Pub Date : 2022-04-11DOI: 10.1177/0271678X221093579
C. Mayer, Felix L. Nägele, M. Petersen, B. Frey, U. Hanning, O. Pasternak, E. Petersen, C. Gerloff, G. Thomalla, B. Cheng
In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.
{"title":"Free-water diffusion MRI detects structural alterations surrounding white matter hyperintensities in the early stage of cerebral small vessel disease","authors":"C. Mayer, Felix L. Nägele, M. Petersen, B. Frey, U. Hanning, O. Pasternak, E. Petersen, C. Gerloff, G. Thomalla, B. Cheng","doi":"10.1177/0271678X221093579","DOIUrl":"https://doi.org/10.1177/0271678X221093579","url":null,"abstract":"In cerebral small vessel disease (CSVD), both white matter hyperintensities (WMH) of presumed vascular origin and the normal-appearing white matter (NAWM) contain microstructural brain alterations on diffusion-weighted MRI (DWI). Contamination of DWI-derived metrics by extracellular free-water can be corrected with free-water (FW) imaging. We investigated the alterations in FW and FW-corrected fractional anisotropy (FA-t) in WMH and surrounding tissue and their association with cerebrovascular risk factors. We analysed 1,000 MRI datasets from the Hamburg City Health Study. DWI was used to generate FW and FA-t maps. WMH masks were segmented on FLAIR and T1-weighted MRI and dilated repeatedly to create 8 NAWM masks representing increasing distance from WMH. Linear models were applied to compare FW and FA-t across WMH and NAWM masks and in association with cerebrovascular risk. Median age was 64 ± 14 years. FW and FA-t were altered 8 mm and 12 mm beyond WMH, respectively. Smoking was significantly associated with FW in NAWM (p = 0.008) and FA-t in WMH (p = 0.008) and in NAWM (p = 0.003) while diabetes and hypertension were not. Further research is necessary to examine whether FW and FA-t alterations in NAWM are predictors for developing WMH.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"61 1","pages":"1707 - 1718"},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73681865","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 : 2022-03-29DOI: 10.1177/0271678X221090747
P. Eide, A. Pripp, Benedikte Berge, H. Hrubos-Strøm, G. Ringstad, L. Valnes
Chronic sleep disturbance is a risk factor for dementia disease, possibly due to impaired sleep-dependent clearance of toxic metabolic by-products. We compared enrichment of a cerebrospinal fluid (CSF) tracer within brain of patients reporting good or poor sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Tracer enrichment in a selection of brain regions was assessed using multiphase magnetic resonance imaging up to 48 hours after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml) serving as tracer. Tracer enrichment differed between patients with good (PSQI ≤5) and poor (PSQI >5) sleep quality in a cohort of non-dementia individuals (n = 44; age 42.3 ± 14.5 years), and in patients with the dementia subtype idiopathic normal pressure hydrocephalus (n = 24; age 71.0 ± 4.9 years). Sleep impairment was associated with increased CSF tracer enrichment in several brain regions. Cortical brain volume as well as entorhinal cortex thickness was reduced in the oldest cohort and was correlated with the severity of sleep disturbance and the degree of cortical tracer enrichment. We suggest chronic sleep disturbance is accompanied by altered glymphatic function along enlarged perivascular spaces.
