intranasal DEX-ESK combination was associated with improved outcomes compared with DEX monotherapy for pediatric premedication including reductions in ED incidence, a modest acceleration in sedation onset, improved mask acceptance, and slightly shorter PACU length of stay, without an increased risk of adverse events. This combination may represent a feasible and safe premedication option for pediatric patients. PROSPERO: CRD420251236740.

WTAP-regulated m6A modification contributes to cuproptosis in cardiomyocytes and diabetic cardiomyopathy.

Recent studies suggest that patients at intermediate-high risk of obstructive sleep apnea (OSA) are at greater risk of developing postoperative delirium (POD). The administration of dexmedetomidine (DEX) is suggested to prevent POD in the normal population. However, few studies have investigated the impact of DEX on POD in OSA patients. A prospective, randomized controlled trial will be conducted at a single center. Patients scheduled for elective laparoscopic surgery will be screened with the STOP-Bang questionnaire (SBQ). Patients who are intermediate-high risk for OSA (SBQ score ≥ 3) will be suggested to take a portable monitoring device for the diagnosis of OSA. Apner-Hyponea Index (AHI) values > 5/h are considered OSA. All the recruited OSA patients are randomly assigned to three treatment groups. The high dose of DEX group was treated with DEX at a loading dose of 0.5μg/kg over 10min followed by a maintenance dose of 0.2~0.7μg/kg/h. The low dose of DEX group was treated with DEX at a maintenance dose of 0.5μg/kg/h. The control group was not treated with DEX. POD was assessed using the 3-min diagnostic Confusion Assessment Method (3D-CAM) or the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) for 7 consecutive days or until discharge. We used the Richmond Agitation and Sedation Scale (RASS) to assess the level of sedation and drowsiness. The primary outcome will be the occurrence of POD. The secondary outcomes include pain at rest and provoked pain during postoperative day 1-7, length of stay (LOS) and postoperative complications within 30days. The result of this study will demonstrate whether the application of DEX could reduce the incidence of POD in OSA patients. We are of the conviction that the outcomes of this trial will afford a highly efficacious modality for preventing the occurrence of POD. Chinese Clinical Trial Registry ChiCTR2500108088. Registered on 25 August 2025.

Dexmedetomidine (DEX), a selective alpha-2 adrenergic receptor agonist, is widely used in various surgical settings, including cardiac and general surgeries, for its sedative, analgesic, and neuroprotective properties. Patients undergoing brain surgery are particularly susceptible to postoperative delirium (POD). Given the established benefits of dexmedetomidine in other surgical fields, its potential to mitigate delirium in neurosurgery warrants investigation. A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted from inception to January 2025 and updated in April 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed, and a meta-analysis was performed using Review Manager 5.4.1. Five randomized controlled trials were included, evaluating the efficacy of DEX in preventing POD in adult patients undergoing brain surgery. A total of 646 patients were enrolled, with DEX administered with a loading dose ranging from 0.5 to 1μg/kg over 10min, followed by a maintenance infusion rate of 0.1 to 0.5μg/kg/h during the surgical procedure. The pooled risk ratio (RR) for POD with DEX was 0.47 (95% confidence interval (CI): 0.35-0.63; p < 0.00001); reflecting a 53% reduction in the risk of postoperative delirium, with no statistical heterogeneity detected (χ2 = 2.09, degrees of freedom (df) = 4, p = 0.72; I2 = 0%). Subgroup analyses showed similar effect estimates across brain tumor and other cranial procedures. Adverse events were comparable between groups and generally mild. This meta-analysis found that perioperative dexmedetomidine was associated with a significant reduction in postoperative delirium risk in neurosurgical patients. Further multicenter trials are needed to confirm these findings and to refine optimal administration strategies.

