Pub Date : 2024-04-19DOI: 10.1177/0271678x241248502
Joseph V Moxon, Cornea Pretorius, Alexandra F Trollope, Parul Mittal, Manuela Klingler-Hoffmann, Peter Hoffmann, Jonathan Golledge
Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.
{"title":"A systematic review and in silico analysis of studies investigating the ischaemic penumbra proteome in animal models of experimental stroke","authors":"Joseph V Moxon, Cornea Pretorius, Alexandra F Trollope, Parul Mittal, Manuela Klingler-Hoffmann, Peter Hoffmann, Jonathan Golledge","doi":"10.1177/0271678x241248502","DOIUrl":"https://doi.org/10.1177/0271678x241248502","url":null,"abstract":"Ischaemic stroke results in the formation of a cerebral infarction bordered by an ischaemic penumbra. Characterising the proteins within the ischaemic penumbra may identify neuro-protective targets and novel circulating markers to improve patient care. This review assessed data from studies using proteomic platforms to compare ischaemic penumbra tissues to controls following experimental stroke in animal models. Proteins reported to differ significantly between penumbra and control tissues were analysed in silico to identify protein-protein interactions and over-represented pathways. Sixteen studies using rat (n = 12), mouse (n = 2) or primate (n = 2) models were included. Heterogeneity in the design of the studies and definition of the penumbra were observed. Analyses showed high abundance of p53 in the penumbra within 24 hours of permanent ischaemic stroke and was implicated in driving apoptosis, cell cycle progression, and ATM- MAPK- and p53- signalling. Between 1 and 7 days after stroke there were changes in the abundance of proteins involved in the complement and coagulation pathways. Favourable recovery 1 month after stroke was associated with an increase in the abundance of proteins involved in wound healing. Poor recovery was associated with increases in prostaglandin signalling. Findings suggest that p53 may be a target for novel therapeutics for ischaemic stroke.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628685","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}
Pub Date : 2024-04-19DOI: 10.1177/0271678x241230188
Saiyue Deng, Yusi Hu, Simiao Chen, Yang Xue, Di Yao, Qian Sun, Maiken Nedergaard, Wei Wang, Fengfei Ding
Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.
{"title":"Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice","authors":"Saiyue Deng, Yusi Hu, Simiao Chen, Yang Xue, Di Yao, Qian Sun, Maiken Nedergaard, Wei Wang, Fengfei Ding","doi":"10.1177/0271678x241230188","DOIUrl":"https://doi.org/10.1177/0271678x241230188","url":null,"abstract":"Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and that patients with chronically poor sleep undergo an accelerated cognitive decline. Indeed, a single-night of sleep deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how chronic sleep disturbances in isolation from an underlying neurological disease may affect the glymphatic system. Clearance of brain interstitial waste by the glymphatic system occurs primarily during sleep, driven by multiple oscillators including arterial pulsatility, and vasomotion. Herein, we induced sleep fragmentation in young wildtype mice and assessed the effects on glymphatic activity and cognitive functions. Chronic sleep fragmentation reduced glymphatic function and impaired cognitive functions in healthy mice. A mechanistic analysis showed that the chronic sleep fragmentation suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results of this study document that chronic sleep fragmentation suppresses brain metabolite clearance and impairs cognition, even in the absence of disease.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628640","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}
Pub Date : 2024-04-18DOI: 10.1177/0271678x241235878
Joel S Burma, Marc-Antoine Roy, Courtney M Kennedy, Lawrence Labrecque, Patrice Brassard, Jonathan D Smirl
Numerous driven techniques have been utilized to assess dynamic cerebral autoregulation (dCA) in healthy and clinical populations. The current review aimed to amalgamate this literature and provide recommendations to create greater standardization for future research. The PubMed database was searched with inclusion criteria consisting of original research articles using driven dCA assessments in humans. Risk of bias were completed using Scottish Intercollegiate Guidelines Network and Methodological Index for Non-Randomized Studies. Meta-analyses were conducted for coherence, phase, and gain metrics at 0.05 and 0.10 Hz using deep-breathing, oscillatory lower body negative pressure (OLBNP), sit-to-stand maneuvers, and squat-stand maneuvers. A total of 113 studies were included, with 40 of these incorporating clinical populations. A total of 4126 participants were identified, with younger adults (18–40 years) being the most studied population. The most common techniques were squat-stands (n = 43), deep-breathing (n = 25), OLBNP (n = 20), and sit-to-stands (n = 16). Pooled coherence point estimates were: OLBNP 0.70 (95%CI:0.59–0.82), sit-to-stands 0.87 (95%CI:0.79–0.95), and squat-stands 0.98 (95%CI:0.98–0.99) at 0.05 Hz; and deep-breathing 0.90 (95%CI:0.81–0.99); OLBNP 0.67 (95%CI:0.44–0.90); and squat-stands 0.99 (95%CI:0.99–0.99) at 0.10 Hz. This review summarizes clinical findings, discusses the pros/cons of the 11 unique driven techniques included, and provides recommendations for future investigations into the unique physiological intricacies of dCA.