{"title":"Altered glymphatic enhancement of cerebrospinal fluid tracer in individuals with chronic poor sleep quality","authors":"P. Eide, A. Pripp, Benedikte Berge, H. Hrubos-Strøm, G. Ringstad, L. Valnes","doi":"10.1177/0271678X221090747","DOIUrl":"https://doi.org/10.1177/0271678X221090747","url":null,"abstract":"Chronic sleep disturbance is a risk factor for dementia disease, possibly due to impaired sleep-dependent clearance of toxic metabolic by-products. We compared enrichment of a cerebrospinal fluid (CSF) tracer within brain of patients reporting good or poor sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Tracer enrichment in a selection of brain regions was assessed using multiphase magnetic resonance imaging up to 48 hours after intrathecal administration of the contrast agent gadobutrol (0.5 ml of 1 mmol/ml) serving as tracer. Tracer enrichment differed between patients with good (PSQI ≤5) and poor (PSQI >5) sleep quality in a cohort of non-dementia individuals (n = 44; age 42.3 ± 14.5 years), and in patients with the dementia subtype idiopathic normal pressure hydrocephalus (n = 24; age 71.0 ± 4.9 years). Sleep impairment was associated with increased CSF tracer enrichment in several brain regions. Cortical brain volume as well as entorhinal cortex thickness was reduced in the oldest cohort and was correlated with the severity of sleep disturbance and the degree of cortical tracer enrichment. We suggest chronic sleep disturbance is accompanied by altered glymphatic function along enlarged perivascular spaces.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"7 1","pages":"1676 - 1692"},"PeriodicalIF":0.0,"publicationDate":"2022-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79080437","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 : 2022-03-15DOI: 10.1177/0271678X211065204
Sam C Barnes, R. Panerai, L. Beishon, M. Hanby, T. Robinson, V. Haunton
Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients. 55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (EtCO2; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO2 and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation. Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.
帕金森病(PD)是一种常见的神经退行性疾病，但对该患者群体的脑血流动力学知之甚少。先前评估动态大脑自动调节(dCA)、神经血管耦合(NVC)和血管运动反应(VMR)的研究得出了相互矛盾的结果。通过使用多变量模型，我们旨在确定PD患者的脑血流量(CBF)调节是否受损。健康对照(HC) 55例，PD患者49例。PD受试者在一段时间停止服用抗帕金森药物后进行了第二次记录。连续双侧经颅多普勒测量大脑中动脉，每搏平均动脉血压(MAP;Finapres)，心率(HR;潮末CO2 (EtCO2;摄摄)。5分钟基线期后，进行被动运动模式，包括60秒的肘关节屈曲。多元模型量化了MAP、ETCO2和神经刺激对脑血流速度(CBFV)变化的贡献。量化dCA、VMR和NVC以评估CBF调节的完整性。神经刺激是主要的输入。PD组dCA、NVC、VMR均较HC组受损(p < 0.01, p = 0.04, p < 0.01)。我们的数据表明PD可能与CBF调节下降有关。这需要使用不同的神经刺激进一步评估。
{"title":"Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis","authors":"Sam C Barnes, R. Panerai, L. Beishon, M. Hanby, T. Robinson, V. Haunton","doi":"10.1177/0271678X211065204","DOIUrl":"https://doi.org/10.1177/0271678X211065204","url":null,"abstract":"Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients. 55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (EtCO2; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO2 and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation. Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"98 1","pages":"1547 - 1558"},"PeriodicalIF":0.0,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90528214","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 : 2022-03-03DOI: 10.1177/0271678X221080324
M. Briquet, A. Rocher, Maxime Alessandri, Nadia Rosenberg, Haíssa de Castro Abrantes, Joel Wellbourne-Wood, Céline Schmuziger, V. Ginet, J. Puyal, E. Pralong, R. Daniel, S. Offermanns, J. Chatton
Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca2+ spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy.
