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":null,"pages":null},"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: 10.1177/0271678X19861448
Guang-Huar Young, Sung-Chun Tang, Vincent Wu, Kuo-Chuan Wang, Jing-Yi Nong, Po-Yuan Huang, Chaur-Jong Hu, H. Chiou, J. Jeng, C. Hsu
Our study aimed to establish the role of hemojuvelin (HJV) in acute ischemic stroke (AIS). We performed immunohistochemistry for HJV expression in human brain tissues from 10 AIS and 2 non-stroke autopsy subjects. Plasma HJV was measured in 112 AIS patients within 48 h after stroke. The results showed significantly increased HJV expression in brain tissues from AIS patients compare to non-stroke subjects. After adjusting for clinical variables, plasma levels of HJV within 48 h after stroke were an independent predictor of poor functional outcome three months post-stroke (OR:1.78, 95% CI: 1.03–3.07; P = 0.038). In basic part, Western blotting showed that HJV expression in mice brains was apparent at 3 h after middle cerebral artery occlusion (MCAO), and increased significantly at 72 h. In cultured cortical neurons, expression of HJV protein increased remarkably 24 h after oxygen glucose deprivation (OGD), and small interfering RNAs (siHJV) transfected OGD neurons had a lower apoptotic rate. Importantly, 72 h post-MCAO, HJV knockout mice had significantly smaller infarcts and less expression of cleaved caspase-3 protein compared with wild-type mice. In summary, HJV participates in the mechanisms of post-stroke neuronal injury, and that plasma HJV levels can be a potential early outcome indicator for AIS patients.
{"title":"The functional role of hemojuvelin in acute ischemic stroke","authors":"Guang-Huar Young, Sung-Chun Tang, Vincent Wu, Kuo-Chuan Wang, Jing-Yi Nong, Po-Yuan Huang, Chaur-Jong Hu, H. Chiou, J. Jeng, C. Hsu","doi":"10.1177/0271678X19861448","DOIUrl":"https://doi.org/10.1177/0271678X19861448","url":null,"abstract":"Our study aimed to establish the role of hemojuvelin (HJV) in acute ischemic stroke (AIS). We performed immunohistochemistry for HJV expression in human brain tissues from 10 AIS and 2 non-stroke autopsy subjects. Plasma HJV was measured in 112 AIS patients within 48 h after stroke. The results showed significantly increased HJV expression in brain tissues from AIS patients compare to non-stroke subjects. After adjusting for clinical variables, plasma levels of HJV within 48 h after stroke were an independent predictor of poor functional outcome three months post-stroke (OR:1.78, 95% CI: 1.03–3.07; P = 0.038). In basic part, Western blotting showed that HJV expression in mice brains was apparent at 3 h after middle cerebral artery occlusion (MCAO), and increased significantly at 72 h. In cultured cortical neurons, expression of HJV protein increased remarkably 24 h after oxygen glucose deprivation (OGD), and small interfering RNAs (siHJV) transfected OGD neurons had a lower apoptotic rate. Importantly, 72 h post-MCAO, HJV knockout mice had significantly smaller infarcts and less expression of cleaved caspase-3 protein compared with wild-type mice. In summary, HJV participates in the mechanisms of post-stroke neuronal injury, and that plasma HJV levels can be a potential early outcome indicator for AIS patients.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91020685","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":null,"pages":null},"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}
Pub Date : 2020-04-01Epub Date: 2019-11-13DOI: 10.1177/0271678X19888630
Rongrong Wang, Yaan Liu, Qing Ye, Sulaiman H Hassan, Jingyan Zhao, Sicheng Li, Xiaoming Hu, Rehana K Leak, Marcelo Rocha, Lawrence R Wechsler, Jun Chen, Yejie Shi
{"title":"RNA sequencing reveals novel macrophage transcriptome favoring neurovascular plasticity after ischemic stroke.","authors":"Rongrong Wang, Yaan Liu, Qing Ye, Sulaiman H Hassan, Jingyan Zhao, Sicheng Li, Xiaoming Hu, Rehana K Leak, Marcelo Rocha, Lawrence R Wechsler, Jun Chen, Yejie Shi","doi":"10.1177/0271678X19888630","DOIUrl":"10.1177/0271678X19888630","url":null,"abstract":"","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84131403","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 : 2019-12-02DOI: 10.1177/0271678X19892660
A. Pandey, B. Daou, N. Chaudhary, G. Xi
Intracerebral hemorrhage is associated with significant morbidity and mortality. Some clinical trials demonstrated a trend towards benefit with surgical evacuation of intracerebral hemorrhage, without strong statistically significant results. Subsequent studies focused on minimally invasive techniques. Improved outcomes were more likely with surgical reduction of intracerebral hemorrhage volume to ≤15 mL. Deferoxamine is currently being evaluated as a therapeutic tool in intracerebral hemorrhage with promising results. There continues to be a lack of level I evidence supporting medical and surgical tools for intracerebral hemorrhage evacuation. Could a combination of minimally invasive surgery with hematoma lysis and Deferoxamine result in more effective hematoma evacuation?
