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Author Harald Sontheimer

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Using Zebrafish to Elucidate Glial-Vascular Interactions During CNS Development.

Robyn A Umans, Carolyn Pollock, William A Mills, Kareem C Clark, Y Albert Pan, Harald Sontheimer,

An emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied <i>in vivo</i> and great strides have been made using mice to longitudinally image glial-vascular ... Read more >>

Front Cell Dev Biol (Frontiers in cell and developmental biology)
[2021, 9:654338]

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Astrocyte plasticity ensures continued endfoot coverage of cerebral blood vessels and integrity of the blood brain barrier, with plasticity declining with normal aging

William Mills, Shan Jiang, Joelle Martin, AnnaLin Woo, Matthew Bergstresser, Ian Kimbrough, Harald Sontheimer,

Astrocytes extend endfeet that enwrap the vasculature. Disruptions to this association in disease coincide with breaches in blood-brain barrier (BBB) integrity, so we asked if the focal ablation of an astrocyte is sufficient to disrupt the BBB. 2Phatal ablation of astrocytes induced a plasticity response whereby surrounding astrocytes extended processes ... Read more >>

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Antiepileptogenesis and disease modification: Progress, challenges, and the path forward-Report of the Preclinical Working Group of the 2018 NINDS-sponsored antiepileptogenesis and disease modification workshop.

Aristea S Galanopoulou, Wolfgang Löscher, Laura Lubbers, Terence J O'Brien, Kevin Staley, Annamaria Vezzani, Raimondo D'Ambrosio, H Steve White, Harald Sontheimer, John A Wolf, Roy Twyman, Vicky Whittemore, Karen S Wilcox, Brian Klein,

Epilepsy is one of the most common chronic brain diseases and is often associated with cognitive, behavioral, or other medical conditions. The need for therapies that would prevent, ameliorate, or cure epilepsy and the attendant comorbidities is a priority for both epilepsy research and public health. In 2018, the National ... Read more >>

Epilepsia Open (Epilepsia open)
[2021, 6(2):276-296]

Cited: 1 time

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Dysregulation of Ambient Glutamate and Glutamate Receptors in Epilepsy: An Astrocytic Perspective.

Oscar B Alcoreza, Dipan C Patel, Bhanu P Tewari, Harald Sontheimer,

Given the important functions that glutamate serves in excitatory neurotransmission, understanding the regulation of glutamate in physiological and pathological states is critical to devising novel therapies to treat epilepsy. Exclusive expression of pyruvate carboxylase and glutamine synthetase in astrocytes positions astrocytes as essential regulators of glutamate in the central nervous ... Read more >>

Front Neurol (Frontiers in neurology)
[2021, 12:652159]

Cited: 1 time

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Neuroscience: The New English Major?

Kristin F Phillips, Harald Sontheimer,

Once strictly the domain of medical and graduate education, neuroscience has made its way into the undergraduate curriculum with over 230 colleges and universities now offering a bachelor's degree in neuroscience. The disciplinary focus on the brain teaches students to apply science to the understanding of human behavior, human interactions, ... Read more >>

Neuroscientist (The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry)
[2021, :10738584211003992]

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Reactive astrocyte nomenclature, definitions, and future directions.

