Pub Date : 2024-09-09DOI: 10.1177/0271678X241281485
Ingrid Magnet, Alexandra-Maria Stommel, Christoph Schriefl, Matthias Mueller, Michael Poppe, Juergen Grafeneder, Christoph Testori, Andreas Janata, Andreas Schober, Daniel Grassmann, Wilhelm Behringer, Wolfgang Weihs, Michael Holzer, Sandra Hoegler, Florian Ettl
Extracorporeal cardiopulmonary resuscitation (ECPR) facilitates resuscitation with immediate and precise temperature control. This study aimed to determine the optimal reperfusion temperature to minimize neurological damage after ventricular fibrillation cardiac arrest (VFCA). Twenty-four rats were randomized (n = 8 per group) to normothermia (NT = 37°C), mild hypothermia (MH = 33°C) or moderate hypothermia (MOD = 27°C). The rats were subjected to 10 minutes of VFCA, before 15 minutes of ECPR at their respective target temperature. After ECPR weaning, rats in the MOD group were rapidly rewarmed to 33°C, and temperature maintained at 33°C (MH/MOD) or 37°C (NT) for 12 hours before slow rewarming to normothermia (MH/MOD). The primary outcome was 30-day survival with overall performance category (OPC) 1 or 2 (1 = normal, 2 = slight disability, 3 = severe disability, 4 = comatose, 5 = dead). Secondary outcomes included awakening rate (OPC ≤ 3) and neurological deficit score (NDS, from 0 = normal to 100 = brain dead). The survival rate did not differ between reperfusion temperatures (NT = 25%, MH = 63%, MOD = 38%, p = 0.301). MH had the lowest NDS (NT = 4[IQR 3-4], MH = 2[1-2], MOD = 5[3-5], p = 0.044) and highest awakening rate (NT = 25%, MH = 88%, MOD = 75%, p = 0.024). In conclusion, ECPR with 33°C reperfusion did not statistically significantly improve survival after VFCA when compared with 37°C or 27°C reperfusion but was neuroprotective as measured by awakening rate and neurological function.
{"title":"Neuroprotection with hypothermic reperfusion and extracorporeal cardiopulmonary resuscitation - A randomized controlled animal trial of prolonged ventricular fibrillation cardiac arrest in rats.","authors":"Ingrid Magnet, Alexandra-Maria Stommel, Christoph Schriefl, Matthias Mueller, Michael Poppe, Juergen Grafeneder, Christoph Testori, Andreas Janata, Andreas Schober, Daniel Grassmann, Wilhelm Behringer, Wolfgang Weihs, Michael Holzer, Sandra Hoegler, Florian Ettl","doi":"10.1177/0271678X241281485","DOIUrl":"10.1177/0271678X241281485","url":null,"abstract":"<p><p>Extracorporeal cardiopulmonary resuscitation (ECPR) facilitates resuscitation with immediate and precise temperature control. This study aimed to determine the optimal reperfusion temperature to minimize neurological damage after ventricular fibrillation cardiac arrest (VFCA). Twenty-four rats were randomized (n = 8 per group) to normothermia (NT = 37°C), mild hypothermia (MH = 33°C) or moderate hypothermia (MOD = 27°C). The rats were subjected to 10 minutes of VFCA, before 15 minutes of ECPR at their respective target temperature. After ECPR weaning, rats in the MOD group were rapidly rewarmed to 33°C, and temperature maintained at 33°C (MH/MOD) or 37°C (NT) for 12 hours before slow rewarming to normothermia (MH/MOD). The primary outcome was 30-day survival with overall performance category (OPC) 1 or 2 (1 = normal, 2 = slight disability, 3 = severe disability, 4 = comatose, 5 = dead). Secondary outcomes included awakening rate (OPC ≤ 3) and neurological deficit score (NDS, from 0 = normal to 100 = brain dead). The survival rate did not differ between reperfusion temperatures (NT = 25%, MH = 63%, MOD = 38%, p = 0.301). MH had the lowest NDS (NT = 4[IQR 3-4], MH = 2[1-2], MOD = 5[3-5], p = 0.044) and highest awakening rate (NT = 25%, MH = 88%, MOD = 75%, p = 0.024). In conclusion, ECPR with 33°C reperfusion did not statistically significantly improve survival after VFCA when compared with 37°C or 27°C reperfusion but was neuroprotective as measured by awakening rate and neurological function.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241281485"},"PeriodicalIF":4.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100β, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100β), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100β, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.