Dexmedetomidine (DEX) has been consideredan effective adjunct to dental localanesthetics.Uncertaintyaboutits efficacy and safetyindental usestill remains. This study isprimarilydesignedtoevaluatethe effectiveness and safety of DEX as an adjunct to local anesthesia in dental procedures. This study followed PRISMA guidelines. The protocol was registered in PROSPERO (CRD420251035026). Outcomes were onset time, anesthesia duration, postoperative analgesia duration, post operative pain, sedation, and adverse events. Searches covered PubMed, Cochrane Library, Ovid, Embase, Web of Science, and Google Scholar. Risk of bias was assessed with Cochrane RoB 2 and ROBINS-I. RevMan 5.1 pooled mean differences and assessed heterogeneity. Sensitivity analyses and publication bias were examined in Comprehensive Meta-Analysis v3.7. Certainty of evidence was rated with GRADE. This meta-analysis encompassed sixteen controlled clinical trials comprising 658 participants. The addition of DEX decreased onset time by 48.78 s (95% CI: 64.22 to 33.35 s, p < 0.00001). This reduction is unlikely to be clinically significant in routine dental practice. DEX extended anesthesia duration by 31.10 min (95% CI: 13.77 to 48.43 min, p = 0.0004), and prolonged postoperative analgesic duration by 186.19 min (95% CI: 109.09 to 263.29 min, p < 0.00001), although both findings demonstrate substantial uncertainty due to unexplained heterogeneity (I2 = 94% and 99%, respectively). Hemodynamic evaluation revealed no clinically significant alterations in heart rate, intraoperative systolic and diastolic pressure, and oxygen saturation (p > 0.05 for all parameters). Minor variations in heart rate and blood pressure did not advance to hypotension or bradycardia. Dexmedetomidine as an adjunct to dental local anesthesia may reduce onset time, extend anesthesia duration, and postoperative analgesia with a favorable hemodynamic safety profile; however, substantial unexplained heterogeneity and modest sample size limit confidence in these estimates. Current evidence does not support routine clinical use; standardized, adequately powered trials are needed before definitive recommendations can be made.

Dexmedetomidine (DEX) seems to hold a potential neuroprotective role, possibly mediated by the attenuation of oxidative stress and neuroinflammation. This study aimed to delineate the effect of DEX used as an adjunct anaesthetic on cerebral oxygenation, cerebral injury and the release of inflammatory markers in brain tumour surgery. Fifty-six patients undergoing craniotomy for brain tumour excision were randomly assigned to receive either DEX (1 μg/kg for 10min and thereafter 0.7μg/kg/h) or placebo. Arterial and jugular-bulb blood samples were collected at predefined time-points, whereas a concomitant hemodynamic profile was obtained intraoperatively. S100B protein, neuron-specific enolase (NSE), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cortisol levels were determined at baseline and 6 and 24 h postoperatively. Demographic and perioperative characteristics were comparable between groups. Propofol consumption was considerably reduced in DEX-treated patients (p < 0.001). Measured (jugular-bulb oxygen saturation and partial pressure of oxygen) and estimated (oxygen and carbon dioxide arterial-jugular differences, brain oxygen extraction ratio) cerebral oxygenation indices were favourably affected by DEX infusion (p < 0.05), yet this effect was valid for 15 min (p < 0.05), corresponding to transient systemic hemodynamic augmentation. Moreover, postoperative S100B, NSE, TNF-α, IL-6 and cortisol levels were significantly attenuated in the DEX group (p < 0.01). DEX may attenuate the release of cerebral injury and neuroinflammation biomarkers and transiently improve hemodynamics and cerebral oxygenation during brain tumour surgery. Nonetheless, these surrogate effects do not establish clinically relevant neuroprotection, and potential dose-related hemodynamic instability warrants cautious, individualized use.

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) remains as a major contributor to death. This study evaluated the efficacy of intraoperative dexmedetomidine (DEX) infusion in reducing cerebral vasospasm incidence during endovascular intervention for aneurysmal SAH. A randomized, placebo-controlled, triple-blind research involved ninety individuals with unruptured aneurysmal SAH. Endovascular intervention participants were given either DEX at a loading dose of 0.5 μg/kg and a maintenance infusion of 0.2-0.6 μg/kg/h according to hemodynamics (heart rate, mean arterial pressure), or normal saline (0.9%) as a placebo, according to a random assignment. The rate of vasospasm was noticeably lower in the DEX group (13.33% vs. 33.33%, P=0.025) and the relative risk was 0.4 (95% CI 0.17-0.94). The time to first rescue analgesia was also longer in the DEX group (9.84±1.62 vs. 3.4±1.16 hours, P<0.001), and the total amount of morphine consumed in the first two days was noticeably lower in the DEX group (P<0.001). After thirty minutes, hemodynamic parameters were more stable. No significant differences were noted in cerebral infarction rates or adverse events, nor in the Extended Glasgow Outcome Scale (EGOS) at one month. Intraoperative DEX infusion significantly reduced vasospasm incidence while providing superior pain control and hemodynamic stability, without increasing adverse events. These findings suggest DEX as a promising adjunct for endovascular management of aneurysmal SAH.