{"title":"A combination of Deferoxamine mesylate and minimally invasive surgery with hematoma lysis for evacuation of intracerebral hemorrhage","authors":"A. Pandey, B. Daou, N. Chaudhary, G. Xi","doi":"10.1177/0271678X19892660","DOIUrl":"https://doi.org/10.1177/0271678X19892660","url":null,"abstract":"Intracerebral hemorrhage is associated with significant morbidity and mortality. Some clinical trials demonstrated a trend towards benefit with surgical evacuation of intracerebral hemorrhage, without strong statistically significant results. Subsequent studies focused on minimally invasive techniques. Improved outcomes were more likely with surgical reduction of intracerebral hemorrhage volume to ≤15 mL. Deferoxamine is currently being evaluated as a therapeutic tool in intracerebral hemorrhage with promising results. There continues to be a lack of level I evidence supporting medical and surgical tools for intracerebral hemorrhage evacuation. Could a combination of minimally invasive surgery with hematoma lysis and Deferoxamine result in more effective hematoma evacuation?","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81994205","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 : 2019-11-27DOI: 10.1177/0271678X19891359
Alexander Ruesch, Samantha E. Schmitt, Jason Yang, Matthew A. Smith, J. Kainerstorfer
Intracranial pressure (ICP) is typically measured invasively through a sensor placed inside the brain or a needle inserted into the spinal canal, limiting the patient population on which this assessment can be performed. Currently, non-invasive methods are limited due to lack of sensitivity and thus only apply to extreme cases of increased ICP, instead of use in general clinical practice. We demonstrate a novel application for near-infrared spectroscopy (NIRS) to accurately estimate ICP changes over time. Using a non-human primate (Rhesus Macaque) model, we collected optical data while we induced ICP oscillations at multiple ICP levels obtained by manipulating the height of a fluid column connected via a catheter to the lateral ventricle. Hemodynamic responses to ICP changes were measured at the occipital pole and compared to changes detected by a conventional intraparenchymal ICP probe. We demonstrate that hemoglobin concentrations are highly correlated with induced ICP oscillations and that this response is frequency dependent. We translated the NIRS data into non-invasive ICP measurements via a fitted non-parametric transfer function, demonstrating a match in both magnitude and time alignment with an invasively measured reference. Our results demonstrate that NIRS has the potential for non-invasive ICP monitoring.
{"title":"Fluctuations in intracranial pressure can be estimated non-invasively using near-infrared spectroscopy in non-human primates","authors":"Alexander Ruesch, Samantha E. Schmitt, Jason Yang, Matthew A. Smith, J. Kainerstorfer","doi":"10.1177/0271678X19891359","DOIUrl":"https://doi.org/10.1177/0271678X19891359","url":null,"abstract":"Intracranial pressure (ICP) is typically measured invasively through a sensor placed inside the brain or a needle inserted into the spinal canal, limiting the patient population on which this assessment can be performed. Currently, non-invasive methods are limited due to lack of sensitivity and thus only apply to extreme cases of increased ICP, instead of use in general clinical practice. We demonstrate a novel application for near-infrared spectroscopy (NIRS) to accurately estimate ICP changes over time. Using a non-human primate (Rhesus Macaque) model, we collected optical data while we induced ICP oscillations at multiple ICP levels obtained by manipulating the height of a fluid column connected via a catheter to the lateral ventricle. Hemodynamic responses to ICP changes were measured at the occipital pole and compared to changes detected by a conventional intraparenchymal ICP probe. We demonstrate that hemoglobin concentrations are highly correlated with induced ICP oscillations and that this response is frequency dependent. We translated the NIRS data into non-invasive ICP measurements via a fitted non-parametric transfer function, demonstrating a match in both magnitude and time alignment with an invasively measured reference. Our results demonstrate that NIRS has the potential for non-invasive ICP monitoring.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88400520","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 : 2019-11-25DOI: 10.1177/0271678X19890931
Qiang Zhao, T. Yan, M. Chopp, P. Venkat, Jieli Chen
Stroke is a leading cause of mortality and morbidity, with long-term debilitating effects. Accumulating evidence from experimental studies as well as observational studies in patients suggests a cross talk between the brain and kidney after stroke. Stroke may lead to kidney dysfunction which can adversely impact patient outcome. In this review article, we discuss the epidemiology and mechanisms of brain–kidney interaction following ischemic stroke. Specifically, we discuss the role of the central autonomic network, autoregulation, inflammatory and immune responses, the role of extracellular vesicles and their cargo microRNA, in mediating brain–kidney interaction following stroke. Understanding the bidirectional nature of interaction between the brain and kidney after cerebral injury would have clinical implications for the treatment of stroke and overall patient outcome.
