Pub Date : 2020-08-01DOI: 10.1177/0271678X19871253
J. Nawabi, H. Kniep, G. Broocks, T. Faizy, G. Schön, G. Thomalla, J. Fiehler, U. Hanning
Asymptomatic intracerebral hemorrhage (aICH) is a common phenomenon in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (ET). However, the impact of aICH on the functional outcome remains widely unclear. In this study, we aimed at identifying predictors for aICH and analyzing its impact on functional outcome. Patients with AIS due to large artery occlusion in the anterior circulation treated with successful ET were enrolled in a tertiary stroke center. Patients with aICH or without intracerebral hemorrhage were included according to post-treatment CT performed within 72 h; 100 consecutive patients fulfilled the inclusion criteria and 30% classified with aICH. In logistic regression analysis, lower collateral score (OR 0.24; 95% CI 0.12–0.46, p < 0.0001) was significantly associated with aICH. Less patients with aICH achieved an independent outcome (mRS 0–2, 16.7% vs. 44.3%, p = 0.007). Poor outcome (mRS 4–6) was significantly higher in patients with aICH (41.4% vs. 70%, p = 0.021). Patients with aICH had a lower ratio of independent outcome (OR 0.23, 95% CI 0.05–0.1.05, p = 0.041) than without ICH. There were no differences concerning poor outcome (p = 0.5). Lower collateral status was a strong independent predictor for aICH. aICH after successful ET may decrease the likelihood of an independent functional outcome without influencing poor outcome.
无症状脑出血(aICH)是急性缺血性卒中(AIS)行血管内取栓术(ET)的常见现象。然而，aICH对功能结果的影响仍不清楚。在这项研究中，我们旨在确定aICH的预测因素并分析其对功能结局的影响。经ET治疗成功的前循环大动脉闭塞导致AIS的患者被纳入三级卒中中心。根据治疗后72h内CT检查纳入有aICH或无脑出血的患者;连续100例患者符合纳入标准，其中30%为aICH。logistic回归分析中，侧支评分较低(OR 0.24;95% CI 0.12-0.46, p < 0.0001)与aICH显著相关。获得独立结局的aICH患者较少(mRS 0-2, 16.7%比44.3%，p = 0.007)。不良预后(mRS 4-6)在aICH患者中明显较高(41.4%比70%，p = 0.021)。缺血性脑出血患者的独立结局比(OR 0.23, 95% CI 0.05-0.1.05, p = 0.041)低于非缺血性脑出血患者。在不良预后方面没有差异(p = 0.5)。较低的侧支状态是aICH强有力的独立预测因子。ET成功后的急性脑出血可能会降低独立功能预后的可能性，但不会影响不良预后。
{"title":"Clinical relevance of asymptomatic intracerebral hemorrhage post thrombectomy depends on angiographic collateral score","authors":"J. Nawabi, H. Kniep, G. Broocks, T. Faizy, G. Schön, G. Thomalla, J. Fiehler, U. Hanning","doi":"10.1177/0271678X19871253","DOIUrl":"https://doi.org/10.1177/0271678X19871253","url":null,"abstract":"Asymptomatic intracerebral hemorrhage (aICH) is a common phenomenon in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (ET). However, the impact of aICH on the functional outcome remains widely unclear. In this study, we aimed at identifying predictors for aICH and analyzing its impact on functional outcome. Patients with AIS due to large artery occlusion in the anterior circulation treated with successful ET were enrolled in a tertiary stroke center. Patients with aICH or without intracerebral hemorrhage were included according to post-treatment CT performed within 72 h; 100 consecutive patients fulfilled the inclusion criteria and 30% classified with aICH. In logistic regression analysis, lower collateral score (OR 0.24; 95% CI 0.12–0.46, p < 0.0001) was significantly associated with aICH. Less patients with aICH achieved an independent outcome (mRS 0–2, 16.7% vs. 44.3%, p = 0.007). Poor outcome (mRS 4–6) was significantly higher in patients with aICH (41.4% vs. 70%, p = 0.021). Patients with aICH had a lower ratio of independent outcome (OR 0.23, 95% CI 0.05–0.1.05, p = 0.041) than without ICH. There were no differences concerning poor outcome (p = 0.5). Lower collateral status was a strong independent predictor for aICH. aICH after successful ET may decrease the likelihood of an independent functional outcome without influencing poor outcome.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"36 1","pages":"1599 - 1607"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84777037","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 : 2020-08-01DOI: 10.1177/0271678X19874134
James R Goodman, Jeffrey J. Iliff
