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Bone Anabolic Response in the Calvaria Following Mild Traumatic Brain Injury is Mediated by the Cannabinoid-1 Receptor.
- Source :
-
Scientific reports [Sci Rep] 2019 Nov 07; Vol. 9 (1), pp. 16196. Date of Electronic Publication: 2019 Nov 07. - Publication Year :
- 2019
-
Abstract
- Brain trauma was clinically associated with increased osteogenesis in the appendicular skeleton. We showed previously in C57BL/6J mice that mild traumatic brain injury (mTBI) transiently induced bone formation in the femur via the cannabinoid-1 (CB1) receptor. Here, we subjected ICR mice to mTBI and examined the bone response in the skull using microCT. We also measured mast cell degranulation (MCD)72 h post-injury. Finally, we measured brain and calvarial endocannabinoids levels post-mTBI. mTBI led to decreased bone porosity on the contralateral (untouched) side. This effect was apparent both in young and mature mice. Administration of rimonabant (CB1 inverse agonist) completely abrogated the effect of mTBI on calvarial porosity and significantly reduced MCD, compared with vehicle-treated controls. We also found that mTBI resulted in elevated levels of anandamide, but not 2-arachidonoylglycerol, in the contralateral calvarial bone, whereas brain levels remained unchanged. In C57BL/6J CB1 knockout mice, mTBI did not reduce porosity but in general the porosity was significantly lower than in WT controls. Our findings suggest that mTBI induces a strain-specific CB1-dependent bone anabolic response in the skull, probably mediated by anandamide, but seemingly unrelated to inflammation. The endocannabinoid system is therefore a plausible target in management of bone response following head trauma.
- Subjects :
- Animals
Arachidonic Acids metabolism
Brain Injuries, Traumatic pathology
Endocannabinoids metabolism
Glycerides metabolism
Male
Mast Cells
Mice
Mice, Inbred ICR
Mice, Knockout
Polyunsaturated Alkamides metabolism
Rimonabant pharmacology
Skull pathology
Brain Injuries, Traumatic metabolism
Receptor, Cannabinoid, CB1 metabolism
Skull metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 31700010
- Full Text :
- https://doi.org/10.1038/s41598-019-51720-w