{"title":"A systematic review, meta-analysis, and meta-regression amalgamating the driven approaches used to quantify dynamic cerebral autoregulation","authors":"Joel S Burma, Marc-Antoine Roy, Courtney M Kennedy, Lawrence Labrecque, Patrice Brassard, Jonathan D Smirl","doi":"10.1177/0271678x241235878","DOIUrl":"https://doi.org/10.1177/0271678x241235878","url":null,"abstract":"Numerous driven techniques have been utilized to assess dynamic cerebral autoregulation (dCA) in healthy and clinical populations. The current review aimed to amalgamate this literature and provide recommendations to create greater standardization for future research. The PubMed database was searched with inclusion criteria consisting of original research articles using driven dCA assessments in humans. Risk of bias were completed using Scottish Intercollegiate Guidelines Network and Methodological Index for Non-Randomized Studies. Meta-analyses were conducted for coherence, phase, and gain metrics at 0.05 and 0.10 Hz using deep-breathing, oscillatory lower body negative pressure (OLBNP), sit-to-stand maneuvers, and squat-stand maneuvers. A total of 113 studies were included, with 40 of these incorporating clinical populations. A total of 4126 participants were identified, with younger adults (18–40 years) being the most studied population. The most common techniques were squat-stands (n = 43), deep-breathing (n = 25), OLBNP (n = 20), and sit-to-stands (n = 16). Pooled coherence point estimates were: OLBNP 0.70 (95%CI:0.59–0.82), sit-to-stands 0.87 (95%CI:0.79–0.95), and squat-stands 0.98 (95%CI:0.98–0.99) at 0.05 Hz; and deep-breathing 0.90 (95%CI:0.81–0.99); OLBNP 0.67 (95%CI:0.44–0.90); and squat-stands 0.99 (95%CI:0.99–0.99) at 0.10 Hz. This review summarizes clinical findings, discusses the pros/cons of the 11 unique driven techniques included, and provides recommendations for future investigations into the unique physiological intricacies of dCA.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628530","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}
Pub Date : 2024-04-17DOI: 10.1177/0271678x241245633
Yue Cheng, Yueman Zhang, Peiying Li
Cell therapy and regenerative medicine have made remarkable progress in treating neurodegenerative disorders. Induced pluripotent stem cells (iPSCs) offer a promising source for cell replacement therapies, but their practical application faces challenges due to poor survival and integration after transplantation. Park et al. propose a novel therapeutic strategy involving the co-transplantation of regulatory T cells (Tregs) and iPSC-derived dopamine neurons. This combined approach enhances the survival of transplanted cells and protects against neuroinflammation-induced damage. In PD animal models, the co-transplantation approach significantly suppressed the host immune response, resulting in improved behavioral recovery. Additionally, Tregs demonstrate acute neuroprotection and contribute to delayed neuro-restoration in ischemic stroke. This combined approach of cell therapy with immunomodulation offers a promising avenue for advancing our understanding of neurological diseases and promoting the development of novel treatments.