Despite the recent description of meningeal lymphatic vessels draining solutes from the brain interstitium and cerebrospinal fluid (CSF), the physiological factors governing cranial lymphatic efflux remain largely unexplored. In agreement with recent findings, cervical lymphatic drainage of 70 kD and 2000 kD fluorescent tracers injected into the adult mouse cortex was significantly impaired in the anesthetized compared to waking animals (tracer distribution across 2.1 ± 4.5% and 23.7 ± 15.8% of deep cervical lymph nodes, respectively); however, free-breathing anesthetized mice were markedly hypercapnic and acidemic (paCO2 = 64 ± 8 mmHg; pH = 7.22 ± 0.05). Mechanical ventilation normalized arterial blood gases in anesthetized animals, and rescued lymphatic efflux of interstitial solutes in anesthetized mice. Experimental hypercapnia blocked cervical lymphatic efflux of intraparenchymal tracers. When tracers were injected into the subarachnoid CSF compartment, glymphatic influx into brain tissue was virtually abolished by hypercapnia, while lymphatic drainage was not appreciably altered. These findings demonstrate that cervical lymphatic drainage of interstitial solutes is, in part, regulated by upstream changes in glymphatic CSF-interstitial fluid exchange. Further, they suggest that maintaining physiological blood gas values in studies of glymphatic exchange and meningeal lymphatic drainage may be critical to defining the physiological regulation of these processes.
{"title":"Vasomotor influences on glymphatic-lymphatic coupling and solute trafficking in the central nervous system","authors":"James R Goodman, Jeffrey J. Iliff","doi":"10.1177/0271678X19874134","DOIUrl":"https://doi.org/10.1177/0271678X19874134","url":null,"abstract":"Despite the recent description of meningeal lymphatic vessels draining solutes from the brain interstitium and cerebrospinal fluid (CSF), the physiological factors governing cranial lymphatic efflux remain largely unexplored. In agreement with recent findings, cervical lymphatic drainage of 70 kD and 2000 kD fluorescent tracers injected into the adult mouse cortex was significantly impaired in the anesthetized compared to waking animals (tracer distribution across 2.1 ± 4.5% and 23.7 ± 15.8% of deep cervical lymph nodes, respectively); however, free-breathing anesthetized mice were markedly hypercapnic and acidemic (paCO2 = 64 ± 8 mmHg; pH = 7.22 ± 0.05). Mechanical ventilation normalized arterial blood gases in anesthetized animals, and rescued lymphatic efflux of interstitial solutes in anesthetized mice. Experimental hypercapnia blocked cervical lymphatic efflux of intraparenchymal tracers. When tracers were injected into the subarachnoid CSF compartment, glymphatic influx into brain tissue was virtually abolished by hypercapnia, while lymphatic drainage was not appreciably altered. These findings demonstrate that cervical lymphatic drainage of interstitial solutes is, in part, regulated by upstream changes in glymphatic CSF-interstitial fluid exchange. Further, they suggest that maintaining physiological blood gas values in studies of glymphatic exchange and meningeal lymphatic drainage may be critical to defining the physiological regulation of these processes.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"16 1","pages":"1724 - 1734"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86399396","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 : 2020-08-01DOI: 10.1177/0271678X19874295
A. Hougaard, Samaira Younis, Afrim Iljazi, K. Haanes, U. Lindberg, Mark B. Vestergaard, F. Amin, K. Sugimoto, L. Kruse, C. Ayata, M. Ashina
Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide released from vascular endothelium. ET-1 plays a major role in cerebrovascular disorders and likely worsens the outcome of acute ischaemic stroke and aneurismal subarachnoid haemorrhage through vasoconstriction and cerebral blood flow (CBF) reduction. Disorders that increase the risk of stroke, including hypertension, diabetes mellitus, and acute myocardial infarction, are associated with increased plasma levels of ET-1. The in vivo human cerebrovascular effects of systemic ET-1 infusion have not previously been investigated. In a two-way crossover, randomized, double-blind design, we used advanced 3 tesla MRI