Carole Escartin, Elena Galea, András Lakatos, James P O'Callaghan, Gabor C Petzold, Alberto Serrano-Pozo, Christian Steinhäuser, Andrea Volterra, Giorgio Carmignoto, Amit Agarwal, Nicola J Allen, Alfonso Araque, Luis Barbeito, Ari Barzilai, Dwight E Bergles, Gilles Bonvento, Arthur M Butt, Wei-Ting Chen, Martine Cohen-Salmon, Colm Cunningham, Benjamin Deneen, Bart De Strooper, Blanca Díaz-Castro, Cinthia Farina, Marc Freeman, Vittorio Gallo, James E Goldman, Steven A Goldman, Magdalena Götz, Antonia Gutiérrez, Philip G Haydon, Dieter H Heiland, Elly M Hol, Matthew G Holt, Masamitsu Iino, Ksenia V Kastanenka, Helmut Kettenmann, Baljit S Khakh, Schuichi Koizumi, C Justin Lee, Shane A Liddelow, Brian A MacVicar, Pierre Magistretti, Albee Messing, Anusha Mishra, Anna V Molofsky, Keith K Murai, Christopher M Norris, Seiji Okada, Stéphane H R Oliet, João F Oliveira, Aude Panatier, Vladimir Parpura, Marcela Pekna, Milos Pekny, Luc Pellerin, Gertrudis Perea, Beatriz G Pérez-Nievas, Frank W Pfrieger, Kira E Poskanzer, Francisco J Quintana, Richard M Ransohoff, Miriam Riquelme-Perez, Stefanie Robel, Christine R Rose, Jeffrey D Rothstein, Nathalie Rouach, David H Rowitch, Alexey Semyanov, Swetlana Sirko, Harald Sontheimer, Raymond A Swanson, Javier Vitorica, Ina-Beate Wanner, Levi B Wood, Jiaqian Wu, Binhai Zheng, Eduardo R Zimmer, Robert Zorec, Michael V Sofroniew, Alexei Verkhratsky,

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear ... Read more >>

Nat Neurosci (Nature neuroscience)
[2021, 24(3):312-325]

Cited: 41 times

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Using zebrafish to elucidate glial-vascular interactions during CNS development

Robyn Umans, Carolyn Pollock, William Mills, Harald Sontheimer,

An emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied in vivo and great strides have been made using mice to longitudinally image glial-vascular ... Read more >>

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Spatially expandable fiber-based probes as a multifunctional deep brain interface.

Shan Jiang, Dipan C Patel, Jongwoon Kim, Shuo Yang, William A Mills, Yujing Zhang, Kaiwen Wang, Ziang Feng, Sujith Vijayan, Wenjun Cai, Anbo Wang, Yuanyuan Guo, Ian F Kimbrough, Harald Sontheimer, Xiaoting Jia,

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):6115]

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Spatially expandable fiber-based probes as a multifunctional deep brain interface

Shan Jiang, Dipan Patel, Jongwoon Kim, Shuo Yang, William Mills, Yujing Zhang, Kaiwen Wang, Ziang Feng, Sujith Vijayan, Wenjun Cai, Anbo Wang, Yuanyuan Guo, Ian Kimbrough, Harald Sontheimer, Xiaoting Jia,

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high ... Read more >>

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Fishing for contact: Modeling perivascular glioma invasion in the zebrafish brain

Robyn Umans, Mattie ten Kate, Carolyn Pollock, Harald Sontheimer,

Glioblastoma multiforme (GBM) is a highly invasive, central nervous system (CNS) cancer for which there is no a cure. Invading tumor cells evade treatment, limiting the efficacy of the current standard of care regimen. Understanding the underlying invasive behaviors that support tumor growth may allow for generation of novel GBM ... Read more >>

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Pericytes Directly Communicate with Emerging Endothelial Cells During Vasculogenesis

Laura Beth Payne, Bhanu Tewari, Logan Dunkenberger, Samantha Bond, Alyssa Savelli, Jordan Darden, Huaning Zhao, Michael Powell, Kenneth Oestreich, Harald Sontheimer, Sophie Dal-Pra, John Chappell,

<h4>Summary</h4> Pericytes (PCs), cells that extend along capillaries to contribute stability and other critical functions to established vasculature, are attracting attention from various fields involving vascular-related pathologies. Here, we demonstrate primary evidence of PC communication with endothelial cells (ECs) prior to tube coalescence. Observations of apparent PCs during early embryogenesis ... Read more >>

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3D bioprinting using hollow multifunctional fiber impedimetric sensors.