Alzheimer's disease (AD) is a complex neurodegenerative condition involving β-amyloid (Aβ) deposition, tau abnormalities, neuroinflammation, neuronal degeneration, and progressive impairment of cognitive functions. Despite extensive research, effective disease-modifying therapies remain limited, highlighting the need for translationally relevant models and repurposable therapeutic candidates. Dexmedetomidine (DEX), an α2-adrenergic receptor agonist with known neuroprotective properties, was investigated in an adult zebrafish model of AD established through cerebroventricular administration of Aβ42. DEX treatment significantly reduced Aβ accumulation and was associated with reduced amyloidogenic gene expression, indicating transcriptional changes in amyloidogenic pathway-related genes. DEX attenuated neuroinflammation by reducing glial activation, lowering pro-inflammatory cytokine gene expression, and increasing expression of the anti-inflammatory gene il10. Immunofluorescence assessment further demonstrated reduced astrogliosis and preserved neuronal marker integrity, as indicated by increased HuC/D levels. Interestingly, DEX attenuated Aβ-induced proliferative responses, characterized by decreased PCNA expression, while enhancing cleaved caspase-3 levels, suggesting changes in proliferation and apoptotic signaling under Aβ stress conditions. Behavioral assessments further demonstrated that DEX alleviated Aβ42-induced anxiety- and aggression-like behaviors, improving behavioral phenotypes in this model. Overall, these findings underscore the multi-level effects of DEX in modulating AD-related pathological features. As a clinically available agent, DEX represents a promising candidate for repurposing in neurodegenerative disease contexts. Further preclinical studies in mammalian models are warranted to validate its translational relevance and therapeutic potential.

Complex regional pain syndrome (CRPS) is a form of chronic post-injury pain affecting the extremities with contributions from the somatic and sympathetic nervous systems. The mouse tibial fracture-cast model was developed to enable preclinical study of CRPS mechanisms and guide condition-specific drug development. Given the inherent limitations of reflex pain measures in mice, we sought to holistically characterize pain-like behaviors in this model in neutral and aversive environments using quantitative behavior analysis with LabGym, a user-friendly automation tool that requires no special equipment or extensive computational resources. Here, we show that tibial fracture-cast injury causes distinct changes in naturalistic and nocifensive behaviors in male and female mice in neutral and aversive environments, demonstrating reliable behavioral categorization using robust learning-based holistic assessment. As proof-of-concept for therapeutic testing, we leveraged this behavioral evaluation to characterize the peripheral versus central effects of targeting alpha-2 receptors (α2-AR) with dexmedetomidine (DEX), a selective α2-AR agonist with analgesic, sedative and anxiolytic properties. We found that DEX reduced mechanical allodynia primarily via central α2-ARs. DEX also decreased motion metrics, grooming and rearing in an open field, and distinctly affected the quality and quantity of grooming in an aversive environment, and systemic α2-AR antagonists did not suppress this effect. Importantly, we also determined that the sedative effects of DEX were attenuated in injured compared to uninjured mice, consistent with known sympathetic nervous system activation in CRPS. Overall, this study highlights the use of automated behavioral testing to parse analgesia from sedation in a unique preclinical pain model.

