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maiken nedergaard

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https://www.readbyqxmd.com/read/28336567/sox9-is-an-astrocyte-specific-nuclear-marker-in-the-adult-brain-outside-the-neurogenic-regions
#1
Wei Sun, Adam Cornwell, Jiashu Li, Sisi Peng, M Joana Osorio, Nadia Aalling Su Wanga, Abdellatif Benraiss, Nanhong Lou, Steven A Goldman, Maiken Nedergaard
Astrocytes have in recent years become the focus of intense experimental interest, yet markers for their definitive identification remain both scarce and imperfect. Astrocytes may be recognized as such by their expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), glutamate transporter 1 (GLT1)quaporin-4 (AQP4)ldehyde dehydrogenase 1 family member L1 (ALDH1L1)nd other proteins. Yet these proteins may all be regulated both developmentally and functionally, restricting their utility...
March 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28323163/cerebrospinal-and-interstitial-fluid-transport-via-the-glymphatic-pathway-modeled-by-optimal-mass-transport
#2
Vadim Ratner, Yi Gao, Hedok Lee, Rena Elkin, Maiken Nedergaard, Helene Benveniste, Allen Tannenbaum
The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns...
March 18, 2017: NeuroImage
https://www.readbyqxmd.com/read/28302766/csf-clearance-in-alzheimer-disease-measured-with-dynamic-pet
#3
Mony J de Leon, Yi Li, Nobuyuki Okamura, Wai H Tsui, Les A Saint Louis, Lidia Glodzik, Ricardo S Osorio, Juan Fortea, Tracy Butler, Elizabeth Pirraglia, Silvia Fossati, Hee-Jin Kim, Roxana O Carare, Maiken Nedergaard, Helene Benveniste, Henry Rusinek
Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer's disease (AD) comes from primarily from rodent models. However, unlike rodents where predominant extra-cranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Using dynamic Positron Emission Tomography (PET) with (18)F-THK5117 a tracer for tau pathology, the ventricular CSF time activity was used as a biomarker for CSF clearance...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28210958/does-global-astrocytic-calcium-signaling-participate-in-awake-brain-state-transitions-and-neuronal-circuit-function
#4
Celia Kjaerby, Rune Rasmussen, Mie Andersen, Maiken Nedergaard
We continuously need to adapt to changing conditions within our surrounding environment, and our brain needs to quickly shift between resting and working activity states in order to allow appropriate behaviors. These global state shifts are intimately linked to the brain-wide release of the neuromodulators, noradrenaline and acetylcholine. Astrocytes have emerged as a new player participating in the regulation of brain activity, and have recently been implicated in brain state shifts. Astrocytes display global Ca(2+) signaling in response to activation of the noradrenergic system, but whether astrocytic Ca(2+) signaling is causative or correlative for shifts in brain state and neural activity patterns is not known...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28188218/focal-solute-trapping-and-global-glymphatic-pathway-impairment-in-a-murine-model-of-multiple-microinfarcts
#5
Minghuan Wang, Fengfei Ding, SaiYue Deng, Xuequn Guo, Wei Wang, Jeffrey J Iliff, Maiken Nedergaard
Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. However, the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid β and tau...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28003156/direct-comparison-of-microglial-dynamics-and-inflammatory-profile-in-photothrombotic-and-arterial-occlusion-evoked-stroke
#6
Maria L Cotrina, Nanghong Lou, Jessica Tome-Garcia, James Goldman, Maiken Nedergaard
Many focal cerebral ischemia models utilize the middle cerebral artery occlusion (MCAO) evoked by coagulation to induce ischemic damage in the cortex and mimic the pathology observed in human patients. A second, increasingly popular model, the photothrombotic stroke, uses a laser beam to irradiate the MCA after administration of a photosensitizing dye. This widely used procedure is slowly replacing the MCAO model because of the easiness of the surgical protocol and the reproducibility of the damage. However, the photochemical reaction also results in wider microvascular injury...