外周炎症的动态发展是否会加重脑损伤并导致接受静脉溶栓(IVT)的脑卒中患者预后不佳,目前仍不清楚,需要进一步研究。本研究共纳入了 1034 名接受静脉溶栓治疗的急性缺血性脑卒中患者。研究记录了血清白细胞的变化(从基线到静脉溶栓后24小时是否增加)、美国国立卫生研究院卒中量表(NIHSS)、梗死体积、早期神经功能恶化(END)、3个月时的不良预后(改良Rankin量表[mRS]评分≥3)和死亡率。测量血清脑损伤生物标志物,包括胶质纤维酸性蛋白(GFAP)、泛素 c 端水解酶 L1(UCH-L1)、S100β、神经元特异性烯醇化酶(NSE),以反映脑损伤的程度。我们发现,血清白细胞增高的患者脑损伤生物标志物(GFAP、UCH-L1 和 S100β)升高,梗死体积增大,24 h NIHSS 增高,END 比例增高,预后不良,死亡率增高。此外,血清白细胞的增加与梗死容积、24 h NIHSS、END、3 个月时的不良预后以及血清 UCH-L1、S100β 和 NSE 水平均有独立相关性。这些结果表明,血清白细胞的增加预示着严重的脑损伤,可用于预测接受 IVT 的缺血性脑卒中患者的预后。
{"title":"Increased peripheral leukocyte aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis: A study based on clinical evidence.","authors":"Ke-Jia Zhang, Yang Qu, Reziya Abuduxukuer, Peng Zhang, Yu Zhang, Jian-Hua Gao, Xian-Kun Zhang, Xiao-Dong Liu, Chun-Ying Li, Guang-Cai Li, Jun-Min Wang, Hui-Min Jin, Ying He, Li-Gang Jiang, Liang Liu, Yongfei Jiang, Rui-Hong Teng, Yan Jia, Bai-Jing Zhang, Zhi-Bo Chen, Yingbin Qi, Xiu-Ping Liu, Song Li, Thanh N Nguyen, Yi Yang, Zhen-Ni Guo","doi":"10.1177/0271678X241281020","DOIUrl":"10.1177/0271678X241281020","url":null,"abstract":"<p><p>Whether the dynamic development of peripheral inflammation aggravates brain injury and leads to poor outcome in stroke patients receiving intravenous thrombolysis (IVT), remains unclear and warrants further study. In this study, total of 1034 patients with acute ischemic stroke who underwent IVT were enrolled. Serum leukocyte variation (whether increase from baseline to 24 h after IVT), National Institutes of Health Stroke Scale (NIHSS), infarct volume, early neurologic deterioration (END), the unfavorable outcome at 3-month (modified Rankin Scale [mRS] score ≥3) and mortality were recorded. Serum brain injury biomarkers, including Glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100<i>β</i>, neuron-specific enolase (NSE), were measured to reflect the extent of brain injury. We found that patients with increased serum leukocytes had elevated brain injury biomarkers (GFAP, UCH-L1, and S100<i>β</i>), larger infarct volume, higher 24 h NIHSS, higher proportion of END, unfavorable outcome and mortality. Furthermore, an increase in serum leukocytes was independently associated with infarct volume, 24 h NIHSS, END, and unfavorable outcome at 3 months, and serum UCH-L1, S100<i>β</i>, and NSE levels. These results suggest that an increase in serum leukocytes indicates severe brain injury and may be used to predict the outcome of patients with ischemic stroke who undergo IVT.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241281020"},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-03DOI: 10.1177/0271678X241270420
Nuwan D Nanayakkara, Liesel-Ann Meusel, Nicole D Anderson, J Jean Chen
In this work, we demonstrate a data-driven approach for estimating cerebrovascular reactivity (CVR) amplitude and lag from breathhold (BH) fMRI data alone. Our approach employs a frequency-domain approach that is independent of external recordings. CVR amplitude is estimated from the BOLD frequency spectrum and CVR lag is estimated from the Fourier phase using the global-mean BOLD signal as reference. Unlike referencing to external recordings, these lags are specific to the brain. We demonstrated our method in detecting regional CVR amplitude and lag differences across healthy (CTL), hypertensive (HT) and hypertension-plus-type-2-diabetes (HT + DM) groups of similar ages and sex ratios, with a total N of 49. We found CVR amplitude to be significantly higher in CTL compared to HT + DM, with minimal difference between CTL and HT. Also, voxelwise CVR lag estimated in the Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. CVR lag in HT is significantly shorter than in CTL, with minimal difference between CTL and HT + DM. Our results support the importance of joint CVR amplitude and lag assessments in clinical applications.