Dexmedetomidine (DEX) is increasingly used for neonatal sedation, but safety data remain limited. We conducted a single-center retrospective study including neonates receiving continuous DEX infusion. Cardiorespiratory events were extracted from bedside monitoring during the 8h before and the 24h after initiation. Hemodynamic and clinical parameters were analyzed, and autonomic activity was assessed using Newborn Infant Parasympathetic Evaluation (NIPE) monitoring in a subgroup. Thirty-seven infants (18 preterm, 19 term) were included; 86% received concomitant morphine. Bradycardia episodes increased after DEX initiation, particularly in preterm infants (p < 0.05). In contrast, hypotension, lactate levels remained unchanged, while urine output varied over time without a clinically meaningful reduction. Hypoxemic events decreased, while oxygen requirements remained stable. In the NIPE subgroup, heart rate decreased, with a trend toward increased NIPE values. DEX was associated with increased bradycardia without clear evidence of impaired hemodynamic or respiratory tolerance. These findings suggest an overall reassuring short-term safety profile and suggest a physiologically mediated sedative effect. What is Known: • Dexmedetomidine is increasingly used for sedationin preterm and term neonates, but cardiorespiratory safety data remain limited. • Bradycardia is the most frequently reported adverse effect. What is New: • Continuous monitor-derived data show increased bradycardia after dexmedetomidine initiation, without hypotension or impairedperfusion, while hypoxemic events decreased. • Autonomic monitoring (NIPE) suggests a trend toward increased parasympathetic activity, which may reflect modulation of autonomic balance under dexmedetomidine.

Age modifies the effect of dexmedetomidine on 28-day mortality in mechanically ventilated critically ill adults: A propensity score-weighted cohort study.

Dexmedetomidine (DEX) has emerged as a potential agent for sleep modulation; however, the effective doses required to induce multimodal electroencephalography (EEG)-defined sleep stages in patients with chronic insomnia remain unclear. This study aimed to quantify the cumulative DEX doses required to induce non-rapid eye movement (NREM) stage N2 and N3 sleep and to identify clinical predictors of dose variability. In this single-center retrospective cohort study, we analyzed 252 adults with chronic insomnia who underwent standardized intravenous DEX titration under continuous multimodal EEG monitoring. The primary outcomes were the cumulative DEX doses (µg) required to induce sustained N2 or N3 sleep. Univariable and multivariable linear regression models were used to identify independent predictors, including body mass index (BMI), depressive symptom severity assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS), and other clinically relevant covariates. Restricted cubic spline analyses were performed to examine potential nonlinear associations between BMI and DEX dose. Prespecified subgroup analyses stratified by age (<60 vs. ≥60 years) were conducted to assess effect modification. The median effective dose was 40µg (interquartile range [IQR], 33-48) for N2 sleep induction and 55µg (IQR, 48-64) for N3 sleep induction. BMI was independently associated with higher DEX dose requirements for both N2 (adjusted β = 0.71; 95% CI, 0.25-1.17; P = 0.003) and N3 sleep (adjusted β = 0.48; 95% CI, 0.07-0.89; P = 0.022). Higher MADRS scores were independently associated with increased DEX dose for N2 sleep induction (adjusted β = 0.17; 95% CI, 0.01-0.34; P = 0.041) but not for N3 sleep. Restricted cubic spline analyses demonstrated significant overall associations between BMI and DEX dose for both sleep stages, while tests for nonlinearity were not statistically significant. Age was not significantly associated with DEX dose requirements, and no significant interaction by age group was observed. In patients with chronic insomnia, higher cumulative doses of DEX are required to induce deeper NREM sleep stages. BMI is a key determinant of DEX dose requirements for both N2 and N3 sleep, whereas depressive symptom severity appears to selectively influence N2 sleep induction. These findings support the use of individualized, multimodal EEG-guided DEX titration strategies and provide preliminary data to inform future prospective dose-finding studies.

Dexmedetomidine mitigates postoperative delirium in aged mice via TFEB-linked restoration of microglial lysosomal function and attenuated neuroinflammation.