methods to investigate the effects of high-dose intravenous ET-1 on intra- and extracranial artery circumferences, global and regional CBF, and cerebral metabolic rate of oxygen (CMRO2) in 14 healthy volunteers. Following ET-1 infusion, we observed a 14% increase of mean arterial blood pressure, a 5% decrease of middle cerebral artery (MCA) circumference, but no effects on extracerebral arteries and no effects on CBF or CMRO2. Collectively, the findings indicate MCA constriction secondarily to blood pressure increase and not due to a direct vasoconstrictor effect of ET-1. We suggest that, as opposed to ET-1 in the subarachnoid space, intravascular ET-1 does not exert direct cerebrovascular effects in humans.
{"title":"Cerebrovascular effects of endothelin-1 investigated using high-resolution magnetic resonance imaging in healthy volunteers","authors":"A. Hougaard, Samaira Younis, Afrim Iljazi, K. Haanes, U. Lindberg, Mark B. Vestergaard, F. Amin, K. Sugimoto, L. Kruse, C. Ayata, M. Ashina","doi":"10.1177/0271678X19874295","DOIUrl":"https://doi.org/10.1177/0271678X19874295","url":null,"abstract":"Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide released from vascular endothelium. ET-1 plays a major role in cerebrovascular disorders and likely worsens the outcome of acute ischaemic stroke and aneurismal subarachnoid haemorrhage through vasoconstriction and cerebral blood flow (CBF) reduction. Disorders that increase the risk of stroke, including hypertension, diabetes mellitus, and acute myocardial infarction, are associated with increased plasma levels of ET-1. The in vivo human cerebrovascular effects of systemic ET-1 infusion have not previously been investigated. In a two-way crossover, randomized, double-blind design, we used advanced 3 tesla MRI methods to investigate the effects of high-dose intravenous ET-1 on intra- and extracranial artery circumferences, global and regional CBF, and cerebral metabolic rate of oxygen (CMRO2) in 14 healthy volunteers. Following ET-1 infusion, we observed a 14% increase of mean arterial blood pressure, a 5% decrease of middle cerebral artery (MCA) circumference, but no effects on extracerebral arteries and no effects on CBF or CMRO2. Collectively, the findings indicate MCA constriction secondarily to blood pressure increase and not due to a direct vasoconstrictor effect of ET-1. We suggest that, as opposed to ET-1 in the subarachnoid space, intravascular ET-1 does not exert direct cerebrovascular effects in humans.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"17 1","pages":"1685 - 1694"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87155392","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 : 2020-07-01DOI: 10.1177/0271678X19868880
Yutaro Hoshi, Yasuo Uchida, T. Kuroda, M. Tachikawa, P. Couraud, Takashi Suzuki, T. Terasaki
The purpose of this study was to clarify the roles of ERM proteins (ezrin/radixin/moesin) in the regulation of membrane localization and transport activity of transporters at the human blood–brain barrier (BBB). Ezrin or moesin knockdown in a human in vitro BBB model cell line (hCMEC/D3) reduced both BCRP and GLUT1 protein expression levels on the plasma membrane. Radixin knockdown reduced not only BCRP and GLUT1, but also P-gp membrane expression. These results indicate that P-gp, BCRP and GLUT1 proteins are maintained on the plasma membrane via different ERM proteins. Furthermore, moesin knockdown caused the largest decrease of P-gp and BCRP efflux activity among the ERM proteins, whereas GLUT1 influx activity was similarly reduced by knockdown of each ERM protein. To investigate how moesin knockdown reduced P-gp efflux activity without loss of P-gp from the plasma membrane, we examined the role of PKCβI. PKCβI increased P-gp phosphorylation and reduced P-gp efflux activity. Radixin and moesin proteins were detected in isolated human brain capillaries, and their protein abundances were within a 3-fold range, compared with those in hCMEC/D3 cell line. These findings may mean that ezrin, radixin and moesin maintain the functions of different transporters in different ways at the human BBB.