细胞疗法和再生医学在治疗神经退行性疾病方面取得了显著进展。诱导多能干细胞（iPSCs）为细胞替代疗法提供了一个前景广阔的来源，但由于移植后存活率和整合率低，其实际应用面临挑战。Park 等人提出了一种新的治疗策略，涉及调节性 T 细胞（Tregs）和 iPSC 衍生的多巴胺神经元的联合移植。这种联合方法可提高移植细胞的存活率，并防止神经炎症引起的损伤。在帕金森病动物模型中，联合移植方法显著抑制了宿主免疫反应，从而改善了行为恢复。此外，Tregs 还具有急性神经保护作用，并有助于缺血性中风的延迟神经恢复。这种将细胞疗法与免疫调节相结合的方法为增进我们对神经系统疾病的了解和促进新型疗法的开发提供了一条前景广阔的途径。
{"title":"Co-transplantation of autologous treg cells: A groundbreaking cell therapy for brain diseases","authors":"Yue Cheng, Yueman Zhang, Peiying Li","doi":"10.1177/0271678x241245633","DOIUrl":"https://doi.org/10.1177/0271678x241245633","url":null,"abstract":"Cell therapy and regenerative medicine have made remarkable progress in treating neurodegenerative disorders. Induced pluripotent stem cells (iPSCs) offer a promising source for cell replacement therapies, but their practical application faces challenges due to poor survival and integration after transplantation. Park et al. propose a novel therapeutic strategy involving the co-transplantation of regulatory T cells (Tregs) and iPSC-derived dopamine neurons. This combined approach enhances the survival of transplanted cells and protects against neuroinflammation-induced damage. In PD animal models, the co-transplantation approach significantly suppressed the host immune response, resulting in improved behavioral recovery. Additionally, Tregs demonstrate acute neuroprotection and contribute to delayed neuro-restoration in ischemic stroke. This combined approach of cell therapy with immunomodulation offers a promising avenue for advancing our understanding of neurological diseases and promoting the development of novel treatments.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611184","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}
Pub Date : 2024-04-13DOI: 10.1177/0271678x241248228
Michael M Tymko, Audrey Drapeau, Maria Augusta Vieira-Coelho, Lawrence Labrecque, Sarah Imhoff, Geoff B Coombs, Stephan Langevin, Marc Fortin, Nathalie Châteauvert, Philip N Ainslie, Patrice Brassard
The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein. Heart rate was recorded via electrocardiogram and blood pressure was monitored using the right radial artery. Total NA spillover increased during HG (P = 0.049), PECO (P = 0.006), and moderate cycling exercise (P = 0.03) compared to rest. Cerebral NA spillover remained unchanged during isometric HG exercise (P = 0.36), PECO after the isometric HG exercise (P = 0.45), and during moderate cycling exercise (P = 0.94) compared to rest. These results indicate that transient increases in blood pressure during acute exercise involving both small and large muscle mass do not engage cerebral SNA in healthy humans. Our findings suggest that cerebral SNA may be non-obligatory for exercise-related cerebrovascular adjustments.