Sufficient sedation is important when performing an endoscopic submucosal dissection (ESD) for an esophageal squamous cell carcinoma (ESCC), and dexmedetomidine (DEX) is being increasingly used. ESD is often performed in elderly patients and those with comorbidities. Therefore, adverse events (AEs) in the circulatory and respiratory systems remain a clinical concern. Despite this, limited data exist on these AEs, so this study was conducted to investigate this issue. This single-center retrospective study included 526 patients who underwent ESD for ESCC under DEX-based sedation from 2016 to 2023. The study assessed the incidence of AEs in circulatory and respiratory systems, as well as the risk factors associated with these events. Various clinical factors, including the Prognostic Nutritional Index (PNI), were analyzed as candidates. Circulatory AEs occurred in 55 cases (10.5%), including bradycardia (7.2%) and hypotension (4.2%). Univariate and multivariate analyses revealed significant associations of lower PNI (<45) and prolonged procedure time with circulatory AEs (p=0.023 and p=0.008, respectively). Respiratory AEs occurred in 12 cases (2.3%), including respiratory depression (1.0 %) and post-ESD pneumonia (1.5 %) with one fatal case (0.2 %). An analysis of respiratory AEs showed that the elderly (≥80 years) and lower PNI were significant in univariate analysis but not in multivariate analysis (both p=0.07). When performing ESD for ESCC under DEX-based sedation, special caution is needed for patients with lower PNI and the elderly, who are more likely to experience circulatory or respiratory complications.

To explore the clinical efficacy and safety of dexmedetomidine hydrochloride for preoperative sedation in children undergoing emergency facial trauma cosmetic suturing. A total of 200 children with facial trauma admitted to the Emergency Surgery Department of our hospital from January to June 2025 were retrospectively enrolled and assigned to two groups for different sedation interventions. The study group received preoperative intranasal dexmedetomidine hydrochloride spray, while the control group received routine comfort care. The UMSS Sedation Scale was used to assess sedation level objectively, and rescue dosing protocols were implemented for sedation failure. Statistical analyses were performed using SPSS 30.0 software, with a two-tailed P-value ≤ 0.05 and 95% confidence intervals (CIs) considered statistically significant. A total of 100 cases were included in both the study group and the control group, with no baseline differences between the two groups (P > 0.05). The sedation failure rate in the study group was 8.0% (8/100), and all 8 cases achieved effective sedation after rescue dosing with one additional spray (15μg for 10.7-19.4 kg, 25 μg for 19.4-28.0 kg) intranasal dexmedetomidine hydrochloride; no sedation failure was observed in the control group. No serious adverse reactions were observed in either group. Preoperative and intraoperative cooperation in the study group was significantly better than that in the control group, and the incidence of agitation was significantly lower (P < 0.01), 95%CI: 0.0-0.2. No serious adverse reactions were observed in either group. Preoperative heart rate, respiratory rate, oxygen saturation, and mean arterial pressure were comparable between the two groups (P > 0.05). Intraoperatively, the study group maintained more stable vital signs, with significantly lower heart rate and mean arterial pressure than the control group (P < 0.05), 95%CI for heart rate: 8.2-15.7; 95%CI for mean arterial pressure: 5.1-10.3, all within normal physiological ranges. Preoperative intranasal dexmedetomidine hydrochloride is an effective and safe regimen for improving intraoperative cooperation, stabilizing vital signs, reducing agitation, and enhancing cosmetic suture quality and family satisfaction in children with emergency facial trauma.

Association of Dexmedetomidine Use With Complete Heart Block After Transcatheter Aortic Valve Replacement: A Retrospective Single-Center Cohort Study.

This study compared the wound-healing response and osteogenic gene expression profile of osteoblasts exposed to pediatric-equivalent concentrations of dexmedetomidine (DXMT) and propofol (POF). Human osteoblast-like SAOS-2 cells were assigned to control, low- and high-dose DXMT and POF groups based on pharmacokinetically derived free-drug levels. Scratch-wound closure was quantified over 24 h, and expression of osteogenesis- and cytoskeleton-related genes (RANKL, RUNX2, SP7, BMP2, VIM, VCL, OCN, ALP) was measured by SYBR Green quantitative Polymerase Chain Reaction (qPCR). Normality was assessed using the Shapiro-Wilk test, and group differences were analyzed with two-way ANOVA followed by Tukey's multiple comparisons test (p < 0.05). All groups demonstrated complete scratch closure by 24 h, with no differences at 6 h. At 18 h, POF did not differ from the control, whereas DXMT significantly accelerated closure at both doses in a dose-dependent fashion. High-dose DXMT significantly increased VIM (3.95 ± 3.12, p = 0.0144) and BMP2 (2.28 ± 0.70, p = 0.0002) expression, while RUNX2, SP7, and RANKL remained comparable to controls. ALP (1.68 ± 0.40, p = 0.0005) and OCN (3.31 ± 0.35, p = 0.0108) were significantly elevated only in the high-dose DXMT group, whereas POF showed no significant effects. At clinically relevant concentrations, DXMT was associated with enhanced scratch closure and increased expression of selected osteogenesis- and cytoskeleton-related genes in SAOS-2 cells, whereas POF showed limited effects under the tested conditions. These findings suggest that DXMT may influence early in vitro cellular responses relevant to bone healing and should be further validated in functional differentiation models and in vivo studies.