{"title":"Distinct roles of ezrin, radixin and moesin in maintaining the plasma membrane localizations and functions of human blood–brain barrier transporters","authors":"Yutaro Hoshi, Yasuo Uchida, T. Kuroda, M. Tachikawa, P. Couraud, Takashi Suzuki, T. Terasaki","doi":"10.1177/0271678X19868880","DOIUrl":"https://doi.org/10.1177/0271678X19868880","url":null,"abstract":"The purpose of this study was to clarify the roles of ERM proteins (ezrin/radixin/moesin) in the regulation of membrane localization and transport activity of transporters at the human blood–brain barrier (BBB). Ezrin or moesin knockdown in a human in vitro BBB model cell line (hCMEC/D3) reduced both BCRP and GLUT1 protein expression levels on the plasma membrane. Radixin knockdown reduced not only BCRP and GLUT1, but also P-gp membrane expression. These results indicate that P-gp, BCRP and GLUT1 proteins are maintained on the plasma membrane via different ERM proteins. Furthermore, moesin knockdown caused the largest decrease of P-gp and BCRP efflux activity among the ERM proteins, whereas GLUT1 influx activity was similarly reduced by knockdown of each ERM protein. To investigate how moesin knockdown reduced P-gp efflux activity without loss of P-gp from the plasma membrane, we examined the role of PKCβI. PKCβI increased P-gp phosphorylation and reduced P-gp efflux activity. Radixin and moesin proteins were detected in isolated human brain capillaries, and their protein abundances were within a 3-fold range, compared with those in hCMEC/D3 cell line. These findings may mean that ezrin, radixin and moesin maintain the functions of different transporters in different ways at the human BBB.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"40 1","pages":"1533 - 1545"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83260239","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 : 2020-07-01DOI: 10.1177/0271678X19867276
Erin K. Englund, M. Fernández-Seara, Ana E. Rodriguez-Soto, Hyunyeol Lee, Zachary B. Rodgers, M. Vidorreta, J. Detre, F. Wehrli
Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation (Y v ) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Y v -based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Y v via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Y v -based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between (p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.
{"title":"Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation","authors":"Erin K. Englund, M. Fernández-Seara, Ana E. Rodriguez-Soto, Hyunyeol Lee, Zachary B. Rodgers, M. Vidorreta, J. Detre, F. Wehrli","doi":"10.1177/0271678X19867276","DOIUrl":"https://doi.org/10.1177/0271678X19867276","url":null,"abstract":"Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation (Y v ) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Y v -based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Y v via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Y v -based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between (p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"55 1","pages":"1501 - 1516"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77074682","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 : 2020-07-01Epub Date: 2019-07-25DOI: 10.1177/0271678X19865916
Marco Duering, Ruth Adam, Frank A Wollenweber, Anna Bayer-Karpinska, Ebru Baykara, Leidy Y Cubillos-Pinilla, Benno Gesierich, Miguel Á Araque Caballero, Sophia Stoecklein, Michael Ewers, Ofer Pasternak, Martin Dichgans
The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline (n = 45), six months (n = 45), and three years (n = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, p = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.