Alexander P Haring, Shan Jiang, Catherine Barron, Emily G Thompson, Harald Sontheimer, Jia-Qiang He, Xiaoting Jia, Blake N Johnson,

3D bioprinting is an emerging biofabrication process for the production of adherent cell-based products, including engineered tissues and foods. While process innovations are rapidly occurring in the area of process monitoring, which can improve fundamental understanding of process-structure-property relations as well as product quality by closed-loop control techniques, in-line sensing ... Read more >>

Biofabrication (Biofabrication)
[2020, 12(3):035026]

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The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients.

Aarash K Roshandel, Christopher M Busch, Jennifer Van Mullekom, Joshua A Cuoco, Cara M Rogers, Lisa S Apfel, Eric A Marvin, Harald W Sontheimer, Robyn A Umans,

Tumor protein 53 (p53) regulates fundamental pathways of cellular growth and differentiation. Aberrant p53 expression in glioblastoma multiforme, a terminal brain cancer, has been associated with worse patient outcomes and decreased chemosensitivity. Therefore, correctly identifying p53 status in glioblastoma is of great clinical significance. p53 immunohistochemistry is used to detect ... Read more >>

Oncotarget (Oncotarget)
[2019, 10(58):6204-6218]

Cited: 0 times

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Acetylcholine Receptor Activation as a Modulator of Glioblastoma Invasion.

Emily G Thompson, Harald Sontheimer,

Grade IV astrocytomas, or glioblastomas (GBMs), are the most common malignant primary brain tumor in adults. The median GBM patient survival of 12-15 months has remained stagnant, in spite of treatment strategies, making GBMs a tremendous challenge clinically. This is at least in part due to the complex interaction of ... Read more >>

Cells (Cells)
[2019, 8(10):]

Cited: 6 times

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Sulfasalazine decreases mouse cortical hyperexcitability.

Oscar Alcoreza, Bhanu P Tewari, Allison Bouslog, Andrew Savoia, Harald Sontheimer, Susan L Campbell,

<h4>Objective</h4>Currently prescribed antiepileptic drugs (AEDs) are ineffective in treating approximately 30% of epilepsy patients. Sulfasalazine (SAS) is an US Food and Drug Administration (FDA)-approved drug for the treatment of Crohn disease that has been shown to inhibit the cystine/glutamate antiporter system xc- (SXC) and decrease tumor-associated seizures. This study evaluates ... Read more >>

Epilepsia (Epilepsia)
[2019, 60(7):1365-1377]

Cited: 5 times

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Protocol to quantitatively assess the structural integrity of Perineuronal Nets ex vivo.

Bhanu P Tewari, Harald Sontheimer,

Perineuronal nets (PNNs) are extracellular matrix assemblies of highly negatively charged proteoglycans that wrap around fast-spiking parvalbumin (PV) expressing interneurons in the cerebral cortex. PNNs play important roles in neuronal plasticity and modulate biophysical properties of the enclosed interneurons. Various central nervous system diseases including schizophrenia, Alzheimer disease and epilepsy ... Read more >>

Bio Protoc (Bio-protocol)
[2019, 9(10):e3234]

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Neuron-glia interactions in the pathophysiology of epilepsy.

Dipan C Patel, Bhanu P Tewari, Lata Chaunsali, Harald Sontheimer,

Epilepsy is a neurological disorder afflicting ~65 million people worldwide. It is caused by aberrant synchronized firing of populations of neurons primarily due to imbalance between excitatory and inhibitory neurotransmission. Hence, the historical focus of epilepsy research has been neurocentric. However, the past two decades have enjoyed an explosion of ... Read more >>

Nat Rev Neurosci (Nature reviews. Neuroscience)
[2019, 20(5):282-297]

Cited: 37 times

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Process- and bio-inspired hydrogels for 3D bioprinting of soft free-standing neural and glial tissues.

Alexander P Haring, Emily G Thompson, Yuxin Tong, Sahil Laheri, Ellen Cesewski, Harald Sontheimer, Blake N Johnson,

A bio-inspired hydrogel for 3D bioprinting of soft free-standing neural tissues is presented. The novel filler-free bioinks were designed by combining natural polymers for extracellular matrix biomimicry with synthetic polymers to endow desirable rheological properties for 3D bioprinting. Crosslinking of thiolated Pluronic F-127 with dopamine-conjugated (DC) gelatin and DC hyaluronic ... Read more >>

Biofabrication (Biofabrication)
[2019, 11(2):025009]

Cited: 8 times

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Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy.

