Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration. As observed following acute excitotoxic insult, complete functional recovery was evident within 7 days of discontinuing the AMPA infusion. Distortion product otoacoustic emissions were not affected by chronic AMPA infusion, suggesting that trauma to outer hair cells did not contribute to AMPA-induced deficits in acoustic sensitivity. Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1121/1.1772395 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABA receptors under ischemic conditions by inhibiting fast receptor recycling.
Sci Rep
January 2025
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
GABA receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABA receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors.
View Article and Find Full Text PDFNeurosteroid replacement therapy using tiagabine and zuranolone restores cerebellar neurodevelopment and reduces hyperactive behaviour following preterm birth.
J Dev Orig Health Dis
January 2025
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults.
View Article and Find Full Text PDFCerebrolysin Induces Motor Recovery Along with Plastic Changes in Motoneurons and an Increase in GAP43 Protein in the Ventral Spinal Cord Following a Kainic Acid Excitotoxic Lesion in the Rat Motor Cortex.
Neurochem Res
November 2024
División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
Lesions in the motor cortex induced by contusions or pathological insults can exert the degeneration of afferent neurons lying distal to these lesions. Axon degeneration and demyelination are hallmarks of several diseases sharing pathophysiological and clinical characteristics. These conditions are very disabling due to the disruption of motor abilities, with lesions that affect this area proving to be a therapeutic challenge, which has driven increasing efforts to search for treatments.
View Article and Find Full Text PDFImpairment of neuronal tyrosine phosphatase STEP worsens post-ischemic inflammation and brain injury under hypertensive condition.
J Neuroinflammation
October 2024
Department of Neurology, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, NM, 87131, USA.
Hypertension is associated with poor outcome and higher mortality in patients with ischemic stroke. The impairment of adaptive vascular mechanisms under hypertensive condition compromises collateral blood flow after arterial occlusion in patients with acute ischemic stroke resulting in hypoperfusion. The increased oxidative stress caused by hypoperfusion is thought to be a trigger for the rapid evolution of ischemic infarct volume under hypertensive condition.
View Article and Find Full Text PDFEffect of Electromagnetic Field on Proliferation and Migration of Fibroblasts and Keratinocytes: Implications in Wound Healing and Regeneration.
J Biotechnol Biomed
September 2024
Department of Translational Research, Western University of Health Sciences, Pomona, California 91766, USA.
Proliferation and migration of fibroblasts, keratinocytes, and endothelial cells are key events in the physiological process of wound healing. This process includes different but overlapping stages: hemostasis, inflammatory phase, the proliferative phase, and the remodeling phase. Traumatic brain injury (TBI) is defined as a mechanical insult to the brain from external mechanical force (primary injury), usually followed by the secondary injury including edema, inflammation, excitotoxicity, oxidative stress, or mitochondrial dysfunction.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!