This study aimed to clarify the neuroprotective effect of dexmedetomidine (DEX) against cerebral ischemia reperfusion injury (CIRI) and its underlying mechanism using network pharmacology and in vivo validation. Network pharmacology was employed to explore the mechanism underlying DEX-mediated alleviation of CIRI. A rat CIRI model was established using the suture-occlusion method. Neurological scoring and behavioral assessments were conducted to evaluate neurological and motor functions; histological examination was performed to observe brain tissue and blood-brain barrier (BBB) injury. Western blotting and immunofluorescence analysis were utilized to assess the protein levels of factors associated with BBB integrity. Network pharmacology analysis revealed that DEX may exert a protective effect against CIRI through the AMPK/mTOR signaling pathway. DEX treatment significantly attenuated CIRI-induced impairments in neurological function and motor performance. Specifically, DEX upregulated the protein expression levels of P-AMPK/AMPK ratio, beclin 1, LC3 II/I, and ZO-1, whereas the P-mTOR/mTOR ratio and P62 were significantly downregulated, and cerebral tissue injury was alleviated. DEX exerts a significant protective effect against BBB injury in rats with CIRI. This neuroprotective effect is mediated by multiple synergistic mechanisms, including the upregulation of tight junction proteins and the regulation of the AMPK/mTOR signaling pathway. Collectively, the findings of the present study suggest that DEX represents a promising potential agent for the clinical treatment of CIRI-associated BBB impairment.

Objectives Following subarachnoid hemorrhage (SAH), long-lasting inflammation triggered by activated glial cells has adverse effects on neurological recovery. As an α2 adrenoceptor agonist commonly utilized for sedative purposes, dexmedetomidine (DEX) has demonstrated the ability to confer neuroprotective effects across diverse physiological or pathological conditions. This study was designed to determine whether DEX protects against SAH by altering astrocytic reactivity. Methods Eight-week-old male C57BL/6 mice were subjected to experimental SAH. They were treated with DEX in the presence or absence of the α2 adrenoceptor antagonist atipamezole (ATI) via intraperitoneal injection. Neurological function was evaluated on the basis of a modified Garcia score and beam balance test. TUNEL staining was conducted to assess neuronal apoptosis. Western blotting was carried out to determine the expression of Bcl-2, Bax, and cleaved caspase-3 in the hippocampus and ZO-1 and occludin in the cortex, and ELISA was conducted to measure TNF-α, IL-6, IL-1β, and HMGB1 expression. The wet‒dry method was employed to measure the water content in the brain tissue. The permeability of the blood‒brain barrier (BBB) was assessed via Evans blue staining. Primary astrocytes were treated with S100A4 and/or DEX. The expression levels of GFAP, C3, GBP2, Serping 1, PTX3, S100A10, S100A4, and the NF-κB pathway were also determined. Results DEX improved early neurological deficits in SAH mice, mitigated the permeability of the BBB, and reduced the brain water content. DEX attenuated neuronal apoptosis and proinflammatory cytokine (TNF-α, IL-6, IL-1β and HMGB1) expression in the cortex. However, DEX-mediated protective effects were attenuated by ATI administration. Additionally, DEX attenuated GFAP, C3, Serping1, S100A4, and NF-κB pathway activation in the brain and in S100A4-treated primary astrocytes, whereas ATI reversed the effects of DEX. Conclusion DEX has neuroprotective and anti-inflammatory effects in SAH through the inhibition of S100A4-mediated astrocytic “A1” polarization via the activation of the α2A adrenoceptor.