Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Neuroprotective Effects of the Glutamate Transporter Activator (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) following Traumatic Brain Injury in the Adult Rat
Journal of neurotrauma, v 33(11), pp 1073-1083
01 Jun 2016
PMID: 26200170
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Traumatic brain injury (TBI) in humans and in animals leads to an acute and sustained increase in tissue glutamate concentrations within the brain, triggering glutamate-mediated excitotoxicity. Excitatory amino acid transporters (EAATs) are responsible for maintaining extracellular central nervous system glutamate concentrations below neurotoxic levels. Our results demonstrate that as early as 5min and up to 2h following brain trauma in brain-injured rats, the activity (V-max) of EAAT2 in the cortex and the hippocampus was significantly decreased, compared with sham-injured animals. The affinity for glutamate (K-M) and the expression of glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST) were not altered by the injury. Administration of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a GLT-1 activator, beginning immediately after injury and continuing for 24h, significantly decreased neurodegeneration, loss of microtubule-associated protein 2 and NeuN (+) immunoreactivities, and attenuated calpain activation in both the cortex and the hippocampus at 24h after the injury; the reduction in neurodegeneration remained evident up to 14 days post-injury. In synaptosomal uptake assays, MS-153 up-regulated GLT-1 activity in the naive rat brain but did not reverse the reduced activity of GLT-1 in traumatically-injured brains. This study demonstrates that administration of MS-153 in the acute post-traumatic period provides acute and long-term neuroprotection for TBI and suggests that the neuroprotective effects of MS-153 are related to mechanisms other than GLT-1 activation, such as the inhibition of voltage-gated calcium channels.
Metrics
Details
- Title
- Neuroprotective Effects of the Glutamate Transporter Activator (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153) following Traumatic Brain Injury in the Adult Rat
- Creators
- Andreia Cristina Karklin Fontana - Drexel UniversityDouglas P. Fox - Drexel UniversityArgie Zoubroulis - Drexel UniversityOle Valente Mortensen - Drexel UniversityRamesh Raghupathi - Drexel University
- Publication Details
- Journal of neurotrauma, v 33(11), pp 1073-1083
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 11
- Grant note
- 001564-002 / DUCOM R01NS065017 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 5R01NS065017-03 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pharmacology and Physiology
- Web of Science ID
- WOS:000376984600011
- Scopus ID
- 2-s2.0-84971372896
- Other Identifier
- 991019167826604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences