Frontiers in stroke最新文献

{"title":"Overcoming barriers in the implementation of stroke care rehabilitation in a public hospital in Costa Rica","authors":"Beatriz Coto-Solano","doi":"10.3389/fstro.2024.1366957","DOIUrl":"https://doi.org/10.3389/fstro.2024.1366957","url":null,"abstract":"Stroke is a major public health concern in developing countries, where the burden of the disease is high and resources for care are often limited. While progress has been made in improving stroke care, many barriers still exist in providing adequate rehabilitation care for stroke survivors. In this paper we study the case of Costa Rica and how stroke care has been addressed in recent years. It is important to consider the particularities of Costa Rica when working on stroke rehabilitation. The existence of a socialized healthcare system, along with the consolidation of acute stroke management protocols, allows for the adequate management of the early stages. In addition to this, families play a key role in rehabilitation, particularly for a country where there is a lack of medium stay and long-stay rehabilitation centers. Therefore, providing training and education for families is essential in stroke case management. Looking toward the future, there is still a pending need to generate homogeneous stroke rehabilitation protocols throughout the national healthcare system, to ensure equitable access to health care, and to consolidate multidisciplinary groups. At the same time, the implementation of technologies is urgent, particularly considering their potential to help reduce waiting lists. Another goal is enhancing coordination with other state entities and NGOs to advance community, labor or educational reintegration of stroke patients.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140213652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subarachnoid hemorrhage-associated brain injury and neurobehavioral deficits are reversed with synthetic adropin treatment through sustained Ser1179 phosphorylation of endothelial nitric oxide synthase","authors":"W. Dodd, Devan Patel, D. Laurent, Brandon Lucke-Wold, K. Hosaka, Richard D. Johnson, Nohra Chalouhi, Andrew A. Butler, Eduardo Candelario-Jalil, B. Hoh","doi":"10.3389/fstro.2024.1371140","DOIUrl":"https://doi.org/10.3389/fstro.2024.1371140","url":null,"abstract":"Subarachnoid hemorrhage (SAH) is a life-threatening vascular condition without satisfactory treatment options. The secreted peptide adropin is highly expressed in the human brain and has neuroprotective effects in brain injury models, including actions involving the cerebrovasculature. Here, we report an endothelial nitric oxide synthase (eNOS)-dependent effect of synthetic adropin treatment that reverses the deleterious effects of SAH.We tested the molecular, cellular, and physiological responses of cultured brain microvascular endothelial cells and two mouse models of SAH to treatment using synthetic adropin peptide or vehicle.SAH decreases adropin expression in cultured brain microvascular endothelial cells and in murine brain tissue. In two validated mouse SAH models, synthetic adropin reduced cerebral edema, preserved tight junction protein expression, and abolished microthrombosis at 1 day post-SAH. Adropin treatment also prevented delayed cerebral vasospasm, decreased neuronal apoptosis, and reduced sensorimotor deficits at seven days post-SAH. Delaying initial treatment of adropin until 24 h post-SAH preserved the beneficial effect of adropin in preventing vasospasm and sensorimotor deficits. Mechanistically, adropin treatment increased eNOS phosphorylation (Ser1179) at 1 & 7 days post-SAH. Treating eNOS−/− mice with adropin failed to prevent vasospasm or behavioral deficits, indicating a requirement of eNOS signaling.Adropin is an effective treatment for SAH, reducing cerebrovascular injury in both the acute (1 day) and delayed (7 days) phases. These findings establish the potential of adropin or adropin mimetics to improve outcomes following subarachnoid hemorrhage.