CORM-3 ameliorates neurodegeneration in the amygdala and improves depression- and anxiety-like behavior in a rat model of combined traumatic brain injury and hemorrhagic shock.

Abstract

OBJECTIVE:

Emotional disturbances characterized by depression and anxiety among survivors of traumatic brain injury (TBI) impact the quality of life severely. Currently, there is a lack of effective drug treatment for neurodegeneration induced by TBI, mainly due to failed efficacy of compounds such as corticosteroids, calcium channel blockers, and excitatory amino acid inhibitors. Thus, we sought to continue with our investigation on CORM-3, a water-soluble exogenous carbon monoxide-releasing molecule with excellent anti-inflammatory actions employed in a previous study using a rat model of combined TBI with hemorrhage shock and resuscitation (HSR).

METHODS:

Rats were administrated with CORM-3 after induction of TBI and HSR and examined depressive and anxiety-like behaviors, along with cerebral function employing functional magnetic resonance imaging (MRI) 30-days post-trauma. Also, the following variables were measured: 1) neuronal pyroptosis and apoptosis 24 h post-trauma, 2) the roles of PKG-ERK1/2 signaling pathways with the use of the protein kinase G (PKG) specific inhibitor, KT5823.

RESULTS:

CORM-3-treated rats displayed significant ameliorated depression- and anxiety-like behaviors, improved cerebral blood flow, and fractional anisotropy (FA), showed less neuronal pyroptosis and apoptosis in the amygdala, and upregulated the phosphorylation of Vasodilator-stimulated phosphoprotein (VASP) and ERK1/2. However, CORM-3 neuroprotective effects against trauma were only partially reversed by KT5823.

CONCLUSION:

CORM-3 ameliorated the emotional deficits and neuronal death induced in the amygdala post-TBI and HSR rat model, and PKG-ERK1/2 signaling might be implicated in the underlying mechanism.

• Authors: Yan Li, Li-Min Zhang, Dong-Xue Zhang, Wei-Chao Zheng, Yang Bai, Jing Bai, Lan Fu, Xu-Peng Wang
• Journal: Neurochemistry international (Neurochem Int) Vol. 140 Pg. 104842 (11 2020) ISSN: 1872-9754 [Electronic] England
• PMID: 32858089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Organometallic Compounds
• tricarbonylchloro(glycinato)ruthenium(II)

Topics

• Amygdala (drug effects, metabolism, pathology)
• Animals
• Anxiety (drug therapy, metabolism, pathology)
• Brain Injuries, Traumatic (drug therapy, metabolism, pathology)
• Depression (drug therapy, metabolism, pathology)
• Disease Models, Animal
• Male
• Neurodegenerative Diseases (drug therapy, metabolism, pathology)
• Organometallic Compounds (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (drug therapy, metabolism, pathology)