{"title":"Estimation of cerebrovascular reactivity amplitude and lag using breath-holding fMRI and the global BOLD signal: Application in diabetes and hypertension.","authors":"Nuwan D Nanayakkara, Liesel-Ann Meusel, Nicole D Anderson, J Jean Chen","doi":"10.1177/0271678X241270420","DOIUrl":"10.1177/0271678X241270420","url":null,"abstract":"<p><p>In this work, we demonstrate a data-driven approach for estimating cerebrovascular reactivity (CVR) amplitude and lag from breathhold (BH) fMRI data alone. Our approach employs a frequency-domain approach that is independent of external recordings. CVR amplitude is estimated from the BOLD frequency spectrum and CVR lag is estimated from the Fourier phase using the global-mean BOLD signal as reference. Unlike referencing to external recordings, these lags are specific to the brain. We demonstrated our method in detecting regional CVR amplitude and lag differences across healthy (CTL), hypertensive (HT) and hypertension-plus-type-2-diabetes (HT + DM) groups of similar ages and sex ratios, with a total <i>N</i> of 49. We found CVR amplitude to be significantly higher in CTL compared to HT + DM, with minimal difference between CTL and HT. Also, voxelwise CVR lag estimated in the Fourier domain is a more sensitive marker of vascular dysfunction than CVR amplitude. CVR lag in HT is significantly shorter than in CTL, with minimal difference between CTL and HT + DM. Our results support the importance of joint CVR amplitude and lag assessments in clinical applications.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"271678X241270420"},"PeriodicalIF":4.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca2+ levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT1B receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.
{"title":"Serotonergic regulation of cortical neurovascular coupling and hemodynamics upon awakening from sleep in mice.","authors":"Akiyo Natsubori, Soojin Kwon, Yoshiko Honda, Takashi Kojima, Akihiro Karashima, Kazuto Masamoto, Makoto Honda","doi":"10.1177/0271678X241238843","DOIUrl":"10.1177/0271678X241238843","url":null,"abstract":"<p><p>Neurovascular coupling (NVC) is the functional hyperemia of the brain responding to local neuronal activity. It is mediated by astrocytes and affected by subcortical ascending pathways in the cortex that convey information, such as sensory stimuli and the animal condition. Here, we investigate the influence of the raphe serotonergic system, a subcortical ascending arousal system in animals, on the modulation of cortical NVC and cerebral blood flow (CBF). Raphe serotonergic neurons were optogenically activated for 30 s, which immediately awakened the mice from non-rapid eye movement sleep. This caused a biphasic cortical hemodynamic change: a transient increase for a few seconds immediately after photostimulation onset, followed by a large progressive decrease during the stimulation period. Serotonergic neuron activation increased intracellular Ca<sup>2+</sup> levels in cortical pyramidal neurons and astrocytes, demonstrating its effect on the NVC components. Pharmacological inhibition of cortical neuronal firing activity and astrocyte metabolic activity had small hypovolemic effects on serotonin-induced biphasic CBF changes, while blocking 5-HT<sub>1B</sub> receptors expressed primarily in cerebral vasculature attenuated the decreasing CBF phase. This suggests that serotonergic neuron activation leading to animal awakening could allow the NVC to exert a hyperemic function during a biphasic CBF response, with a predominant decrease in the cortex.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1591-1607"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.