{"title":"Acute isometric and dynamic exercise do not alter cerebral sympathetic nerve activity in healthy humans","authors":"Michael M Tymko, Audrey Drapeau, Maria Augusta Vieira-Coelho, Lawrence Labrecque, Sarah Imhoff, Geoff B Coombs, Stephan Langevin, Marc Fortin, Nathalie Châteauvert, Philip N Ainslie, Patrice Brassard","doi":"10.1177/0271678x241248228","DOIUrl":"https://doi.org/10.1177/0271678x241248228","url":null,"abstract":"The impact of physiological stressors on cerebral sympathetic nervous activity (SNA) remains controversial. We hypothesized that cerebral noradrenaline (NA) spillover, an index of cerebral SNA, would not change during both submaximal isometric handgrip (HG) exercise followed by a post-exercise circulatory occlusion (PECO), and supine dynamic cycling exercise. Twelve healthy participants (5 females) underwent simultaneous blood sampling from the right radial artery and right internal jugular vein. Right internal jugular vein blood flow was measured using Duplex ultrasound, and tritiated NA was infused through the participants' right superficial forearm vein. Heart rate was recorded via electrocardiogram and blood pressure was monitored using the right radial artery. Total NA spillover increased during HG (P = 0.049), PECO (P = 0.006), and moderate cycling exercise (P = 0.03) compared to rest. Cerebral NA spillover remained unchanged during isometric HG exercise (P = 0.36), PECO after the isometric HG exercise (P = 0.45), and during moderate cycling exercise (P = 0.94) compared to rest. These results indicate that transient increases in blood pressure during acute exercise involving both small and large muscle mass do not engage cerebral SNA in healthy humans. Our findings suggest that cerebral SNA may be non-obligatory for exercise-related cerebrovascular adjustments.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568727","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}
Pub Date : 2024-04-13DOI: 10.1177/0271678x241247633
Lawrence Labrecque, Marc-Antoine Roy, Shahrzad Soleimani Dehnavi, Mahmoudreza Taghizadeh, Jonathan D Smirl, Patrice Brassard
A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAvT/ΔMAPT) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to −90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAvT/ΔMAPT during OLBNP-induced MAP increases (INC) (ΔMCAvT/[Formula: see text]) and decreases (DEC) (ΔMCAvT/[Formula: see text]). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAvT/ΔMAPT between INC and DEC at 0.05 Hz. ΔMCAvT/[Formula: see text] (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s−1/mmHg; p = 0.0076) was lower than ΔMCAvT/[Formula: see text] at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.
{"title":"Directional sensitivity of the cerebral pressure-flow relationship during forced oscillations induced by oscillatory lower body negative pressure","authors":"Lawrence Labrecque, Marc-Antoine Roy, Shahrzad Soleimani Dehnavi, Mahmoudreza Taghizadeh, Jonathan D Smirl, Patrice Brassard","doi":"10.1177/0271678x241247633","DOIUrl":"https://doi.org/10.1177/0271678x241247633","url":null,"abstract":"A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAv<jats:sub>T</jats:sub>/ΔMAP<jats:sub>T</jats:sub>) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to −90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAv<jats:sub>T</jats:sub>/ΔMAP<jats:sub>T</jats:sub> during OLBNP-induced MAP increases (INC) (ΔMCAv<jats:sub>T</jats:sub>/[Formula: see text]) and decreases (DEC) (ΔMCAv<jats:sub>T</jats:sub>/[Formula: see text]). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAv<jats:sub>T</jats:sub>/ΔMAP<jats:sub>T</jats:sub> between INC and DEC at 0.05 Hz. ΔMCAv<jats:sub>T</jats:sub>/[Formula: see text] (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s<jats:sup>−1</jats:sup>/mmHg; p = 0.0076) was lower than ΔMCAv<jats:sub>T</jats:sub>/[Formula: see text] at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568817","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}
The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage. They are now viewed as integral parts of brain metabolism. In addition to their energetic role, experimental evidence also supports their neuroprotective properties after acute brain injury, regulating in particular intracranial pressure control, decreasing ischemic volume, and leading to an improvement in cognitive functions as well as survival. In this review, we present preclinical and clinical evidence exploring the mechanisms underlying their neuroprotective effects and identify research priorities for promoting lactate and ketone bodies use in brain injury.
