PACAP38 suppresses cortical damage in mice with traumatic brain injury by enhancing antioxidant activity.

Abstract

The production of reactive oxygen species (ROS) and the resulting oxidative stress in mice in response to a controlled cortical impact (CCI) are typical exacerbating factors associated with traumatic brain injury (TBI). Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a multifunctional peptide that has been shown to exhibit neuroprotective effects in response to a diverse range of injuries to neuronal cells. We recently reported that PACAP38 might regulate oxidative stress in mice. The aim of the present study was to determine whether PACAP38 exerts neuroprotective effects by regulating oxidative stress in mice with TBI. Reactive oxidative metabolites (ROMs) and biological antioxidant potential (BAP) were measured in male C57Bl/6 mice before and 3, 4, and 24 h after CCI. PACAP38 was administered intravenously immediately following CCI, and immunostaining for the oxidative stress indicator nitrotyrosine (NT), and for neuronal death as an indicator of the area affected by TBI, was measured 24 h later. Western blot experiments to determine antioxidant activity [as indicated by superoxide dismutase-2 (SOD-2) and glutathione peroxidase 1 (GPx-1)] in the neocortical region were also performed 3 h post-CCI. Results showed that plasma BAP and ROM levels were dramatically increased 3 h after CCI. PACAP38 suppressed the extent of TBI and NT-positive regions 24 h after CCI, and increased SOD-2 and GPx-1 levels in both hemispheres. Taken together, these results suggest that increasing antioxidant might be involving in the neuroprotective effect of PACAP38 in mice subjected to a CCI.

• Authors: Kazuyuki Miyamoto, Tomomi Tsumuraya, Hirokazu Ohtaki, Kenji Dohi, Kazue Satoh, Zhifang Xu, Sachiko Tanaka, Norimitsu Murai, Jun Watanabe, Koichi Sugiyama, Tohru Aruga, Seiji Shioda
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 54 Issue 3 Pg. 370-9 (Nov 2014) ISSN: 1559-1166 [Electronic] United States
• PMID: 24907941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pituitary Adenylate Cyclase-Activating Polypeptide
• Reactive Oxygen Species
• Glutathione Peroxidase
• Superoxide Dismutase
• superoxide dismutase 2
• Glutathione Peroxidase GPX1
• Gpx1 protein, mouse

Topics

• Animals
• Brain Injuries (drug therapy, metabolism)
• Glutathione Peroxidase (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Neocortex (drug effects, metabolism)
• Oxidative Stress
• Pituitary Adenylate Cyclase-Activating Polypeptide (pharmacology, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)
• Glutathione Peroxidase GPX1