December 18, 2016: Neuroscience
https://www.readbyqxmd.com/read/27931262/glymphatic-distribution-of-csf-derived-apoe-into-brain-is-isoform-specific-and-suppressed-during-sleep-deprivation
#7
Thiyagaragan M Achariyar, Baoman Li, Weiguo Peng, Philip B Verghese, Yang Shi, Evan McConnell, Abdellatif Benraiss, Tristan Kasper, Wei Song, Takahiro Takana, David M Holtzman, Maiken Nedergaard, Rashid Deane
BACKGROUND: Apolipoprotein E (apoE) is a major carrier of cholesterol and essential for synaptic plasticity. In brain, it's expressed by many cells but highly expressed by the choroid plexus and the predominant apolipoprotein in cerebrospinal fluid (CSF). The role of apoE in the CSF is unclear. Recently, the glymphatic system was described as a clearance system whereby CSF and ISF (interstitial fluid) is exchanged via the peri-arterial space and convective flow of ISF clearance is mediated by aquaporin 4 (AQP4), a water channel...
December 8, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27774515/a-novel-model-of-transient-occlusion-of-the-middle-cerebral-artery-in-awake-mice
#8
Lulu Xie, Hongyi Kang, Maiken Nedergaard
BACKGROUND: Stroke is one of the leading causes of death and disability worldwide. As a consequence, several excellent rodent models have been developed to gain insight into the pathophysiology of stroke and testing the efficacy of neuroprotective interventions. However, one potential problem is that albeit roughly 80% of strokes occur in awake patients, all existing murine stroke models employ anesthesia. Moreover, epidemiological studies have shown that stroke injury is more severe in the minority of patients that suffer stroke while asleep...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27586142/nkcc1-up-regulation-contributes-to-early-post-traumatic-seizures-and-increased-post-traumatic-seizure-susceptibility
#9
Fushun Wang, Xiaowei Wang, Lee A Shapiro, Maria L Cotrina, Weimin Liu, Ernest W Wang, Simeng Gu, Wei Wang, Xiaosheng He, Maiken Nedergaard, Jason H Huang
Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures...
September 1, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27499087/erythrocytes-are-oxygen-sensing-regulators-of-the-cerebral-microcirculation
#10
Helen Shinru Wei, Hongyi Kang, Izad-Yar Daniel Rasheed, Sitong Zhou, Nanhong Lou, Anna Gershteyn, Evan Daniel McConnell, Yixuan Wang, Kristopher Emil Richardson, Andre Francis Palmer, Chris Xu, Jiandi Wan, Maiken Nedergaard
Energy production in the brain depends almost exclusively on oxidative metabolism. Neurons have small energy reserves and require a continuous supply of oxygen (O2). It is therefore not surprising that one of the hallmarks of normal brain function is the tight coupling between cerebral blood flow and neuronal activity. Since capillaries are embedded in the O2-consuming neuropil, we have here examined whether activity-dependent dips in O2 tension drive capillary hyperemia. In vivo analyses showed that transient dips in tissue O2 tension elicit capillary hyperemia...
August 17, 2016: Neuron
https://www.readbyqxmd.com/read/27457281/sulforhodamine-101-a-widely-used-astrocyte-marker-can-induce-cortical-seizure-like-activity-at-concentrations-commonly-used
#11
Rune Rasmussen, Maiken Nedergaard, Nicolas Caesar Petersen
Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in both anaesthetized and awake mouse sensori-motor cortex. This cortical seizure-like activity develops in less than ten minutes following topical loading, and when applied longer, these neuronal discharges reliably evoke contra-lateral hindlimb muscle contractions...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27377722/the-homeostatic-astroglia-emerges-from-evolutionary-specialization-of-neural-cells
#12
REVIEW
Alexei Verkhratsky, Maiken Nedergaard
Evolution of the nervous system progressed through cellular diversification and specialization of functions. Conceptually, the nervous system is composed from electrically excitable neuronal networks connected with chemical synapses and non-excitable glial cells that provide for homeostasis and defence. Astrocytes are integrated into neural networks through multipartite synapses; astroglial perisynaptic processes closely enwrap synaptic contacts and control homeostasis of the synaptic cleft, supply neurons with glutamate and GABA obligatory precursor glutamine and contribute to synaptic plasticity, learning and memory...
