D-?-hydroxybutyrate promotes practical restoration and relieves ache hypersensitivity in mice with spinal twine harm.
Br J Pharmacol. 2017 Jul;174(13):1961-1971
Authors: Qian J, Zhu W, Lu M, Ni B, Yang J
BACKGROUND AND PURPOSE: Spinal twine harm (SCI) results in extreme motor and sensory dysfunction and considerably reduces the standard of life. The goal of the current work was to analyze the impact of administration of exogenous D-?-hydroxybutyrate (DBHB) on practical restoration and neuropathic ache in spinal cord-injured mice.
EXPERIMENTAL APPROACH: Mice got a moderate-severe thoracic spinal contusion harm on the T9-10 stage and handled with exogenous DBHB.
KEY RESULTS: Therapy of SCI mice with DBHB markedly improved locomotor perform and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. DBHB remedy partly prevented the SCI-induced lack of motor neurons and suppressed microglial and glial activation. DBHB remedy enhanced histone acetylation and up-regulated expression of the transcription issue FOXO3a, catalase and SOD2 in injured area of SCI mice. DBHB remedy suppressed SCI-induced NLRP3 inflammasome activation and lowered protein expression of IL-1? and IL-18. As well as, DBHB remedy improved mitochondrial perform and abated oxidative stress following SCI.
CONCLUSIONS AND IMPLICATIONS: DBHB promoted practical restoration and relieved ache hypersensitivity in mice with SCI, probably via inhibition of histone deacetylation and NLRP3 inflammasome activation and preservation of mitochondrial perform. DBHB may thus be envisaged as a possible use of interventions for SCI however stays to be examined in people.
PMID: 28320049 [PubMed – indexed for MEDLINE]