Neurocritical Care最新文献

{"title":"Vagus Nerve Stimulation Attenuates Cognitive Impairment in Traumatic Brain Injury via the mtDNA/cGAS-STING/NLRP3 Inflammasome Axis.","authors":"Bingkai Ren, Junwei Kang, Xiaoyang Dong, Lianghua Huang, Xiao Wu, Yunliang Tang","doi":"10.1007/s12028-025-02351-9","DOIUrl":"10.1007/s12028-025-02351-9","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) is a major life-threatening event. In addition to neurological deficits, it can lead to long-term impairments of cognitive function. The vagus nerve (VN) provides a direct communication conduit between the central nervous system and the periphery, and modulation of the inflammatory reflex via electrical stimulation of the vagus nerve (VNS) shows efficacy in ameliorating pathology in neurodegenerative diseases. Our objective was to investigate the impact and underlying mechanism of VNS for cognitive impairment in a rat model of TBI.</p><p><strong>Methods: </strong>Male rats were implanted with VNS electrodes on the left VN 1 week prior to controlled cortical impact. Mitochondrial permeability transition pore blocker cyclosporin A (CsA) and stimulator of interferon genes (STING) agonist 2'3'-cGAMP were delivered by intranasal administration or intraventricular injection. Post-VNS assessments included Morris water maze, Nissl staining, hematoxylin and eosin staining, Western blotting, quantitative polymerase chain reaction, mitochondrial membrane potential, and enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>We found that VNS treatment significantly improved cognitive impairment, increased mitochondrial membrane potential, reduced accumulation of cytosolic mitochondrial DNA, attenuated cyclic GMP-AMP synthase (cGAS)-STING pathway, suppressed nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation, and partially reversed hippocampus neuronal damage and loss caused by TBI. However, 2'3'-cGAMP delivery significantly abrogated these effects of VNS. In addition, CsA also showed neuroprotective effects, including improved cognitive impairment, decreased levels of cGAS, phosphorylated STING, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved Caspase-1, ASC, and N-terminal Gasdermin D. CsA also inhibited interleukin-1β and interleukin-18 proinflammatory cytokine concentration.</p><p><strong>Conclusions: </strong>Stimulation of the VN attenuates the pyroptosis and neuroinflammatory cascades in the rat of the TBI model by regulating the mitochondrial DNA/cGAS/STING /NLRP3 pathway.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of Periostin in Acute Neuronal Apoptosis Induced by Subarachnoid Hemorrhage in Mice and its Suppression by Clarithromycin.","authors":"Hiroki Oinaka, Hideki Kanamaru, Fumihiro Kawakita, Yume Suzuki, Hideki Nakajima, Mai Nampei, Hidenori Suzuki","doi":"10.1007/s12028-025-02348-4","DOIUrl":"https://doi.org/10.1007/s12028-025-02348-4","url":null,"abstract":"<p><strong>Background: </strong>Periostin is an inflammation-related matricellular protein that has been reported to increase in the acute phase after subarachnoid hemorrhage (SAH) in clinical settings. However, its relationship with neuronal apoptosis, a characteristic of early brain injury, remains unknown. The purpose of this study was to investigate the involvement of periostin in SAH-induced acute neuronal apoptosis and to determine whether clarithromycin (CAM), a macrolide antibiotic known to suppress periostin expression, prevents acute neuronal apoptosis after SAH in mice.</p><p><strong>Methods: </strong>In 141 male C57BL/6 mice undergoing endovascular perforation SAH or sham operation, vehicle or CAM (50 mg/kg) was administered subcutaneously 5 min after surgery, followed by intracerebroventricular administration of vehicle or recombinant mouse periostin (R-periostin) 30 min after surgery. The intervention effects were assessed 24 h after surgery by neurological score, Western blotting, and double immunostaining.</p><p><strong>Results: </strong>After induction of SAH, neurological scores worsened, and caspase-3-dependent neuronal apoptosis was increased, which was associated with upregulation of periostin expression in the left (perforation side) cerebral hemisphere compared with sham-operated animals (p < 0.01 vs. sham + vehicle group, respectively). Administration of CAM improved neurological scores and reduced caspase-3-dependent neuronal apoptosis as well as periostin expression in SAH mice (p < 0.05, p < 0.01, p < 0.01 vs. SAH + vehicle group, respectively). The protective effects of CAM on neurological scores and neuronal apoptosis after SAH were counteracted by administration of R-periostin (SAH + CAM + vehicle group vs. SAH + CAM + R-periostin group, p < 0.05 and p < 0.001, respectively). Immunohistochemical analysis confirmed overexpression of periostin in neurons after SAH, which was attenuated by CAM treatment but re-increased by administration of R-periostin.</p><p><strong>Conclusions: </strong>These findings indicate that periostin-driven signaling contributes to caspase-dependent neuronal apoptosis during early brain injury after SAH. This study highlights periostin as a potential therapeutic target to attenuate SAH-induced acute neuronal apoptosis and demonstrates that CAM holds promise as an antiapoptotic agent through periostin inhibition.