Protective effects of phenelzine administration on synaptic and non-synaptic cortical mitochondrial function and lipid peroxidation-mediated oxidative damage following TBI in young adult male rats.

Protective effects of phenelzine administration on synaptic and non-synaptic cortical mitochondrial function and lipid peroxidation-mediated oxidative damage following TBI in young adult male rats. Exp Neurol. 2020 Apr 20;:113322 Authors: Hill RL, Singh IN, Wang JA, Kulbe JR, Hall ED Abstract Traumatic brain injury (TBI) results in mitochondrial dysfunction and induction of lipid peroxidation (LP). Lipid peroxidation-derived neurotoxic aldehydes such as 4-HNE and acrolein bind to mitochondrial proteins, inducing additional oxidative damage and further exacerbating mitochondrial dysfunction and LP. Mitochondria are heterogeneous, consisting of both synaptic and non-synaptic populations, with synaptic mitochondria being more vulnerable to injury-dependent consequences. The goal of these studies was to explore the hypothesis that interrupting secondary oxidative damage following TBI using phenelzine (PZ), an aldehyde scavenger, would preferentially protect synaptic mitochondria against LP-mediated damage in a dose- and time-dependent manner. Male Sprague-Dawley rats received a severe (2.2 mm) controlled cortical impact (CCI)-TBI. PZ (3-30 mg/kg) was administered subcutaneously (subQ) at different times post-injury. We found PZ treatment preserves both synaptic and non-synaptic mitochondrial bioenergetics at 24 h and that this protection is partially maintained out to 72 h post-injury using various dosing regimens. The results fr...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research