Bhanu P Tewari, Lata Chaunsali, Susan L Campbell, Dipan C Patel, Adam E Goode, Harald Sontheimer,

Brain tumor patients commonly present with epileptic seizures. We show that tumor-associated seizures are the consequence of impaired GABAergic inhibition due to an overall loss of peritumoral fast spiking interneurons (FSNs) concomitant with a significantly reduced firing rate of those that remain. The reduced firing is due to the degradation ... Read more >>

Nat Commun (Nature communications)
[2018, 9(1):4724]

Cited: 27 times

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Brain cancer: Tumour cells on neighbourhood watch.

Harald Sontheimer,

Nature (Nature)
[2015, 528(7580):49-50]

Cited: 11 times

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Combating malignant astrocytes: Strategies mitigating tumor invasion.

Robyn A Umans, Harald Sontheimer,

Malignant gliomas are glial-derived, primary brain tumors that carry poor prognosis. Existing therapeutics are largely ineffective and dramatically affect quality of life. The standard of care details a taxing combination of surgical resection, radiation of the resection cavity, and temozolomide (TMZ) chemotherapy, with treatment extending life by only an average ... Read more >>

Neurosci Res (Neuroscience research)
[2018, 126:22-30]

Cited: 5 times

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Polymer Composite with Carbon Nanofibers Aligned during Thermal Drawing as a Microelectrode for Chronic Neural Interfaces.

Yuanyuan Guo, Shan Jiang, Benjamin J B Grena, Ian F Kimbrough, Emily G Thompson, Yoel Fink, Harald Sontheimer, Tatsuo Yoshinobu, Xiaoting Jia,

Microelectrodes provide a direct pathway to investigate brain activities electrically from the external world, which has advanced our fundamental understanding of brain functions and has been utilized for rehabilitative applications as brain-machine interfaces. However, minimizing the tissue response and prolonging the functional durations of these devices remain challenging. Therefore, the ... Read more >>

ACS Nano (ACS nano)
[2017, 11(7):6574-6585]

Cited: 13 times

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Glia as drivers of abnormal neuronal activity.

Stefanie Robel, Harald Sontheimer,

Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them unable to perform important housekeeping functions. Indeed, successful surgical treatment of mesiotemporal lobe epilepsy hinges on the removal of the glial scar. New research now extends the role of astrocytes, suggesting ... Read more >>

Nat Neurosci (Nature neuroscience)
[2016, 19(1):28-33]

Cited: 73 times

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SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma.

Stephanie M Robert, Susan C Buckingham, Susan L Campbell, Stefanie Robel, Kenneth T Holt, Toyin Ogunrinu-Babarinde, Paula P Warren, David M White, Meredith A Reid, Jenny M Eschbacher, Michael E Berens, Adrienne C Lahti, Louis B Nabors, Harald Sontheimer,

Glioma is the most common malignant primary brain tumor. Its rapid growth is aided by tumor-mediated glutamate release, creating peritumoral excitotoxic cell death and vacating space for tumor expansion. Glioma glutamate release may also be responsible for seizures, which complicate the clinical course for many patients and are often the ... Read more >>

Sci Transl Med (Science translational medicine)
[2015, 7(289):289ra86]

Cited: 76 times

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A frightening thought: Neuronal activity enhances tumor growth.

Emily G Thompson, Harald Sontheimer,

Stem cells present in the adult brain are regulated by neuronal activity; malignant gliomas, which most likely originate from this population of cells, could also be regulated in this manner. A recent study by Venkatesh et al. published in Cell has identified Neuroligin-3 (NLGN3) as a mitogen promoting high-grade glioma ... Read more >>

Cell Res (Cell research)
[2015, 25(8):891-892]

Cited: 0 times

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