{"title":"Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis.","authors":"Marco Duering, Ruth Adam, Frank A Wollenweber, Anna Bayer-Karpinska, Ebru Baykara, Leidy Y Cubillos-Pinilla, Benno Gesierich, Miguel Á Araque Caballero, Sophia Stoecklein, Michael Ewers, Ofer Pasternak, Martin Dichgans","doi":"10.1177/0271678X19865916","DOIUrl":"10.1177/0271678X19865916","url":null,"abstract":"<p><p>The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline (<i>n</i> = 45), six months (<i>n</i> = 45), and three years (<i>n</i> = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, <i>p</i> = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.</p>","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"8 1","pages":"1482-1491"},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79221490","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}
Pub Date : 2020-06-01DOI: 10.1177/0271678X19865219
R. Raychev, D. Liebeskind, A. Yoo, M. Rasmussen, D. Arnaudov, Scott C. Brown, J. Saver, C. Simonsen
Collateral circulation plays a pivotal role in acute ischemic stroke due to large vessel occlusion (LVO) and may be affected by multiple variables during sedation for endovascular therapy (EVT). We conducted detailed analyses of the GOLIATH trial to identify predictors of collateral circulation grade and infarct growth. We also modified the ASITN collateral grading scale and sought to determine its impact on clinical outcome and infarct growth. Multivariable analysis was used to identify predictors of collaterals and infarct growth. Ordinal analysis demonstrated nominal, but non-significant association between modified ASITN scale and infarct growth. Among all analyzed baseline clinical and procedural variables, the most significant predictors of infarct growth at 24 h were phenylephrine dose (estimate 6.78; p = 0.014) and baseline infarct volume (estimate 0.93; p = 0.03). The most significant predictors of worse collateral grade were mean arterial pressure (MAP) <70 mmHg (OR 0.35; p = 0.048) and baseline infarct volume (OR 0.96; p = 0.003). Hypotension during sedation for EVT for LVO negatively impacts collateral circulation, while higher pressor dose is a strong predictor of infarct growth. Avoidance of anesthesia-induced hypotension and consequent need for pressor therapy may prevent collateral failure and minimize infarct growth.
{"title":"Physiologic predictors of collateral circulation and infarct growth during anesthesia – Detailed analyses of the GOLIATH trial","authors":"R. Raychev, D. Liebeskind, A. Yoo, M. Rasmussen, D. Arnaudov, Scott C. Brown, J. Saver, C. Simonsen","doi":"10.1177/0271678X19865219","DOIUrl":"https://doi.org/10.1177/0271678X19865219","url":null,"abstract":"Collateral circulation plays a pivotal role in acute ischemic stroke due to large vessel occlusion (LVO) and may be affected by multiple variables during sedation for endovascular therapy (EVT). We conducted detailed analyses of the GOLIATH trial to identify predictors of collateral circulation grade and infarct growth. We also modified the ASITN collateral grading scale and sought to determine its impact on clinical outcome and infarct growth. Multivariable analysis was used to identify predictors of collaterals and infarct growth. Ordinal analysis demonstrated nominal, but non-significant association between modified ASITN scale and infarct growth. Among all analyzed baseline clinical and procedural variables, the most significant predictors of infarct growth at 24 h were phenylephrine dose (estimate 6.78; p = 0.014) and baseline infarct volume (estimate 0.93; p = 0.03). The most significant predictors of worse collateral grade were mean arterial pressure (MAP) <70 mmHg (OR 0.35; p = 0.048) and baseline infarct volume (OR 0.96; p = 0.003). Hypotension during sedation for EVT for LVO negatively impacts collateral circulation, while higher pressor dose is a strong predictor of infarct growth. Avoidance of anesthesia-induced hypotension and consequent need for pressor therapy may prevent collateral failure and minimize infarct growth.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"39 1","pages":"1203 - 1212"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81090016","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 : 2020-06-01DOI: 10.1177/0271678X19865917
Godwin K. Dogbevia, H. Grasshoff, A. Othman, Anke Penno, M. Schwaninger
In Tay-Sachs and Sandhoff disease, a deficiency of the lysosomal enzyme β-hexosaminidase causes GM2 and other gangliosides to accumulate in neurons and triggers neurodegeneration. Although the pathology centers on neurons, β-hexosaminidase is mainly expressed outside of neurons, suggesting that gene therapy of these diseases should target non-neuronal cells to reconstitute physiological conditions. Here, we tested in Hexb−/− mice, a model of Sandhoff disease, to determine whether endothelial expression of the genes for human β-hexosaminidase subunit A and B (HEXA, HEXB) is able to reduce disease symptoms and prolong survival of the affected mice. The brain endothelial selective vectors AAV-BR1-CAG-HEXA and AAV-BR1-CAG-HEXB transduced brain endothelial cells, which subsequently released β-hexosaminidase enzyme. In vivo intravenous administration of the gene vectors to adult and neonatal mice prolonged survival. They improved neurological function and reduced accumulation of the ganglioside GM2 and the glycolipid GA2 as well as astrocytic activation. Overall, the data demonstrate that endothelial cells are a suitable target for intravenous gene therapy of GM2 gangliosidoses and possibly other lysosomal storage disorders.