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"30 1‐2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140228136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors of stroke literacy among African Americans in the “buckle of the stroke belt”","authors":"N. A. Sunmonu, Angela M. Malek, Carolyn Jenkins, H. Hyacinth","doi":"10.3389/fstro.2024.1331085","DOIUrl":"https://doi.org/10.3389/fstro.2024.1331085","url":null,"abstract":"Stroke is associated with racial disparities in morbidity and mortality and stroke outcomes. Stroke literacy is a significant predictor of on-time arrival to the emergency room for acute stroke treatment. In this study, we examined sociodemographic and socioeconomic factors that predict key aspects of stroke literacy: knowledge of stroke signs/symptoms and intent to call 911 in the event of a stroke.We analyzed archived data from a survey of African American adults over 18 years residing in the “buckle of the stroke belt.” Participants were ranked into 2 categories: low or no and moderate to adequate stroke knowledge. Then we performed univariate and multivariable analyses to determine the independent predictors of (1) knowledge of stroke signs and symptoms and (1) intent to call 911.Participants aged 18–39 years (OR = 0.46, 95% CI: 0.27– 0.80) were more likely to correctly recognize stroke signs and symptoms compared to those who are 65 years and above. Those age 40–64 years were also more likely to recognize stroke signs and symptoms compared to those who are 65 years and above. On the other hand, those with less than high school (OR = 2.83, 95% CI: 2.03–3.96) or complete high school education (OR = 1.95, 95% CI: 1.28–2.96) were less likely to recognize stroke signs and symptoms. Males were less likely (OR = 0.65, 95% CI: 0.64–0.66) to report that they would call 911 in the event of a stroke. While respondents aged 40–64 years (OR = 1.87, 95% CI: 1.14–3.09) and those with moderate to adequate knowledge of stroke (OR = 1.39, 95% CI: 1.18–1.65) were more likely to call 911 in the event of a stroke. Socioeconomic status was generally associated with stroke literacy.Among resident of the “buckle of the stroke belt,” we observed that age, sex, and educational level are among the key predictors of knowledge of stroke signs and symptoms and intent to call 911 in the event of a stroke. Stroke literacy and educational programs needs to incorporate these key sociodemographic aspects as a strategy for improving literacy and reduce stroke-related disability and health disparities.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"32 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140426434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-hospital telestroke and expanded hyper-acute telestroke network solutions to reduce geographic inequities: a brief review from the South Pacific","authors":"Anna Ranta, Heinrich J. Audebert, Luatupu Ioane-Cleverley","doi":"10.3389/fstro.2024.1338003","DOIUrl":"https://doi.org/10.3389/fstro.2024.1338003","url":null,"abstract":"Hyper-acute stroke treatments are time sensitive, and decision-making is complex. Telemedicine has been highly effective in breaking down regional access barriers by providing front line rural hospital clinicians with remote telemedicine decision support by remote stroke experts. With the advent of mechanical thrombectomy, hyper-acute stroke care has grown even more complex from both a decision-making and logistical perspective. Mobile Stroke Units (MSU) have been deployed in a few urban settings globally but are unlikely to address all global access issues due to geographical and logistical factors. This paper reviews the feasibility and benefit of extending telestroke into the pre-hospital setting as an adjunct or alternative to MSUs. It will discuss how this service model can fit into existing stroke networks and potential deployment strategies. Finally, the paper also considers potential scalability of pre- and in-hospital telestroke support across regional and international boundaries to further reduce global hyper-acute access inequities.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"27 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140438453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity in genetic risk of recurrent stroke: a genome-wide association study meta-analysis","authors":"Chad M. Aldridge, N. Armstrong, N. A. Sunmonu, Christopher Becker, Deepak Palakshappa, Arne G Lindgren, A. Pedersen, T. Stanne, C. Jern, J. Maguire, Fang-Chi Hsu, Keith L. Keene, Michèle Sale, M. Irvin, B. Worrall","doi":"10.3389/fstro.2024.1338636","DOIUrl":"https://doi.org/10.3389/fstro.2024.1338636","url":null,"abstract":"Stroke is a leading cause of death and disability worldwide. Recurrent strokes are seven times more lethal than initial ones, with 54% leading to long-term disability. Substantial recurrent stroke risk disparities exist among ancestral groups. Notably, Africans face double the risk