{"title":"The effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy.","authors":"Mengmeng Wang, Changwei Guo, Jie Yang, Jing Li, Jinrong Hu, Zhouzhou Peng, Meng Guo, Lingyu Zhang, Fengli Li, Qingwu Yang, Wenjie Zi, Pengfei Wang","doi":"10.1177/0271678X241238033","DOIUrl":"10.1177/0271678X241238033","url":null,"abstract":"<p><p>The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; <i>p = </i>0.016) favoring HUK. The incidence of sICH (2.0% <i>vs.</i> 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; <i>p = </i>0.007) and mortality (11.3% <i>vs.</i>18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; <i>p = </i>0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1565-1576"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-03-20DOI: 10.1177/0271678X241238935
Lena Schmitzer, Stephan Kaczmarz, Jens Göttler, Gabriel Hoffmann, Michael Kallmayer, Hans-Henning Eckstein, Dennis Martin Hedderich, Jan Kufer, Claus Zimmer, Christine Preibisch, Fahmeed Hyder, Nico Sollmann
Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.
{"title":"Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis.","authors":"Lena Schmitzer, Stephan Kaczmarz, Jens Göttler, Gabriel Hoffmann, Michael Kallmayer, Hans-Henning Eckstein, Dennis Martin Hedderich, Jan Kufer, Claus Zimmer, Christine Preibisch, Fahmeed Hyder, Nico Sollmann","doi":"10.1177/0271678X241238935","DOIUrl":"10.1177/0271678X241238935","url":null,"abstract":"<p><p>Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1629-1642"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-03-21DOI: 10.1177/0271678X241240590
Miao Sun, Xin Huang, Xuelei Ruan, Xiuli Shang, Mengyang Zhang, Libo Liu, Ping Wang, Ping An, Yang Lin, Jin Yang, Yixue Xue
Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.
{"title":"Cpeb4-mediated Dclk2 promotes neuronal pyroptosis induced by chronic cerebral ischemia through phosphorylation of Ehf.","authors":"Miao Sun, Xin Huang, Xuelei Ruan, Xiuli Shang, Mengyang Zhang, Libo Liu, Ping Wang, Ping An, Yang Lin, Jin Yang, Yixue Xue","doi":"10.1177/0271678X241240590","DOIUrl":"10.1177/0271678X241240590","url":null,"abstract":"<p><p>Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1655-1673"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-21DOI: 10.1177/0271678X241264086
Silin Wu, Xuefang Sophie Ren, Yejie Shi
The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.
{"title":"Early and enduring: Targeting the endothelium for blood-brain barrier protection.","authors":"Silin Wu, Xuefang Sophie Ren, Yejie Shi","doi":"10.1177/0271678X241264086","DOIUrl":"10.1177/0271678X241264086","url":null,"abstract":"<p><p>The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1674-1676"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-03-14DOI: 10.1177/0271678X241239783
Sungtak Hong, Jyoti Singh Tomar, Jun Shen
A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson's spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically eliminated to facilitate the determination of any metabolic link between glutamate and N-acetylaspartate in the human brain using in vivo magnetic resonance spectroscopy. In both occipital and medial prefrontal cortices of healthy individuals, correlations between glutamate and N-acetylaspartate were found to be insignificant. Our results do not lend support to a recent hypothesis that N-acetylaspartate serves as a significant reservoir for the rapid replenishment of glutamate during signaling or stress.