August 5, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27343858/acupuncture-induced-analgesia-a-neurobiological-basis-in-purinergic-signaling
#13
Yong Tang, Hai-Yan Yin, Patrizia Rubini, Peter Illes
Chronic pain is a debilitating and rather common health problem. The present shortage in analgesic drugs with a favorable spectrum but without remarkable side effects furthered the search for alternative therapeutic manipulations. Increasing evidence from both basic and clinical research on acupuncture, a main alternative therapy of traditional Chinese medicine, suggests that chronic pain is sensitive to acupuncture procedures. Clarification of the underlying mechanisms is a challenge of great theoretical and practical significance...
June 25, 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/27306755/impairment-of-the-glymphatic-system-after-diabetes
#14
Quan Jiang, Li Zhang, Guangliang Ding, Esmaeil Davoodi-Bojd, Qingjiang Li, Lian Li, Neema Sadry, Maiken Nedergaard, Michael Chopp, Zhenggang Zhang
The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats...
January 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27273432/human-glia-can-both-induce-and-rescue-aspects-of-disease-phenotype-in-huntington-disease
#15
Abdellatif Benraiss, Su Wang, Stephanie Herrlinger, Xiaojie Li, Devin Chandler-Militello, Joseph Mauceri, Hayley B Burm, Michael Toner, Mikhail Osipovitch, Qiwu Jim Xu, Fengfei Ding, Fushun Wang, Ning Kang, Jian Kang, Paul C Curtin, Daniela Brunner, Martha S Windrem, Ignacio Munoz-Sanjuan, Maiken Nedergaard, Steven A Goldman
The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable...
June 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27234656/suppression-of-glymphatic-fluid-transport-in-a-mouse-model-of-alzheimer-s-disease
#16
Weiguo Peng, Thiyagarajan M Achariyar, Baoman Li, Yonghong Liao, Humberto Mestre, Emi Hitomi, Sean Regan, Tristan Kasper, Sisi Peng, Fengfei Ding, Helene Benveniste, Maiken Nedergaard, Rashid Deane
Glymphatic transport, defined as cerebrospinal fluid (CSF) peri-arterial inflow into brain, and interstitial fluid (ISF) clearance, is reduced in the aging brain. However, it is unclear whether glymphatic transport affects the distribution of soluble Aβ in Alzheimer's disease (AD). In wild type mice, we show that Aβ40 (fluorescently labeled Aβ40 or unlabeled Aβ40), was distributed from CSF to brain, via the peri-arterial space, and associated with neurons. In contrast, Aβ42 was mostly restricted to the peri-arterial space due mainly to its greater propensity to oligomerize when compared to Aβ40...
September 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27126038/changes-in-the-composition-of-brain-interstitial-ions-control-the-sleep-wake-cycle
#17
Fengfei Ding, John O'Donnell, Qiwu Xu, Ning Kang, Nanna Goldman, Maiken Nedergaard
Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K(+) concentration ([K(+)]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K(+)]e concomitant with decreases in [Ca(2+)]e, [Mg(2+)]e, [H(+)]e, and the extracellular volume...
April 29, 2016: Science
https://www.readbyqxmd.com/read/27066643/brain-drain
#18
Maiken Nedergaard, Steven A Goldman
No abstract text is available yet for this article.
March 2016: Scientific American
https://www.readbyqxmd.com/read/26877579/optimal-mass-transfer-based-estimation-of-glymphatic-transport-in-living-brain
#19
Vadim Ratner, Liangjia Zhu, Ivan Kolesov, Maiken Nedergaard, Helene Benveniste, Allen Tannenbaum
It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the 'glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs(1,2). It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through para-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns...
February 21, 2015: Proceedings of SPIE
https://www.readbyqxmd.com/read/26690495/ultra-fast-magnetic-resonance-encephalography-of-physiological-brain-activity-glymphatic-pulsation-mechanisms
#20
Vesa Kiviniemi, Xindi Wang, Vesa Korhonen, Tuija Keinänen, Timo Tuovinen, Joonas Autio, Pierre LeVan, Shella Keilholz, Yu-Feng Zang, Jürgen Hennig, Maiken Nedergaard
The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations...
June 2016: Journal of Cerebral Blood Flow and Metabolism
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