{"title":"Activation of lactate receptor HCAR1 down-modulates neuronal activity in rodent and human brain tissue","authors":"M. Briquet, A. Rocher, Maxime Alessandri, Nadia Rosenberg, Haíssa de Castro Abrantes, Joel Wellbourne-Wood, Céline Schmuziger, V. Ginet, J. Puyal, E. Pralong, R. Daniel, S. Offermanns, J. Chatton","doi":"10.1177/0271678X221080324","DOIUrl":"https://doi.org/10.1177/0271678X221080324","url":null,"abstract":"Lactate can be used by neurons as an energy substrate to support their activity. Evidence suggests that lactate also acts on a metabotropic receptor called HCAR1, first described in the adipose tissue. Whether HCAR1 also modulates neuronal circuits remains unclear. In this study, using qRT-PCR, we show that HCAR1 is present in the human brain of epileptic patients who underwent resective surgery. In brain slices from these patients, pharmacological HCAR1 activation using a non-metabolized agonist decreased the frequency of both spontaneous neuronal Ca2+ spiking and excitatory post-synaptic currents (sEPSCs). In mouse brains, we found HCAR1 expression in different regions using a fluorescent reporter mouse line and in situ hybridization. In the dentate gyrus, HCAR1 is mainly present in mossy cells, key players in the hippocampal excitatory circuitry and known to be involved in temporal lobe epilepsy. By using whole-cell patch clamp recordings in mouse and rat slices, we found that HCAR1 activation causes a decrease in excitability, sEPSCs, and miniature EPSCs frequency of granule cells, the main output of mossy cells. Overall, we propose that lactate can be considered a neuromodulator decreasing synaptic activity in human and rodent brains, which makes HCAR1 an attractive target for the treatment of epilepsy.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"57 1","pages":"1650 - 1665"},"PeriodicalIF":0.0,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80225715","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 : 2020-10-01DOI: 10.1177/0271678X19883599
Antoine Anfray, Antoine Drieu, Vincent Hingot, Y. Hommet, Mervé Yetim, M. Rubio, T. Deffieux, M. Tanter, C. Orset, D. Vivien
The increase of cerebral blood flow evoked by neuronal activity is essential to ensure enough energy supply to the brain. In the neurovascular unit, endothelial cells are ideally placed to regulate key neurovascular functions of the brain. Nevertheless, some outstanding questions remain about their exact role neurovascular coupling (NVC). Here, we postulated that the tissue-type plasminogen activator (tPA) present in the circulation might contribute to NVC by a mechanism dependent of its interaction with endothelial N-Methyl-D-Aspartate Receptor (NMDAR). To address this question, we used pharmacological and genetic approaches to interfere with vascular tPA-dependent NMDAR signaling, combined with laser speckle flowmetry, intravital microscopy and ultrafast functional ultrasound in vivo imaging. We found that the tPA present in the blood circulation is capable of potentiating the cerebral blood flow increase induced by the activation of the mouse somatosensorial cortex, and that this effect is mediated by a tPA-dependent activation of NMDAR expressed at the luminal part of endothelial cells of arteries. Although blood molecules, such as acetylcholine, bradykinin or ATP are known to regulate vascular tone and induce vessel dilation, our present data provide the first evidence that circulating tPA is capable of influencing neurovascular coupling (NVC).
神经元活动引起的脑血流量增加是保证大脑足够能量供应的必要条件。在神经血管单元中，内皮细胞被理想地放置来调节大脑的关键神经血管功能。然而，神经血管耦合(NVC)的确切作用仍存在一些悬而未决的问题。在这里，我们假设循环中存在的组织型纤溶酶原激活剂(tPA)可能通过其与内皮n -甲基- d -天冬氨酸受体(NMDAR)相互作用的机制促进NVC。为了解决这个问题，我们使用药理学和遗传学方法来干扰血管tpa依赖的NMDAR信号，并结合激光散斑血流法、活体显微镜和超快速功能超声体内成像。我们发现，血液循环中存在的tPA能够增强由小鼠体感觉皮层激活引起的脑血流量增加，并且这种作用是由tPA依赖性激活的NMDAR介导的，NMDAR表达于动脉内皮细胞的管腔部分。虽然已知血液分子，如乙酰胆碱、缓激肽或ATP可以调节血管张力并诱导血管扩张，但我们目前的数据首次提供了循环tPA能够影响神经血管偶联(NVC)的证据。
