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maiken nedergaard

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
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
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
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
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
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...
June 15, 2016: Journal of Cerebral Blood Flow and Metabolism
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...
2016: Nature Communications
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
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
Maiken Nedergaard, Steven A Goldman
No abstract text is available yet for this article.
March 2016: Scientific American
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
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
Evan D McConnell, Helen S Wei, Katherine M Reitz, Hongyi Kang, Takahiro Takano, G Edward Vates, Maiken Nedergaard
Aneurysmal subarachnoid hemorrhage remains one of the more devastating forms of stroke due in large part to delayed cerebral ischemia that appears days to weeks following the initial hemorrhage. Therapies exclusively targeting large caliber arterial vasospasm have fallen short, and thus we asked whether capillary dysfunction contributes to delayed cerebral ischemia after subarachnoid hemorrhage. Using a mouse model of subarachnoid hemorrhage and two-photon microscopy we showed capillary dysfunction unrelated to upstream arterial constriction...
September 2016: Journal of Cerebral Blood Flow and Metabolism
John O'Donnell, Fengfei Ding, Maiken Nedergaard
Astrocytes are the chief supportive cells in the central nervous system, but work over the past 20 years have documented that astrocytes also contribute to complex neural processes, such as working memory. Recent discoveries of norepinephrine-mediated astrocytic Ca(2+) responses have raised the possibility that astrocytic activity in the adult brain is driven by global responses to changes in behavioral state. Moreover, analysis of the interstitial space volume suggests that astrocytes may undergo changes in cell volume in response to activation of norepinephrine receptors...
March 2015: Current Sleep Medicine Reports
Jeffrey J Iliff, Steven A Goldman, Maiken Nedergaard
No abstract text is available yet for this article.
October 2015: Lancet Neurology
Anna L Ribeiro Xavier, Benjamin T Kress, Steven A Goldman, João R Lacerda de Menezes, Maiken Nedergaard
UNLABELLED: Microglia are involved in synaptic pruning both in development and in the mature CNS. In this study, we investigated whether microglia might further contribute to circuit plasticity by modulating neuronal recruitment from the neurogenic subventricular zone (SVZ) of the adult mouse striatum. We found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low expression of purinoceptors and lack of ATP-elicitable chemotaxis...
August 26, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hedok Lee, Lulu Xie, Mei Yu, Hongyi Kang, Tian Feng, Rashid Deane, Jean Logan, Maiken Nedergaard, Helene Benveniste
UNLABELLED: The glymphatic pathway expedites clearance of waste, including soluble amyloid β (Aβ) from the brain. Transport through this pathway is controlled by the brain's arousal level because, during sleep or anesthesia, the brain's interstitial space volume expands (compared with wakefulness), resulting in faster waste removal. Humans, as well as animals, exhibit different body postures during sleep, which may also affect waste removal. Therefore, not only the level of consciousness, but also body posture, might affect CSF-interstitial fluid (ISF) exchange efficiency...
August 5, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Helene Benveniste, Patrick R Hof, Maiken Nedergaard, Karl Bechter
No abstract text is available yet for this article.
September 1, 2015: Journal of Comparative Neurology
Rany Makaryus, Hedok Lee, Tian Feng, June-Hee Park, Maiken Nedergaard, Zvi Jacob, Grigori Enikolopov, Helene Benveniste
BACKGROUND: A wealth of data shows neuronal demise after general anesthesia in the very young rodent brain. Herein, the authors apply proton magnetic resonance spectroscopy (1HMRS), testing the hypothesis that neurotoxic exposure during peak synaptogenesis can be tracked via changes in neuronal metabolites. METHODS: 1HMRS spectra were acquired in the brain (thalamus) of neonatal rat pups 24 and 48 h after sevoflurane exposure on postnatal day (PND) 7 and 15 and in unexposed, sham controls...
September 2015: Anesthesiology
Steven A Goldman, Maiken Nedergaard, Martha S Windrem
As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well...
August 2015: Glia
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