{"title":"Neuroprotective effects of lactate and ketone bodies in acute brain injury","authors":"Guillaume Plourde, Hélène Roumes, Laurent Suissa, Lorenz Hirt, Émilie Doche, Luc Pellerin, Anne-Karine Bouzier-Sore, Hervé Quintard","doi":"10.1177/0271678x241245486","DOIUrl":"https://doi.org/10.1177/0271678x241245486","url":null,"abstract":"The goal of neurocritical care is to prevent and reverse the pathologic cascades of secondary brain injury by optimizing cerebral blood flow, oxygen supply and substrate delivery. While glucose is an essential energetic substrate for the brain, we frequently observe a strong decrease in glucose delivery and/or a glucose metabolic dysregulation following acute brain injury. In parallel, during the last decades, lactate and ketone bodies have been identified as potential alternative fuels to provide energy to the brain, both under physiological conditions and in case of glucose shortage. They are now viewed as integral parts of brain metabolism. In addition to their energetic role, experimental evidence also supports their neuroprotective properties after acute brain injury, regulating in particular intracranial pressure control, decreasing ischemic volume, and leading to an improvement in cognitive functions as well as survival. In this review, we present preclinical and clinical evidence exploring the mechanisms underlying their neuroprotective effects and identify research priorities for promoting lactate and ketone bodies use in brain injury.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569026","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}
Pub Date : 2024-04-11DOI: 10.1177/0271678x241245488
Jordan D Bird, David B MacLeod, Donald E Griesdale, Mypinder S Sekhon, Ryan L Hoiland
The near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx) has become popularized for non-invasive neuromonitoring of cerebrovascular function in post-cardiac arrest patients with hypoxic-ischemic brain injury (HIBI). We provide commentary on the physiologic underpinnings and assumptions of NIRS and the COx, potential confounds in the context of HIBI, and the implications for the assessment of cerebral autoregulation.
{"title":"Shining a light on cerebral autoregulation: Are we anywhere near the truth?","authors":"Jordan D Bird, David B MacLeod, Donald E Griesdale, Mypinder S Sekhon, Ryan L Hoiland","doi":"10.1177/0271678x241245488","DOIUrl":"https://doi.org/10.1177/0271678x241245488","url":null,"abstract":"The near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx) has become popularized for non-invasive neuromonitoring of cerebrovascular function in post-cardiac arrest patients with hypoxic-ischemic brain injury (HIBI). We provide commentary on the physiologic underpinnings and assumptions of NIRS and the COx, potential confounds in the context of HIBI, and the implications for the assessment of cerebral autoregulation.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568919","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}
As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis. After adjusting for confounding factors, patients in tertile 3 exhibited an increased risk of poor functional outcome and mortality [odds ratio (OR), 2.656 (95% CI: 1.443–4.889); OR, 7.586 (95% CI: 2.102–27.375)]. A systematic search of PubMed, EMBASE and Cochrane Library was performed. Our meta-analysis revealed that LVEF < 40% was significantly associated with poor functional outcome [OR 1.94 (95% CI: 1.08–3.50)], mortality [OR 3.69 (95% CI: 1.22–11.11)], as well as LVEF < 55% [OR 1.68 (95% CI: 1.22–2.32); 2.27 (95% CI: 1.30–3.96)], respectively. A decreased LVEF could predict an inferior prognosis for AIS; therefore, it could aid in clinical decision-making in this patient population.
