D-β-hydroxybutyrate promotes functional recovery and relieves pain hypersensitivity in mice with spinal cord injury.
Spinal cord injury (SCI) leads to severe motor and sensory dysfunction and significantly reduces the quality of life. The aim of the present work was to investigate the effect of administration of exogenous D-β-hydroxybutyrate (DBHB) on functional recovery and neuropathic pain in spinal cord-injured mice.



Mice were given a moderate-severe thoracic spinal contusion injury at the T9-10level and treated with exogenous DBHB.



Treatment of SCI mice with DBHB markedly improved locomotor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. DBHB treatment partly prevented the SCI-induced loss of motor neurons and suppressed microglial and glial activation. DBHB treatment enhanced histone acetylation and up-regulated expression of the transcription factor FOXO3a, catalase and SOD2 in injured region of SCI mice. DBHB treatment suppressed SCI-induced NLRP3 inflammasome activation and reduced protein expression of IL-1β and IL-18. In addition, DBHB treatment improved mitochondrial function and abated oxidative stress following SCI.



DBHB promoted functional recovery and relieved pain hypersensitivity in mice with SCI, possibly through inhibition of histone deacetylation and NLRP3 inflammasome activation and preservation of mitochondrial function. DBHB could thus be envisaged as a potential use of interventions for SCI but remains to be tested in humans.
Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China.
Jiao
J
Qian
Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Wenjun
W
Zhu
Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Ming
M
Lu
Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Bin
B
Ni
Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Jun
J
Yang
D020155:3-Hydroxybutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000188:drug therapy* / Q000473:pathology; D007796:Laminectomy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
D020155:3-Hydroxybutyric Acid