{"title":"Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors","authors":"Antoine Anfray, Antoine Drieu, Vincent Hingot, Y. Hommet, Mervé Yetim, M. Rubio, T. Deffieux, M. Tanter, C. Orset, D. Vivien","doi":"10.1177/0271678X19883599","DOIUrl":"https://doi.org/10.1177/0271678X19883599","url":null,"abstract":"The increase of cerebral blood flow evoked by neuronal activity is essential to ensure enough energy supply to the brain. In the neurovascular unit, endothelial cells are ideally placed to regulate key neurovascular functions of the brain. Nevertheless, some outstanding questions remain about their exact role neurovascular coupling (NVC). Here, we postulated that the tissue-type plasminogen activator (tPA) present in the circulation might contribute to NVC by a mechanism dependent of its interaction with endothelial N-Methyl-D-Aspartate Receptor (NMDAR). To address this question, we used pharmacological and genetic approaches to interfere with vascular tPA-dependent NMDAR signaling, combined with laser speckle flowmetry, intravital microscopy and ultrafast functional ultrasound in vivo imaging. We found that the tPA present in the blood circulation is capable of potentiating the cerebral blood flow increase induced by the activation of the mouse somatosensorial cortex, and that this effect is mediated by a tPA-dependent activation of NMDAR expressed at the luminal part of endothelial cells of arteries. Although blood molecules, such as acetylcholine, bradykinin or ATP are known to regulate vascular tone and induce vessel dilation, our present data provide the first evidence that circulating tPA is capable of influencing neurovascular coupling (NVC).","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"23 1","pages":"2038 - 2054"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74466610","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 : 2020-10-01DOI: 10.1177/0271678X19882264
David L Bernstein, Viviana Zuluaga-Ramirez, Sachin Gajghate, N. Reichenbach, B. Polyak, Y. Persidsky, Slava Rom
Most neurological diseases, including stroke, lead to some degree of blood–brain barrier (BBB) dysfunction. A significant portion of BBB injury is caused by inflammation, due to pro-inflammatory factors produced in the brain, and by leukocyte engagement of the brain endothelium. Recently, microRNAs (miRNAs) have appeared as major regulators of inflammation-induced changes to gene expression in the microvascular endothelial cells (BMVEC) that comprise the BBB. However, miRNAs’ role during cerebral ischemia/reperfusion is still underexplored. Endothelial levels of miR-98 were significantly altered following ischemia/reperfusion insults, both in vivo and in vitro, transient middle cerebral artery occlusion (tMCAO), and oxygen–glucose deprivation (OGD), respectively. Overexpression of miR-98 reduced the mouse’s infarct size after tMCAO. Further, miR-98 lessened infiltration of proinflammatory Ly6CHI leukocytes into the brain following stroke and diminished the prevalence of M1 (activated) microglia within the impacted area. miR-98 attenuated BBB permeability, as demonstrated by changes to fluorescently-labeled dextran penetration in vivo and improved transendothelial electrical resistance (TEER) in vitro. Treatment with miR-98 improved significantly the locomotor impairment. Our study provides identification and functional assessment of miRNAs in brain endothelium and lays the groundwork for improving therapeutic approaches for patients suffering from ischemic attacks.
