Physiology and Pharmacology Publications
CRF Mediates Stress-Induced Pathophysiological High-Frequency Oscillations in Traumatic Brain Injury
Document Type
Article
Publication Date
3-1-2019
Journal
eNeuro
Volume
6
Issue
2
URL with Digital Object Identifier
10.1523/ENEURO.0334-18.2019
Abstract
Copyright © 2019 Narla et al. It is not known why there is increased risk to have seizures with increased anxiety and stress after traumatic brain injury (TBI). Stressors cause the release of corticotropin-releasing factor (CRF) both from the hypothalamic pituitary adrenal (HPA) axis and from CNS neurons located in the central amygdala and GABAergic interneurons. We have previously shown that CRF signaling is plastic, becoming excitatory instead of inhibitory after the kindling model of epilepsy. Here, using Sprague Dawley rats we have found that CRF signaling increased excitability after TBI. Following TBI, CRF type 1 receptor (CRFR1)-mediated activity caused abnormally large electrical responses in the amygdala, including fast ripples, which are considered to be epileptogenic. After TBI, we also found the ripple (120-250 Hz) and fast ripple activity (>250 Hz) was cross-frequency coupled with θ (3-8 Hz) oscillations. CRFR1 antagonists reduced the incidence of phase coupling between ripples and fast ripples. Our observations indicate that pathophysiological signaling of the CRFR1 increases the incidence of epileptiform activity after TBI. The use for CRFR1 antagonist may be useful to reduce the severity and frequency of TBI associated epileptic seizures.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Notes
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
The article is available at:
CRF Mediates Stress-Induced Pathophysiological High-Frequency Oscillations in Traumatic Brain Injury. Chakravarthi Narla, Paul S. Jung, Francisco Bautista Cruz, Michelle Everest, Julio Martinez-Trujillo, Michael O. Poulter. eNeuro 30 April 2019, 6 (2) ENEURO.0334-18.2019; DOI: 10.1523/ENEURO.0334-18.2019