{"title":"Brain endothelial specific gene therapy improves experimental Sandhoff disease","authors":"Godwin K. Dogbevia, H. Grasshoff, A. Othman, Anke Penno, M. Schwaninger","doi":"10.1177/0271678X19865917","DOIUrl":"https://doi.org/10.1177/0271678X19865917","url":null,"abstract":"In Tay-Sachs and Sandhoff disease, a deficiency of the lysosomal enzyme β-hexosaminidase causes GM2 and other gangliosides to accumulate in neurons and triggers neurodegeneration. Although the pathology centers on neurons, β-hexosaminidase is mainly expressed outside of neurons, suggesting that gene therapy of these diseases should target non-neuronal cells to reconstitute physiological conditions. Here, we tested in Hexb−/− mice, a model of Sandhoff disease, to determine whether endothelial expression of the genes for human β-hexosaminidase subunit A and B (HEXA, HEXB) is able to reduce disease symptoms and prolong survival of the affected mice. The brain endothelial selective vectors AAV-BR1-CAG-HEXA and AAV-BR1-CAG-HEXB transduced brain endothelial cells, which subsequently released β-hexosaminidase enzyme. In vivo intravenous administration of the gene vectors to adult and neonatal mice prolonged survival. They improved neurological function and reduced accumulation of the ganglioside GM2 and the glycolipid GA2 as well as astrocytic activation. Overall, the data demonstrate that endothelial cells are a suitable target for intravenous gene therapy of GM2 gangliosidoses and possibly other lysosomal storage disorders.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"44 1","pages":"1338 - 1350"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73790593","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 : 2020-06-01DOI: 10.1177/0271678X19867908
K. Shinozuka, N. Tajiri, H. Ishikawa, Julian P. Tuazon, Jea-Young Lee, P. Sanberg, Sydney Zarriello, Sydney Corey, Y. Kaneko, C. Borlongan
Rodents display “empathy” defined as perceived physical pain or psychological stress by cagemates when co-experiencing socially distinct traumatic events. The present study tested the hypothesis that empathy occurs in adult rats subjected to an experimental neurological disorder, by allowing co-experience of stroke with cagemates. Psychological stress was measured by general locomotor activity, Rat Grimace Scale (RGS), and plasma corticosterone. Physiological correlates were measured by Western blot analysis of advanced glycation endproducts (AGE)-related proteins in the thymus. General locomotor activity was impaired in stroke animals and in non-stroke rats housed with stroke rats suggesting transfer of behavioral manifestation of psychological stress from an injured animal to a non-injured animal leading to social inhibition. RGS was higher in stroke rats regardless of social settings. Plasma corticosterone levels at day 3 after stroke were significantly higher in stroke animals housed with stroke rats, but not with non-stroke rats, indicating that empathy upregulated physiological stress level. The expression of five proteins related to AGE in the thymus reflected the observed pattern of general locomotor activity, RGS, and plasma corticosterone levels. These results indicate that stroke-induced psychological stress manifested on both the behavioral and physiological levels and appeared to be affected by empathy-associated social settings.