and higher fatality rates compared to Europeans. Although genetic studies, particularly GWAS, hold promise for uncovering biological insights into recurrent stroke, they remain underexplored. Our study addresses this gap through meta-analyses of recurrent stroke GWAS, considering specific ancestral groups and a combined approach.We utilized four independent study cohorts for African, European, and Combined ancestry recurrent stroke GWAS with genotyping, imputation, and strict quality control. We harmonized recurrent stroke phenotype and effect allele estimates across cohorts. The logistic regression GWAS model was adjusted for age, sex, and principal components. We assessed how well genetic risk of stroke informs recurrent stroke risk using Receiver Operating Characteristic (ROC) curve analysis with the GIGASTROKE Consortium's polygenic risk scores (PRS).Harmonization included 4,420 participants (818 African ancestry and 3,602 European ancestry) with a recurrent stroke rate of 16.8% [median age 66.9 (59.1, 73.6) years; 56.2% male]. We failed to find genome-wide significant variants (p < 5e−8). However, we found 18 distinct suggestive (p < 5e−6) genetic loci with high biological relevance consistent across African and European ancestries, including PPARGC1B, CCDC3, OPRL1, and MYH11 genes. These genes affect vascular stenosis through constriction and dilation. We also observed an association with SDK1 gene, which has been previous linked with hypertension in Nigerian and Japanese populations). ROC analysis showed poor performance of the ischemic stroke PRS in discriminating recurrent stroke status (area under the curve = 0.48).Our study revealed genetic associations with recurrent stroke not previously associated with incident ischemic stroke. We found suggestive associations in genes previously linked with hypertension. We also determined that knowing the genetic risk of incident stroke does currently not inform recurrent stroke risk. We urgently need more studies to understand better the overlap or lack thereof between incident and recurrent stroke biology.","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"56 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140442233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-brain barrier disruption mediates the association between cerebral small vessel disease and clinical outcome after stroke: a secondary analysis of the Lesion Evolution in Stroke and Ischemia on Neuroimaging study.","authors":"Derrick N Okine, Kyle C Kern, Marie Luby, Lawrence L Latour, Rebecca F Gottesman","doi":"10.3389/fstro.2024.1510359","DOIUrl":"10.3389/fstro.2024.1510359","url":null,"abstract":"<p><strong>Introduction: </strong>White matter hyperintensities (WMH) in patients presenting with acute ischemic stroke are associated with worse clinical outcomes, but the mechanisms underlying this association are unclear. The purpose of this study was to determine whether blood-brain barrier (BBB) disruption, detected as the hyperintense acute reperfusion marker (HARM) on post-gadolinium follow-up FLAIR MRI, is associated with WMH and mediates the association between WMH and stroke outcomes.</p><p><strong>Methods: </strong>This is a secondary analysis of the LESION study, where patients with suspected acute ischemic stroke who were candidates for acute stroke intervention or had a baseline NIHSS ≥ 4 underwent serial multimodal MRI within 24 hours of last-known-well time, and again at 2 or 24 hours. WMH were visually graded on baseline FLAIR for presence and severity (minor or moderate-severe). HARM was evaluated on post-gadolinium FLAIR for presence and severity (minor, severe focal or severe diffuse). Using binomial and multinomial logistic regression, we tested whether WMH grade was associated with presence or severity of HARM, covarying for demographics, vascular risk factors, and stroke characteristics in sequential models. Finally, we used structural equation models to test the mediation effects of severe HARM on the association between WMH and stroke outcomes, including discharge NIHSS, hemorrhagic transformation, and 90-day modified Rankin scale.</p><p><strong>Results: </strong>For 213 stroke patients (mean age 70 years, 54% female), higher WMH grade was associated with increased risk for severe diffuse HARM (OR:3.37, 95% CI: 1.45-7.81), although not after adjusting for vascular risk factors or stroke characteristics. In our univariate model, severe HARM had a partial mediating effect between WMH and discharge NIHSS, explaining 23% of the association.