Excitotoxic neuronal death, associated with neurodegenerative disorders and hypoxic insults, results from excessive exposure to excitatory neurotransmitters. Glutamate neurotoxicity is triggered primarily by massive Ca2+ influx arising from overstimulation of the NMDA subtype of glutamate receptors. The underlying mechanisms, however, remain elusive. We have tested the hypothesis that mitochond...

PURPOSE To elucidate the role of the glial glutamate transporter GLAST, in the regulation of retinal function. METHODS Antisense oligonucleotides to GLAST were injected intravitreally into the left eye of Wistar rats. Sense oligonucleotides (control) were injected into the right eye over a period of 3 days. Scotopic flash electroretinograms were recorded over a 20-day period. To assay whether...

BACKGROUND AND PURPOSE Excitotoxicity is a component of many neurodegenerative diseases. The signaling events that lead from excitotoxic injury to neuronal death remain incompletely defined. Pharmacological approaches have shown that nitric oxide production is critical for the progression of neurodegeneration after the initiation of excitotoxicity by the glutamate analog kainate. Although nitri...

Schizas, N. 2015. Neuroprotection in the Injured Spinal Cord. Novel Strategies using Immunomodulation, Stem cell Transplantation and Hyaluronic acid Hydrogel carriers. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1106. 59 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9255-7. The overall aim of this thesis was to establish strategies to min...

BACKGROUND The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used Organotypic Entorhino-Hippocampal Slice Cultures (OHSC) and investigated the temporal regulation of...

It has been claimed over the years—most recently in this journal and several others—that neuronal degeneration in adult brain arising during chronic alcohol exposure is, or is likely to be, via " excitotoxicity " A purpose of this opinion piece is to reinforce a view, noted earlier (Collins and Neafsey, 2012), that an excitotoxic mechanism underlying alcoholic neurodamage in the mature brain ha...

Protease nexin-I (PN-1) is a 44 kDa serine proteinase inhibitor that rapidly inhibits thrombin by forming SDS stable complexes with serine at the catalytic site of the protease. Levels of both PN-1 and thrombin are increased in the brain in response to insults such as ischemia, suggesting roles in neural injury and repair processes. We now report that PN-1-protected cultured rat hippocampal neu...

Neuronal cell death can be determined by the overall level of reactive oxygen species (ROS) resulting from the combination of extrinsic sources and intrinsic production as a byproduct of oxidative phosphorylation. Key controllers of the intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By allowing a controlled leak of protons across the inner mitochondrial membrane a...

We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (approximately 120) under the control of the endogenous human promoter (shortstop). Frequent and widespread htt inclusions occur early in shortstop mice. Despite these inclusions, shortstop mice display no clinical evidence of neuronal dysfunction and no...