{"title":"Empathy in stroke rats is modulated by social settings","authors":"K. Shinozuka, N. Tajiri, H. Ishikawa, Julian P. Tuazon, Jea-Young Lee, P. Sanberg, Sydney Zarriello, Sydney Corey, Y. Kaneko, C. Borlongan","doi":"10.1177/0271678X19867908","DOIUrl":"https://doi.org/10.1177/0271678X19867908","url":null,"abstract":"Rodents display “empathy” defined as perceived physical pain or psychological stress by cagemates when co-experiencing socially distinct traumatic events. The present study tested the hypothesis that empathy occurs in adult rats subjected to an experimental neurological disorder, by allowing co-experience of stroke with cagemates. Psychological stress was measured by general locomotor activity, Rat Grimace Scale (RGS), and plasma corticosterone. Physiological correlates were measured by Western blot analysis of advanced glycation endproducts (AGE)-related proteins in the thymus. General locomotor activity was impaired in stroke animals and in non-stroke rats housed with stroke rats suggesting transfer of behavioral manifestation of psychological stress from an injured animal to a non-injured animal leading to social inhibition. RGS was higher in stroke rats regardless of social settings. Plasma corticosterone levels at day 3 after stroke were significantly higher in stroke animals housed with stroke rats, but not with non-stroke rats, indicating that empathy upregulated physiological stress level. The expression of five proteins related to AGE in the thymus reflected the observed pattern of general locomotor activity, RGS, and plasma corticosterone levels. These results indicate that stroke-induced psychological stress manifested on both the behavioral and physiological levels and appeared to be affected by empathy-associated social settings.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"39 1","pages":"1182 - 1192"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91194626","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 : 2020-06-01DOI: 10.1177/0271678X19862182
Pei-Hsin Wu, Ana E. Rodriguez-Soto, Zachary B. Rodgers, Erin K. Englund, A. Wiemken, M. Langham, J. Detre, R. Schwab, Wensheng Guo, F. Wehrli
Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO2. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min2/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s2, P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.
阻塞性睡眠呼吸暂停(OSA)的特点是睡眠时气道间歇性阻塞。脑血管反应性(CVR)是脑血管对血管活性刺激(如二氧化碳增加)作出反应能力的指标。我们假设OSA改变CVR，以屏气指数(BHI)表示，BHI定义为在控制屏气刺激期间CBF或BOLD信号的变化率，通过高碳酸血症和低氧模拟自发呼吸暂停。在37名OSA和23名匹配的非睡眠呼吸暂停(NSA)受试者中，我们在连续5次24秒的BH刺激之前、期间和之间获得了高时间分辨率的CBF和BOLD MRI数据，每次平均产生一个BHI值。由于全脑CBF(78.6±29.6 vs. 60.0±20.0 mL/min / 2/100 g, P = 0.010)和上矢状窦血流速度(0.48±0.18 vs. 0.36±0.10 cm/s2, P = 0.014)， OSA患者的BHI高于NSA患者。同样，OSA中基于bold的BHI在全脑(0.19±0.08比0.15±0.03%/s, P = 0.009)、灰质(0.22±0.09比0.17±0.03%/s, P = 0.011)和白质(0.14±0.06比0.10±0.02%/s, P = 0.010)中更高。更大的CVR目前尚不清楚，但可能代表大脑在间歇性呼吸暂停期间维持氧气供应的代偿机制。
{"title":"MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea","authors":"Pei-Hsin Wu, Ana E. Rodriguez-Soto, Zachary B. Rodgers, Erin K. Englund, A. Wiemken, M. Langham, J. Detre, R. Schwab, Wensheng Guo, F. Wehrli","doi":"10.1177/0271678X19862182","DOIUrl":"https://doi.org/10.1177/0271678X19862182","url":null,"abstract":"Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO2. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min2/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s2, P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"14 1","pages":"1328 - 1337"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87298396","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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