</p><p><strong>Discussion: </strong>These findings suggest a possible association between severe diffuse HARM and WMH severity. The relationship between WMH severity and early stroke outcome may be mediated by blood-brain barrier disruption.</p>","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Financial analysis of a locomotor exercise trial for post-stroke recovery: insights from the HIT Stroke Trial.","authors":"Emily M Hazen, Bria L Bartsch, Sandra A Billinger","doi":"10.3389/fstro.2024.1425385","DOIUrl":"10.3389/fstro.2024.1425385","url":null,"abstract":"<p><strong>Background: </strong>Navigating the complexities of post-stroke recovery trials requires addressing challenges in participant recruitment and retention and effective resource management to ensure trial success. The aim of this study was to examine the financial requirements associated with conducting the Moderate-Intensity Exercise vs. High-Intensity Interval Training to Recover Walking Post-Stroke (HIT Stroke Trial) at a single site encompassing a wide catchment area, recognizing the intricate challenges of participant recruitment and retention inherent in post-stroke recovery trials.</p><p><strong>Methods: </strong>To determine cost, study expense reports were gathered and divided into seven categories: recruitment, screening assessments, baseline assessments, intervention, outcome assessments, retention, and oversight. Categories were then further divided into chronological order for initial contact and prescreening, consenting, initial screening, and baseline testing. The 12-week intervention was divided into 4-week blocks: intervention block 1, post 4-week outcome testing, intervention block 2, post 8-week outcome testing, intervention block 3, and post 12-week outcome testing.</p><p><strong>Results: </strong>Total direct cost for site execution was $539,768 with cost per participant approximated as $35,984. Oversight costs accounted for 65.8% of the budget at $355,661. To achieve goals related to inclusive participant recruitment ($21,923) and retention ($28,009), our site costs totaled $49,932. Direct study-related costs included screening assessments ($5,905), baseline assessments ($15,028), intervention ($76,952), and outcome assessments ($36,288).</p><p><strong>Discussion: </strong>Clinical trials focusing on walking rehabilitation and exercise, particularly those requiring multiple assessment visits, demand rigorous oversight. This cost analysis provides important and critical insight into the expenses required to successfully execute an exercise-based walking rehabilitation trial in the United States.</p>","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocognitive impairment in Ugandan children with sickle cell anemia compared to sibling controls: a cross-sectional study.","authors":"Paul Bangirana, Amelia K Boehme, Annet Birabwa, Robert O Opoka, Deogratias Munube, Ezekiel Mupere, Phillip Kasirye, Grace Muwanguzi, Maxencia Musiimenta, George Ru, Nancy S Green, Richard Idro","doi":"10.3389/fstro.2024.1372949","DOIUrl":"10.3389/fstro.2024.1372949","url":null,"abstract":"<p><strong>Introduction: </strong>The neurocognitive functions in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment.</p><p><strong>Methods: </strong>This cross-sectional study of the neurocognitive functions in children with SCA (<i>N</i> = 242) and non-SCA siblings (<i>N</i> = 127) used age- and linguistically appropriate standardized tests of cognition, executive function, and attention for children ages 1-4 and 5-12. Test scores were converted to locally derived age-normalized <i>z</i>-scores. The SCA group underwent a standardized stroke examination for prior stroke and transcranial Doppler ultrasound to determine stroke risk by arterial flow velocity.</p><p><strong>Results: </strong>The SCA group was younger than their siblings (mean ages 5.46 ± 3.0 vs. 7.11 ± 3.51 years, respectively; <i>p</i> < 0.001), with a lower hemoglobin concentration (7.32 ± 1.02 vs. 12.06 ± 1.42, <i>p</i> < 0.001). The overall cognitive SCA <i>z</i>-scores were lower, -0.73 ± 0.98, vs. siblings, -0.25 ± 1.12 (<i>p</i> < 0.001), with comparable findings for executive function of -1.09 ± 0.94 vs. -0.84 ± 1.26 (<i>p</i> = 0.045), respectively. The attention <i>z</i>-scores for ages 5-12 for the SCA group and control group were similar: -0.37 ± 1.4 vs. -0.11 ± 0.17 (<i>p</i> = 0.09). The overall differences in SCA status were largely driven by the older age group, as the <i>z</i>-scores in the younger subsample did not differ from controls. Analyses revealed the strongest predictors of poor neurocognitive outcomes among the SCA sample to be the disease, age, and prior stroke (each <i>p</i> < 0.001). The impacts of anemia and SCA were indistinguishable.