{"title":"Prediction of trends in unfavorable prognosis in patients with acute ischemic stroke according to low left ventricular ejection fraction levels","authors":"Dehao Yang, Jingyu Hu, Minyue Zhang, Yiqun Chen, Haobo Xie, Yining Jin, Zerui Jiang, Jiaqi Huang, Kun Li, Jiexi Huang, Yanchu Wang, Yiyun Weng, Guangyong Chen","doi":"10.1177/0271678x241247020","DOIUrl":"https://doi.org/10.1177/0271678x241247020","url":null,"abstract":"As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis. After adjusting for confounding factors, patients in tertile 3 exhibited an increased risk of poor functional outcome and mortality [odds ratio (OR), 2.656 (95% CI: 1.443–4.889); OR, 7.586 (95% CI: 2.102–27.375)]. A systematic search of PubMed, EMBASE and Cochrane Library was performed. Our meta-analysis revealed that LVEF < 40% was significantly associated with poor functional outcome [OR 1.94 (95% CI: 1.08–3.50)], mortality [OR 3.69 (95% CI: 1.22–11.11)], as well as LVEF < 55% [OR 1.68 (95% CI: 1.22–2.32); 2.27 (95% CI: 1.30–3.96)], respectively. A decreased LVEF could predict an inferior prognosis for AIS; therefore, it could aid in clinical decision-making in this patient population.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568857","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}
Pub Date : 2024-04-05DOI: 10.1177/0271678x241241895
Harm Jan van der Horn, Andrei A Vakhtin, Kayla Julio, Stephanie Nitschke, Nicholas Shaff, Andrew B Dodd, Erik Erhardt, John P Phillips, Sarah Pirio Richardson, Amanda Deligtisch, Melanie Stewart, Gerson Suarez Cedeno, Sanne K Meles, Andrew R Mayer, Sephira G Ryman
A mounting body of research points to cerebrovascular dysfunction as a fundamental element in the pathophysiology of Parkinson’s disease (PD). In the current feasibility study, blood-oxygen-level-dependent (BOLD) MRI was used to measure cerebrovascular reactivity (CVR) in response to hypercapnia in 26 PD patients and 16 healthy controls (HC), and aimed to find a multivariate pattern specific to PD. Whole-brain maps of CVR amplitude (i.e., magnitude of response to CO2) and latency (i.e., time to reach maximum amplitude) were computed, which were further analyzed using scaled sub-profile model principal component analysis (SSM-PCA) with leave-one-out cross-validation. A meaningful pattern based on CVR latency was identified, which was named the PD CVR pattern (PD-CVRP). This pattern was characterized by relatively increased latency in basal ganglia, sensorimotor cortex, supplementary motor area, thalamus and visual cortex, as well as decreased latency in the cerebral white matter, relative to HC. There were no significant associations with clinical measures, though sample size may have limited our ability to detect significant associations. In summary, the PD-CVRP highlights the importance of cerebrovascular dysfunction in PD, and may be a potential biomarker for future clinical research and practice.
{"title":"Parkinson’s disease cerebrovascular reactivity pattern: A feasibility study","authors":"Harm Jan van der Horn, Andrei A Vakhtin, Kayla Julio, Stephanie Nitschke, Nicholas Shaff, Andrew B Dodd, Erik Erhardt, John P Phillips, Sarah Pirio Richardson, Amanda Deligtisch, Melanie Stewart, Gerson Suarez Cedeno, Sanne K Meles, Andrew R Mayer, Sephira G Ryman","doi":"10.1177/0271678x241241895","DOIUrl":"https://doi.org/10.1177/0271678x241241895","url":null,"abstract":"A mounting body of research points to cerebrovascular dysfunction as a fundamental element in the pathophysiology of Parkinson’s disease (PD). In the current feasibility study, blood-oxygen-level-dependent (BOLD) MRI was used to measure cerebrovascular reactivity (CVR) in response to hypercapnia in 26 PD patients and 16 healthy controls (HC), and aimed to find a multivariate pattern specific to PD. Whole-brain maps of CVR amplitude (i.e., magnitude of response to CO<jats:sub>2</jats:sub>) and latency (i.e., time to reach maximum amplitude) were computed, which were further analyzed using scaled sub-profile model principal component analysis (SSM-PCA) with leave-one-out cross-validation. A meaningful pattern based on CVR latency was identified, which was named the PD CVR pattern (PD-CVRP). This pattern was characterized by relatively increased latency in basal ganglia, sensorimotor cortex, supplementary motor area, thalamus and visual cortex, as well as decreased latency in the cerebral white matter, relative to HC. There were no significant associations with clinical measures, though sample size may have limited our ability to detect significant associations. In summary, the PD-CVRP highlights the importance of cerebrovascular dysfunction in PD, and may be a potential biomarker for future clinical research and practice.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140569295","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}
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