{"title":"Brain–kidney interaction: Renal dysfunction following ischemic stroke","authors":"Qiang Zhao, T. Yan, M. Chopp, P. Venkat, Jieli Chen","doi":"10.1177/0271678X19890931","DOIUrl":"https://doi.org/10.1177/0271678X19890931","url":null,"abstract":"Stroke is a leading cause of mortality and morbidity, with long-term debilitating effects. Accumulating evidence from experimental studies as well as observational studies in patients suggests a cross talk between the brain and kidney after stroke. Stroke may lead to kidney dysfunction which can adversely impact patient outcome. In this review article, we discuss the epidemiology and mechanisms of brain–kidney interaction following ischemic stroke. Specifically, we discuss the role of the central autonomic network, autoregulation, inflammatory and immune responses, the role of extracellular vesicles and their cargo microRNA, in mediating brain–kidney interaction following stroke. Understanding the bidirectional nature of interaction between the brain and kidney after cerebral injury would have clinical implications for the treatment of stroke and overall patient outcome.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74170077","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 : 2019-11-23DOI: 10.1177/0271678X19890830
P. Sharp, K. Ameen-Ali, L. Boorman, S. Harris, S. Wharton, C. Howarth, O. Shabir, P. Redgrave, J. Berwick
Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer’s disease (AD), which could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime to allow repeated measurements of neurovascular function over three months in the J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9–12 months old at the start of the experiment. Mice were chronically prepared with a cranial window through which 2-Dimensional optical imaging spectroscopy (2D-OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and 2D-OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.
{"title":"Neurovascular coupling preserved in a chronic mouse model of Alzheimer’s disease: Methodology is critical","authors":"P. Sharp, K. Ameen-Ali, L. Boorman, S. Harris, S. Wharton, C. Howarth, O. Shabir, P. Redgrave, J. Berwick","doi":"10.1177/0271678X19890830","DOIUrl":"https://doi.org/10.1177/0271678X19890830","url":null,"abstract":"Impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer’s disease (AD), which could serve as an early biomarker of cerebral pathology. We have established an anaesthetic regime to allow repeated measurements of neurovascular function over three months in the J20 mouse model of AD (J20-AD) and wild-type (WT) controls. Animals were 9–12 months old at the start of the experiment. Mice were chronically prepared with a cranial window through which 2-Dimensional optical imaging spectroscopy (2D-OIS) was used to generate functional maps of the cerebral blood volume and saturation changes evoked by whisker stimulation and vascular reactivity challenges. Unexpectedly, the hemodynamic responses were largely preserved in the J20-AD group. This result failed to confirm previous investigations using the J20-AD model. However, a final acute electrophysiology and 2D-OIS experiment was performed to measure both neural and hemodynamic responses concurrently. In this experiment, previously reported deficits in neurovascular coupling in the J20-AD model were observed. This suggests that J20-AD mice may be more susceptible to the physiologically stressing conditions of an acute experimental procedure compared to WT animals. These results therefore highlight the importance of experimental procedure when determining the characteristics of animal models of human disease.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73907388","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 : 2019-11-21DOI: 10.1177/0271678X19889089
Brittany A. Matenchuk, M. James, Rachel J. Skow, Paige K Wakefield, Christina M. MacKay, C. Steinback, Margie H. Davenport
Cerebrovascular adaptation to pregnancy is poorly understood. We sought to assess cerebrovascular regulation in response to visual stimulation, hypercapnia and exercise across the three trimesters of pregnancy. Using transcranial Doppler (TCD) ultrasound, middle and posterior cerebral artery mean blood velocities (MCAvmean and PCAvmean) were measured continuously at rest and in response to (1) visual stimulation to assess neurovascular coupling (NVC); (2) a modified Duffin hyperoxic CO2 rebreathe test, and (3) an incremental cycling exercise test to volitional fatigue in non-pregnant (n = 26; NP) and pregnant women (first trimester [n = 13; TM1], second trimester [n = 21; TM2], and third trimester [n = 20; TM3]) in total 47 women. At rest, MCAvmean and PETCO2 were lower in TM2 compared to NP. PCAvmean was lower in TM2 but not TM1 or TM3 compared to NP. Cerebrovascular reactivity in MCAvmean and PCAvmean during the hypercapnic rebreathing test was not different between pregnant and non-pregnant women. MCAvmean continued to increase over the second half of the exercise test in TM2 and TM3, while it decreased in NP due to differences in ΔPETCO2 between groups. Pregnant women experienced a delayed decrease in MCAvmean in response to maximal exercise compared to non-pregnant controls which was explained by CO2 reactivity and PETCO2 level.