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Levetiracetam Dosing Optimization in Neurocritical Care Population: Neuro-ARC Study.","authors":"Maged Kharouba, Aaron M Cook, Melissa L Thompson Bastin, Demetrios J Kutsogiannis, Sherif Hanafy Mahmoud","doi":"10.1007/s12028-025-02347-5","DOIUrl":"https://doi.org/10.1007/s12028-025-02347-5","url":null,"abstract":"<p><strong>Background: </strong>Levetiracetam, a first-line antiseizure medication, is primarily eliminated through the kidneys, with approximately 66% renal elimination. Consequently, its pharmacokinetics are significantly influenced by kidney function. Augmented renal clearance (ARC), a condition characterized by renal hyperfiltration, is frequently observed in critical care settings and can profoundly impact the disposition of renally eliminated drugs such as levetiracetam. Our objectives were to characterize levetiracetam pharmacokinetics in neurocritical care patients, identify covariates significantly influencing drug clearance, and provide clinicians with optimal dosage recommendations in those with and without ARC.</p><p><strong>Methods: </strong>This was a multicenter, prospective, observational study involving patients admitted to the participating centers with life-threatening neurological illnesses. Each participant had up to four plasma samples collected, and the samples were analyzed using a validated high-performance liquid chromatography method. The creatinine clearance (CL_CR) of enrolled participants was measured using the 8-h urine collection method (measured  CL_CR [mCL_CR]). Population pharmacokinetic modeling was performed using Monolix software. Monte Carlo simulations were performed to explore various dosage strategies and to suggest optimal levetiracetam regimens.</p><p><strong>Results: </strong>Our study included 50 patients, with 35 patients (70%) experiencing ARC. Trough levetiracetam levels were significantly lower in the ARC group compared with the no-ARC group (median [interquartile range] 4.4 [11.5] vs. 11.8 [19] mg/L, p value = 0.039, respectively). Population pharmacokinetic modeling showed levetiracetam clearance at 4.6 ± 2.97 L/h and volume of distribution at 0.56 ± 0.63 L/kg, following a one-compartment model. The mCL_CR significantly affected levetiracetam clearance. Simulations indicated that an initial 500 mg twice daily (BID) dosage is insufficient. Patients with mCL_CR ≥ 90 mL/min/1.73 m², including patients with ARC, may need at least 1500 mg BID, whereas those with mCL_CR 60-89 mL/min/1.73 m² may require an initial dosage of 1250 mg BID.</p><p><strong>Conclusions: </strong>Augmented renal clearance significantly impacts the pharmacokinetics of levetiracetam by enhancing clearance. Dosing simulations revealed the inadequacy of the initial 500 mg BID regimen, indicating a minimum dosage of 1500 mg BID is necessary for patients experiencing ARC to achieve reference range concentrations.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Clinical Relevance of Blood Pressure Measures in Spontaneous Intracerebral Hemorrhage: A Post Hoc Analysis of ATACH-2.","authors":"Ravi Garg, Gabriel Torrealba-Acosta, Pitchaiah Mandava","doi":"10.1007/s12028-025-02350-w","DOIUrl":"https://doi.org/10.1007/s12028-025-02350-w","url":null,"abstract":"<p><strong>Background: </strong>Recent American Heart Association guidelines have relied on post hoc subgroup analyses to identify summary blood pressure measures for targets in early management of acute intracerebral hemorrhage. To our knowledge, measurement error has not been considered when determining the impact of these summary measures. Our objective was to determine whether statistically significant differences in three systolic blood pressure (SBP) measures (achieved SBP, SBP variability, and magnitude of SBP reduction) in patients with intracerebral hemorrhage from the antihypertensive treatment of acute cerebral hemorrhage II (ATACH-2) randomized clinical trial are clinically meaningful by comparing them to a minimally detectable difference (MDD) of 10 mm Hg.</p><p><strong>Methods: </strong>We performed a post hoc analysis of individual patient data from the ATACH-2 randomized clinical trial, evaluating the differences in achieved SBP, SBP variability, and magnitude of SBP reduction between patients with favorable (modified Rankin scale score 0-3) and unfavorable (modified Rankin scale score 4-6) outcomes. We used the empirical cumulative distribution functions and Kolmogorov-Smirnov tests to compare distributions, and we considered differences clinically meaningful if they exceeded the MDD of 10 mm Hg. We also performed a propensity score matched analysis to understand the nature of the association between these measures and outcomes.</p><p><strong>Results: </strong>Although SBP variability in the first 24 h differed statistically between outcome groups, the mean difference (95% confidence interval) did not exceed the MDD threshold. Achieved SBP and magnitude of SBP reduction showed no significant differences between groups. In the propensity score matched analysis, there were no statistical differences between any blood pressure measurements and outcomes.</p><p><strong>Conclusions: </strong>Our findings suggest that although there are statistically significant differences in SBP variability between patients with good and poor outcomes in ATACH-2, these differences do not meet the threshold for clinical relevance because they were within the range of measurement noise. The propensity score matched analysis suggested that the association between summary blood pressure measurements and outcomes is not robust to analytical method. These findings emphasize the need for caution in interpreting post hoc findings for clinical decision-making.