Traumatic brain injury (TBI) results in the production of peroxynitrite (PN), leading to oxidative damage of lipids and protein. PN-mediated lipid peroxidation (LP) results in production of reactive aldehydes 4-hydroxynonenal (4-HNE) and acrolein. The goal of these studies was to explore the hypothesis that interrupting secondary oxidative damage following a TBI via phenelzine (PZ), analdehyde scavenger, would protect against LP-mediated mitochondrial and neuronal damage. Male Sprague-Dawley rats received a severe (2.2 mm) controlled cortical impact (CCI)-TBI. PZ was administered subcutaneously (s.c.) at 15 min (10 mg/kg) and 12 h (5 mg/kg) post-injury and for the therapeutic window/delay study, PZ was administered at 1 h (10 mg/kg) and 24 h (5 mg/kg). Mitochondrial and cellular protein samples were obtained at 24 and 72 h post-injury (hpi). Administration of PZ significantly improved mitochondrial respiration at 24 and 72 h compared with vehicle-treated animals. These results demonstrate that PZ administration preserves mitochondrial bioenergetics at 24 h and that this protection is maintained out to 72 hpi. Additionally, delaying the administration still elicited significant protective effects. PZ administration also improved mitochondrial Ca 2+ buffering (CB) capacity and mitochondrial membrane potential parameters compared with vehicle-treated animals at 24 h. Although PZ treatment attenuated aldehyde accumulation post-injury, the effects were insignificant. The amount of α-spectrin breakdown in cortical tissue was reduced by PZ administration at 24 h, but not at 72 hpi compared with vehicle-treated animals. In conclusion, these results indicate that acute PZ treatment successfully attenuates LP-mediated oxidative damage eliciting multiple neuroprotective effects following TBI.
|Number of pages||21|
|Journal||Journal of Neurotrauma|
|State||Published - Apr 15 2019|
Bibliographical noteFunding Information:
This work was supported by NIH grants R01 NS083405 and R01 NS084857 from NINDS and by NIH grant P30 NS051220.
© Copyright 2019, Mary Ann Liebert, Inc.
- 4-hydroxynonenal (4-HNE)
- traumatic brain injury (TBI)
ASJC Scopus subject areas
- Clinical Neurology