Arachidonic Acid: A Bridge between Traumatic Brain Injury and Fracture Healing

Abstract

Traumatic brain injury (TBI) is associated with enhanced osteogenesis. The aim of this study was to investigate the effect of serum from TBI rats on fracture healing. Results from this study showed that the serum from TBI rats enhanced the expression of bone gamma carboxyglutamate protein (BGLAP), and promoted in vitro proliferation of MC3T3-E1 cells, a mouse osteoblastic cell line. Furthermore, gas chromatography/mass spectrometry (GC/MS) coupled with multivariate statistical analysis was used to identify the changes in global serum metabolites after TBI. We found that arachidonic acid (AA) was significantly enhanced in serum metabolites in TBI subjects, while hydroxybutyric acid, leucine, malic acid, 5-oxyproline, isocitric acid, mannose, and uric acid were reduced. Finally, we examined the effects of AA on BGLAP expression and cell proliferation in MC3T3-E1 cells. We found that BGLAP expression and proliferation of osteoblasts were positively regulated in the presence of AA. These findings suggest that the increased AA in serum after TBI may play a key role in enhancing the speed of fracture healing.

Improved Fracture Healing in Patients with Concomitant Traumatic Brain Injury: Proven or Not?

“…In the last decade, six clinical studies were published, which found proof of an accelerated callus formation or fracture healing in patient with TBI and concomitant fractures. Five of them were prospective matched-control studies [ 94 , 95 , 98 , 102 , 103 ] with an average patient population of 65.2 (range 28–86) patients and one study was a retrospective, matched-control study [ 101 ], with a patient population of 67 patients.…”

“…The first mainstream is represented in 4 [ 92 , 94 , 95 , 98 ] of the 7 considered articles and puts the human mesenchymal stem cells/skeletal stem cells in focus.…”

“…In the last decade, there were 26 studies on this topic after the publication of Morley and colleagues. About 50% of these studies [ 92 – 98 , 101 – 107 ] find evidence for increased callus formation in cases with concomitant TBI; the other studies are not conclusive.…”

“…They showed that in the presence of arachidonic acid the expression and proliferation of bone gamma carboxyglutamate protein (BGLAP or osteocalcin) is beneficially influenced and thereby the proliferation of the mouse osteoblastic cell line MC3T3-E1 was increased. They suggest a key role for arachidonic acid in the process of enhanced callus formation in rats with a TBI [ 98 ].…”

Roles of elevated 20‑HETE in the breakdown of blood brain barrier and the severity of brain edema in experimental traumatic brain injury

“…Traumatic brain injury (TBI) has been reported to induce the release of arachidonic acid (AA) from cell membranes (1). AA levels have been indicated to be increased by 1,093% within 48 h following TBI and to remain elevated for several days (2). Cytochrome P450 (CYP) enzymes, particularly CYP4A isozymes, catalyze the ω-hydroxylation of AA to 20-hydroxyeicosatetraenoic acid (20-HETE) (3).…”