{"title":"miR-98 reduces endothelial dysfunction by protecting blood–brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model","authors":"David L Bernstein, Viviana Zuluaga-Ramirez, Sachin Gajghate, N. Reichenbach, B. Polyak, Y. Persidsky, Slava Rom","doi":"10.1177/0271678X19882264","DOIUrl":"https://doi.org/10.1177/0271678X19882264","url":null,"abstract":"Most neurological diseases, including stroke, lead to some degree of blood–brain barrier (BBB) dysfunction. A significant portion of BBB injury is caused by inflammation, due to pro-inflammatory factors produced in the brain, and by leukocyte engagement of the brain endothelium. Recently, microRNAs (miRNAs) have appeared as major regulators of inflammation-induced changes to gene expression in the microvascular endothelial cells (BMVEC) that comprise the BBB. However, miRNAs’ role during cerebral ischemia/reperfusion is still underexplored. Endothelial levels of miR-98 were significantly altered following ischemia/reperfusion insults, both in vivo and in vitro, transient middle cerebral artery occlusion (tMCAO), and oxygen–glucose deprivation (OGD), respectively. Overexpression of miR-98 reduced the mouse’s infarct size after tMCAO. Further, miR-98 lessened infiltration of proinflammatory Ly6CHI leukocytes into the brain following stroke and diminished the prevalence of M1 (activated) microglia within the impacted area. miR-98 attenuated BBB permeability, as demonstrated by changes to fluorescently-labeled dextran penetration in vivo and improved transendothelial electrical resistance (TEER) in vitro. Treatment with miR-98 improved significantly the locomotor impairment. Our study provides identification and functional assessment of miRNAs in brain endothelium and lays the groundwork for improving therapeutic approaches for patients suffering from ischemic attacks.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"10 1","pages":"1953 - 1965"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91026980","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 : 2020-10-01DOI: 10.1177/0271678X19882780
Patricia M. Washington, Changhee Lee, M. K. Dwyer, E. Konofagou, S. Kernie, B. Morrison
Cerebral edema and the subsequent increased intracranial pressure are associated with mortality and poor outcome following traumatic brain injury. Previous in vitro studies have shown that the Gibbs-Donnan effect, which describes the tendency of a porous, negatively charged matrix to attract positive ions and water, applies to brain tissue and that enzymatic reduction of the fixed charge density can prevent tissue swelling. We tested whether hyaluronidase, an enzyme that degrades the large, negatively charged glycosaminoglycan hyaluronan, could reduce brain edema after traumatic brain injury. In vivo, intracerebroventricular injection of hyaluronidase after controlled cortical impact in mice reduced edema in the ipsilateral hippocampus at 24 h by both the wet-weight/dry-weight method (78.15 ± 0.65% vs. 80.4 ± 0.46%; p < 0.01) and T2-weighted magnetic resonance imaging (13.88 ± 3.09% vs. 29.23 ± 6.14%; p < 0.01). Hyaluronidase did not adversely affect blood–brain-barrier-integrity measured by dynamic contrast-enhanced magnetic resonance imaging, nor did hyaluronidase negatively affect functional recovery after controlled cortical impact measured with the rotarod or Morris water maze tasks. Reduction of fixed charge density by hyaluronidase was confirmed in cortical explants in vitro (5.46 ± 1.15 µg/mg vs. 7.76 ± 1.87 µg/mg; p < 0.05). These data demonstrate that targeting the fixed charge density with hyaluronidase reduced edema in an in vivo mouse model of traumatic brain injury.