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Protocolized Rehabilitation Versus Usual Care in Improving Functional Outcomes in Pediatric Neurocritical Patients: A Randomized Controlled Trial.","authors":"Aman Elwadhi, Prateek Kumar Panda, Amit Kumar Tyagi, Osama Neyaz, Amanjot Kaur, Lokesh Kumar Tiwari, Indar Kumar Sharawat","doi":"10.1007/s12028-025-02357-3","DOIUrl":"https://doi.org/10.1007/s12028-025-02357-3","url":null,"abstract":"<p><strong>Background: </strong>An early protocolized rehabilitation (EPR) program has the potential to improve functional outcomes in pediatric neurocritical care patients in the pediatric intensive care unit over standard care alone. However, this requires validation through a randomized controlled trial (RCT).</p><p><strong>Methods: </strong>This single-blind, parallel-design, two-arm RCT evaluated the efficacy of EPR in improving functional outcomes at 24 weeks in pediatric neurocritical patients aged 1-18 years compared to usual care. The study also aimed to compare adaptive function, gross motor function, language skills, cognition, behavioral issues, sleep patterns, quality of life, and family functional outcomes between the two groups. EPR was initiated within 72 h of mechanical ventilation and was customized for each patient by a team of specialists in pediatric neurology, physical medicine and rehabilitation, and speech and language pathology. Rehabilitation sessions were conducted daily for one week, then three times a week for one month, and monthly after discharge, supplemented with weekly teleconsultations.</p><p><strong>Results: </strong>A total of 196 patients were enrolled (98 in each arm). At 24 weeks, the Pediatric Cerebral Performance Category score was significantly better in the intervention arm (mean difference 0.133 [95% confidence interval 0.055-0.205], p < 0.001). Additionally, improvements were noted in the EPR arm across Child Behavior Checklist, Vineland Adaptive Behavior Scale, Children's Sleep Habits Questionnaire, Pediatric Quality of Life Inventory, and Family Assessment Device scores (p < 0.001 for all).</p><p><strong>Conclusions: </strong>EPR in pediatric neurocritical patients significantly improves functional outcomes and quality of life at 24 weeks compared to usual care.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to the Editor on \"Effect of Ketamine Analgosedation on Neurological Outcome in Patients with Severe Traumatic Brain Injury: A Randomized Controlled Pilot study\".","authors":"Sourav Burman, Charu Mahajan, Rajendra Singh Chouhan, Niraj Kumar","doi":"10.1007/s12028-025-02368-0","DOIUrl":"https://doi.org/10.1007/s12028-025-02368-0","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropalliative Care in the Emergency Department: Three Roles, One Goal.","authors":"Kristopher A Hendershot, Kei Ouchi","doi":"10.1007/s12028-025-02361-7","DOIUrl":"10.1007/s12028-025-02361-7","url":null,"abstract":"<p><p>Over the last decade, there has been an increased focus on incorporating palliative care principles into the practice of neurocritical care and emergency medicine (EM). In this article, we describe three different roles that EM clinicians can fill as they initiate the provision of primary neuropalliative care to neurocritically ill patients: the stage setter, the spokesperson, and the screener. As the stage setter, EM clinicians start to build trust with the family by \"breaking bad news\"; encouraging them to consider the patient's values, preferences, functional baseline, and directives; and providing support to the family during this emotional time as they hand them over to the admitting team who will continue this conversation. As the spokesperson, EM clinicians are involved in early treatment decisions, including whether the patient is admitted to the acute care service or the intensive care unit or transferred to a tertiary care facility, with the goal of preventing both the overuse and underuse of life-sustaining treatment. Lastly, as the screener, EM clinicians have a role to ensure that patients with chronic neurological diseases and patients with a medical history that puts them at high-risk of developing a neurological emergency have goals-of-care conversations and have acceptable control of their daily symptom burden. Further investigation is needed before interventions targeting the practice of neuropalliative care in the emergency department can be developed.</p>","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"KidsBrainIT: Visualization of the Impact of Cerebral Perfusion Pressure Insult Intensity and Duration on Childhood Brain Trauma Outcome\".","authors":"Muhammad Hasan, Muhammad Hammad Chola","doi":"10.1007/s12028-025-02343-9","DOIUrl":"https://doi.org/10.1007/s12028-025-02343-9","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Comments on \"KidsBrainIT: Visualization of the Impact of Cerebral Perfusion Pressure Insult Intensity and Duration on Childhood Brain Trauma Outcome\".","authors":"Bavo Kempen, Bart Depreitere, Ian Piper, Tsz-Yan Milly Lo","doi":"10.1007/s12028-025-02344-8","DOIUrl":"https://doi.org/10.1007/s12028-025-02344-8","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocritical Care Society Abstracts from the 23rd Annual Meeting 2025.","authors":"","doi":"10.1007/s12028-025-02334-w","DOIUrl":"10.1007/s12028-025-02334-w","url":null,"abstract":"","PeriodicalId":19118,"journal":{"name":"Neurocritical Care","volume":" ","pages":"1-244"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}