{"title":"Metabolic coupling between glutamate and N-acetylaspartate in the human brain.","authors":"Sungtak Hong, Jyoti Singh Tomar, Jun Shen","doi":"10.1177/0271678X241239783","DOIUrl":"10.1177/0271678X241239783","url":null,"abstract":"<p><p>A metabolic coupling between glutamate and N-acetylaspartate measured by in vivo magnetic resonance spectroscopy has been recently reported in the literature with inconsistent findings. In this study, confounders originating from Pearson's spurious correlation of ratios and spectral correlation due to overlapping magnetic resonance spectroscopy signals of glutamate and N-acetylaspartate were practically eliminated to facilitate the determination of any metabolic link between glutamate and N-acetylaspartate in the human brain using in vivo magnetic resonance spectroscopy. In both occipital and medial prefrontal cortices of healthy individuals, correlations between glutamate and N-acetylaspartate were found to be insignificant. Our results do not lend support to a recent hypothesis that N-acetylaspartate serves as a significant reservoir for the rapid replenishment of glutamate during signaling or stress.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1608-1617"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Preterm birth is associated with cerebrovascular development disruption and can induce white matter injuries (WMI). Transfontanellar ultrasound Doppler is the most widely used clinical imaging technique to monitor neonatal cerebral vascularisation and haemodynamics based on vascular indexes such as the resistivity index (RI); however, it has poor predictive value for brain damage. Indeed, these RI measurements are currently limited to large vessels, leading to a very limited probing of the brain's vascularisation, which may hinder prognosis. Here we show that ultrafast Doppler imaging (UfD) enables simultaneous quantification, in the whole field of view, of the local RI and vessel diameter, even in small vessels. Combining both pieces of information, we defined two new comprehensive resistivity parameters of the vascular trees. First, we showed that our technique is more sensitive in the early characterisation of the RI modifications between term and preterm neonates and for the first time we could show that the RI depends both on the vessel diameter and vascular territory. We then showed that our parameters can be used for early prediction of WMI. Our results demonstrate the potential of UfD to provide new biomarkers and pave the way for continuous monitoring of neonatal brain resistivity.
早产与脑血管发育障碍有关,并可诱发脑白质损伤(WMI)。根据血管指数(如电阻率指数(RI))监测新生儿脑血管化和血流动力学,经颅骨超声多普勒是最广泛应用的临床成像技术;然而,它对脑损伤的预测价值很低。事实上,这些 RI 测量目前仅限于大血管,导致对脑血管的探测非常有限,这可能会妨碍预后。在这里,我们展示了超快多普勒成像(UfD)能在整个视野中同时量化局部 RI 和血管直径,即使在小血管中也是如此。结合这两项信息,我们定义了血管树的两个新的综合电阻率参数。首先,我们证明了我们的技术在早期鉴定足月和早产新生儿的 RI 变化特征方面更加灵敏,并且首次证明了 RI 同时取决于血管直径和血管区域。随后,我们证明了我们的参数可用于早期预测 WMI。我们的研究结果证明了 UfD 在提供新生物标记物方面的潜力,并为持续监测新生儿脑电阻率铺平了道路。
{"title":"Quantification of brain-wide vascular resistivity via ultrafast Doppler in human neonates helps early detection of white matter injury.","authors":"Flora Faure, Jérôme Baranger, Marianne Alison, Béatrice Boutillier, Alice Frérot, Chung Lim, Grégory Planchette, Mickael Prigent, Mickaël Tanter, Olivier Baud, Valérie Biran, Charlie Demené","doi":"10.1177/0271678X241232197","DOIUrl":"10.1177/0271678X241232197","url":null,"abstract":"<p><p>Preterm birth is associated with cerebrovascular development disruption and can induce white matter injuries (WMI). Transfontanellar ultrasound Doppler is the most widely used clinical imaging technique to monitor neonatal cerebral vascularisation and haemodynamics based on vascular indexes such as the resistivity index (RI); however, it has poor predictive value for brain damage. Indeed, these RI measurements are currently limited to large vessels, leading to a very limited probing of the brain's vascularisation, which may hinder prognosis. Here we show that ultrafast Doppler imaging (UfD) enables simultaneous quantification, in the whole field of view, of the local RI and vessel diameter, even in small vessels. Combining both pieces of information, we defined two new comprehensive resistivity parameters of the vascular trees. First, we showed that our technique is more sensitive in the early characterisation of the RI modifications between term and preterm neonates and for the first time we could show that the RI depends both on the vessel diameter and vascular territory. We then showed that our parameters can be used for early prediction of WMI. Our results demonstrate the potential of UfD to provide new biomarkers and pave the way for continuous monitoring of neonatal brain resistivity.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"1577-1590"},"PeriodicalIF":4.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}