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- Title
Acid Sphingomyelinase Inhibitor, Imipramine, Reduces Hippocampal Neuronal Death after Traumatic Brain Injury.
- Authors
Lee, Si Hyun; Kho, A Ra; Lee, Song Hee; Hong, Dae Ki; Kang, Beom Seok; Park, Min Kyu; Lee, Chang Juhn; Yang, Hyun Wook; Woo, Seo Young; Park, Se Wan; Kim, Dong Yeon; Choi, Bo Young; Suh, Sang Won
- Abstract
Traumatic brain injury (TBI) broadly degrades the normal function of the brain after a bump, blow, or jolt to the head. TBI leads to the aggravation of pre-existing brain dysfunction and promotes neurotoxic cascades that involve processes such as oxidative stress, loss of dendritic arborization, and zinc accumulation. Acid sphingomyelinase (ASMase) is an enzyme that hydrolyzes sphingomyelin to ceramide in cells. Under normal conditions, ceramide plays an important role in various physiological functions, such as differentiation and apoptosis. However, under pathological conditions, excessive ceramide production is toxic and activates the neuronal-death pathway. Therefore, we hypothesized that the inhibition of ASMase activity by imipramine would reduce ceramide formation and thus prevent TBI-induced neuronal death. To test our hypothesis, an ASMase inhibitor, imipramine (10 mg/kg, i.p.), was administrated to rats immediately after TBI. Based on the results of this study, we confirmed that imipramine significantly reduced ceramide formation, dendritic loss, oxidative stress, and neuronal death in the TBI-imipramine group compared with the TBI-vehicle group. Additionally, we validated that imipramine prevented TBI-induced cognitive dysfunction and the modified neurological severity score. Consequently, we suggest that ASMase inhibition may be a promising therapeutic strategy to reduce hippocampal neuronal death after TBI.
- Subjects
BRAIN injuries; SPHINGOMYELINASE; IMIPRAMINE; HIPPOCAMPUS (Brain); CERAMIDES
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 23, p14749
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms232314749