脑水肿和颅内压升高与创伤性脑损伤后的死亡率和预后不良有关。先前的体外研究表明，吉布斯-多南效应(Gibbs-Donnan effect)适用于脑组织，而酶降低固定电荷密度可以防止组织肿胀。吉布斯-多南效应描述了多孔、带负电荷的基质吸引正离子和水的趋势。我们测试了透明质酸酶，一种降解大的带负电荷的糖胺聚糖透明质酸的酶，是否可以减少创伤性脑损伤后的脑水肿。在体内，通过湿重/干重法，小鼠在控制性皮质冲击后脑室内注射透明质酸酶可减少同侧海马24小时的水肿(78.15±0.65% vs. 80.4±0.46%;p < 0.01)和t2加权磁共振成像(13.88±3.09%∶29.23±6.14%;p < 0.01)。透明质酸酶对动态增强磁共振成像测量的血脑屏障完整性没有负面影响，也没有负面影响通过旋转杆或莫里斯水迷宫任务测量的控制性皮质冲击后的功能恢复。在皮质外植体中，透明质酸酶可降低固定电荷密度(5.46±1.15µg/mg vs. 7.76±1.87µg/mg);p < 0.05)。这些数据表明，在体内创伤性脑损伤小鼠模型中，透明质酸酶靶向固定电荷密度可减少水肿。
{"title":"Hyaluronidase reduced edema after experimental traumatic brain injury","authors":"Patricia M. Washington, Changhee Lee, M. K. Dwyer, E. Konofagou, S. Kernie, B. Morrison","doi":"10.1177/0271678X19882780","DOIUrl":"https://doi.org/10.1177/0271678X19882780","url":null,"abstract":"Cerebral edema and the subsequent increased intracranial pressure are associated with mortality and poor outcome following traumatic brain injury. Previous in vitro studies have shown that the Gibbs-Donnan effect, which describes the tendency of a porous, negatively charged matrix to attract positive ions and water, applies to brain tissue and that enzymatic reduction of the fixed charge density can prevent tissue swelling. We tested whether hyaluronidase, an enzyme that degrades the large, negatively charged glycosaminoglycan hyaluronan, could reduce brain edema after traumatic brain injury. In vivo, intracerebroventricular injection of hyaluronidase after controlled cortical impact in mice reduced edema in the ipsilateral hippocampus at 24 h by both the wet-weight/dry-weight method (78.15 ± 0.65% vs. 80.4 ± 0.46%; p < 0.01) and T2-weighted magnetic resonance imaging (13.88 ± 3.09% vs. 29.23 ± 6.14%; p < 0.01). Hyaluronidase did not adversely affect blood–brain-barrier-integrity measured by dynamic contrast-enhanced magnetic resonance imaging, nor did hyaluronidase negatively affect functional recovery after controlled cortical impact measured with the rotarod or Morris water maze tasks. Reduction of fixed charge density by hyaluronidase was confirmed in cortical explants in vitro (5.46 ± 1.15 µg/mg vs. 7.76 ± 1.87 µg/mg; p < 0.05). These data demonstrate that targeting the fixed charge density with hyaluronidase reduced edema in an in vivo mouse model of traumatic brain injury.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"25 3-4","pages":"2026 - 2037"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72627745","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 : 2020-10-01DOI: 10.1177/0271678X19885124
Yaoyu Zhang, Yayan Yin, Huanjie Li, Jia-Hong Gao
Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.
{"title":"Measurement of CMRO2 and its relationship with CBF in hypoxia with an extended calibrated BOLD method","authors":"Yaoyu Zhang, Yayan Yin, Huanjie Li, Jia-Hong Gao","doi":"10.1177/0271678X19885124","DOIUrl":"https://doi.org/10.1177/0271678X19885124","url":null,"abstract":"Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) are physiological parameters that not only reflect brain health and disease but also jointly contribute to blood oxygen level-dependent (BOLD) signals. Nevertheless, unsolved issues remain concerning the CBF–CMRO2 relationship in the working brain under various oxygen conditions. In particular, the CMRO2 responses to functional tasks in hypoxia are less studied. We extended the calibrated BOLD model to incorporate CMRO2 measurements in hypoxia. The extended model, which was cross-validated with a multicompartment BOLD model, considers the influences of the reduced arterial saturation level and increased baseline cerebral blood volume (CBV) and deoxyhemoglobin concentration on the changes of BOLD signals in hypoxia. By implementing a pulse sequence to simultaneously acquire the CBV-, CBF- and BOLD-weighted signals, we investigated the effects of mild hypoxia on the CBF and CMRO2 responses to graded visual stimuli. Compared with normoxia, mild hypoxia caused significant alterations in both the amplitude and the trend of the CMRO2 responses but did not impact the corresponding CBF responses. Our observations suggested that the flow-metabolism coupling strategies in the brain during mild hypoxia were different from those during normoxia.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":"38 1","pages":"2066 - 2080"},"PeriodicalIF":0.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79842963","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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