{"title":"Longitudinal study of cerebral blood flow regulation during exercise in pregnancy","authors":"Brittany A. Matenchuk, M. James, Rachel J. Skow, Paige K Wakefield, Christina M. MacKay, C. Steinback, Margie H. Davenport","doi":"10.1177/0271678X19889089","DOIUrl":"https://doi.org/10.1177/0271678X19889089","url":null,"abstract":"Cerebrovascular adaptation to pregnancy is poorly understood. We sought to assess cerebrovascular regulation in response to visual stimulation, hypercapnia and exercise across the three trimesters of pregnancy. Using transcranial Doppler (TCD) ultrasound, middle and posterior cerebral artery mean blood velocities (MCAvmean and PCAvmean) were measured continuously at rest and in response to (1) visual stimulation to assess neurovascular coupling (NVC); (2) a modified Duffin hyperoxic CO2 rebreathe test, and (3) an incremental cycling exercise test to volitional fatigue in non-pregnant (n = 26; NP) and pregnant women (first trimester [n = 13; TM1], second trimester [n = 21; TM2], and third trimester [n = 20; TM3]) in total 47 women. At rest, MCAvmean and PETCO2 were lower in TM2 compared to NP. PCAvmean was lower in TM2 but not TM1 or TM3 compared to NP. Cerebrovascular reactivity in MCAvmean and PCAvmean during the hypercapnic rebreathing test was not different between pregnant and non-pregnant women. MCAvmean continued to increase over the second half of the exercise test in TM2 and TM3, while it decreased in NP due to differences in ΔPETCO2 between groups. Pregnant women experienced a delayed decrease in MCAvmean in response to maximal exercise compared to non-pregnant controls which was explained by CO2 reactivity and PETCO2 level.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81404403","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 : 2019-11-20DOI: 10.1177/0271678X19888967
F. De Guio, M. Duering, F. Fazekas, F. de Leeuw, S. Greenberg, L. Pantoni, Agnès Aghetti, Eric E. Smith, J. Wardlaw, E. Jouvent
Brain atrophy is increasingly evaluated in cerebral small vessel diseases. We aim at systematically reviewing the available data regarding its extent, correlates and cognitive consequences. Given that in this context, brain atrophy measures might be biased, the first part of the review focuses on technical aspects. Thereafter, data from the literature are analyzed in light of these potential limitations, to better understand the relationships between brain atrophy and other MRI markers of cerebral small vessel diseases. In the last part, we review the links between brain atrophy and cognitive alterations in patients with cerebral small vessel diseases.
{"title":"Brain atrophy in cerebral small vessel diseases: Extent, consequences, technical limitations and perspectives: The HARNESS initiative","authors":"F. De Guio, M. Duering, F. Fazekas, F. de Leeuw, S. Greenberg, L. Pantoni, Agnès Aghetti, Eric E. Smith, J. Wardlaw, E. Jouvent","doi":"10.1177/0271678X19888967","DOIUrl":"https://doi.org/10.1177/0271678X19888967","url":null,"abstract":"Brain atrophy is increasingly evaluated in cerebral small vessel diseases. We aim at systematically reviewing the available data regarding its extent, correlates and cognitive consequences. Given that in this context, brain atrophy measures might be biased, the first part of the review focuses on technical aspects. Thereafter, data from the literature are analyzed in light of these potential limitations, to better understand the relationships between brain atrophy and other MRI markers of cerebral small vessel diseases. In the last part, we review the links between brain atrophy and cognitive alterations in patients with cerebral small vessel diseases.","PeriodicalId":15356,"journal":{"name":"Journal of Cerebral Blood Flow & Metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72877061","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}