</p><p><strong>Discussion: </strong>Neurocognitive testing in children with SCA compared to non-SCA siblings revealed poorer SCA-associated functioning in children older than age 4. The results indicate the need for trials assessing the impact of disease modification on children with SCA.</p>","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High wall shear stress-dependent podosome formation in a novel murine model of intracranial aneurysm.","authors":"Jiayi Lu, Mengjun Dai, Yuanqing Yan, Louise D McCullough, Yan-Ning Rui, Zhen Xu","doi":"10.3389/fstro.2024.1494559","DOIUrl":"https://doi.org/10.3389/fstro.2024.1494559","url":null,"abstract":"<p><p>High wall shear stress (HWSS) contributes to intracranial aneurysm (IA) development. However, the underlying molecular mechanisms remain unclear, in part due to the lack of robust animal models that develop IAs in a HWSS-dependent manner. The current study established a new experimental IA model in mice that was utilized to determine HWSS-triggered downstream mechanisms. By a strategic combination of HWSS and low dose elastase, IAs were induced with a high penetrance in hypertensive mice. In contrast, no IAs were observed in control groups where HWSS was absent, suggesting that our new IA model is HWSS-dependent. IA outcomes were assessed by neuroscores that correlate with IA rupture events. Pathological analyses confirmed these experimental IAs resemble those found in humans. Interestingly, HWSS alone promotes the turnover of collagen IV, a major basement membrane component underneath the endothelium, and the formation of endothelial podosomes, subcellular organelles that are known to degrade extracellular matrix proteins. These induced podosomes are functional as they degrade collagen-based substrates locally in the endothelium. These data suggest that this new murine model develops IAs in a HWSS-dependent manner and highlights the contribution of endothelial cells to the early phase of IA. With this model, podosome formation and function was identified as a novel endothelial phenotype triggered by HWSS, which provides new insight into IA pathogenesis.</p>","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astroglial CD38 impairs hippocampal synaptic plasticity after global cerebral ischemia.","authors":"Amelia M Burch, Ami Haas, James E Orfila, Erika Tiemeier, Cassidy De Anda Gamboa, Nicholas Chalmers, Nidia Quillinan, Paco S Herson","doi":"10.3389/fstro.2024.1423887","DOIUrl":"10.3389/fstro.2024.1423887","url":null,"abstract":"<p><p>Cardiac arrest-induced global cerebral ischemia (GCI) results in profound cognitive impairment in survivors. Our prior work demonstrated persistent disruption of long-term potentiation (LTP) in hippocampal CA1 neurons, correlating with learning and memory deficits in a rodent model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Delayed inhibition of the Ca²⁺-permeable TRPM2 ion channel restored LTP post-CA/CPR, yet the mechanisms upstream of TRPM2 activation remain elusive. This study investigates CD38 as a potential regulator of TRPM2, highlighting a novel target to reverse hippocampal synaptic plasticity deficits after ischemia. We observe elevated levels of CD38 in activated astrocytes in the CA1 region of the hippocampus 7 days following CA/CPR in both male and female mice. Delayed inhibition of CD38 reverses hippocampal synaptic plasticity impairments at subacute timepoints after CA/CPR, phenocopying TRPM2 restoration of LTP. Our previous findings demonstrated that TRPM2 inhibition reverses the CA/CPR-induced enhancement of GABA_A receptor (GABA_AR) clustering, which contribute to ongoing LTP deficits. We, therefore, assessed the effect of CD38 on GABAergic inhibitory potentiation and find that inhibition of CD38 reverses GABA_AR clustering in a TRPM2-dependent manner. In this study, we identify astroglial CD38 as a potential target and upstream regulator of the TRPM2 channel, offering a promising approach to restore hippocampal synaptic plasticity impairments following GCI through modulation of GABAergic signaling.</p>","PeriodicalId":73108,"journal":{"name":"Frontiers in stroke","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}