Functional and proteomic analysis of serum and cerebrospinal fluid derived from patients with traumatic brain injury: a pilot study

Abstract

Osteoinductive factors are present in the serum and CSF of brain-injured patients. These may include one or more of those proteins identified as having an affinity for osteoprogenitor cells that are either exclusively present or up- or downregulated in the serum and CSF of brain-injured patients.

Serum After Traumatic Brain Injury Increases Proliferation and Supports Expression of Osteoblast Markers in Muscle Cells

“…Proteomic investigations have demonstrated a change in the profile of serum and cerebrospinal fluid proteins in response to traumatic brain injury that is potentially linked to the osteogenic influence that traumatic brain injury has on fracture-healing 33 . Additionally, serum from subjects with a traumatic injury to the central nervous system has been shown to increase the proliferation and alkaline phosphatase expression of mesenchymal and osteoblastic cells.…”

Understanding heterotopic ossification after spinal cord injury

“…Consistent with this, blood serum from TBI patients has been reported to enhance proliferation and induce expression of osteoblast markers: osterix in cultures of primary skeletal muscle cells [269], and osterix, Runx2 and alkaline phosphatase in the human osteoblastic cell line FOB1.19 [41]. It has been also published earlier that plasma from rodents with severe burns also induced osteogenic differentiation of muscle MPCs [270].…”

“…The ability of plasma from mice with SCI to facilitate mineralization of cultured muscle interstitial cells supports the former hypothesis but does not exclude the latter. Consistent with this, blood serum from TBI patients induces expression of osterix in primary skeletal muscle cells [269], and osterix, Runx2 and alkaline phosphatase in the human osteoblastic cell line FOB1.19 [41]. We have performed gene microarray analysis that revealed up-regulation of inflammatory cytokines IL-1β, TNF-α, IL-6 and CSF-1 together with up-regulation of M2 macrophage markers in SCI-operated mice with CDTXinduced inflammation -the only group that develops NHO.…”

Effect of rat brain tissue extracts on osteoblast proliferation and differentiation

“…The most widely investigated hypothesis is that breakdown of the blood/brain barrier after trauma allows factors that promote osteoblast growth and maturation to be released into the circulation and cause accelerated fracture healing [7,15,[19][20][21][22][23] Mitogenic effect of serum from individuals with traumatic brain injury Experiments to investigate the possibility that mitogenic factors passing through the blood-brain barrier cause increased fracture healing have focused mainly on the mitogenic action of serum on cultured cells. Serum from patients or animals with traumatic brain injury has been shown to have osteogenic activity and a greater mitogenic activity than serum from nonbrain-injured subjects [7,15,19,20,22,23]. Mitogenic activity apparently comes from brain tissue itself, for cerebrospinal fluid (CSF) from traumatic brain injury patients is able to increase osteoblast proliferation [15,21].…”

“…Traumatic brain injury serum contains proteins not found in normal serum that binds to the osteoblast cell surface [20]. A number of possible growth-promoting substances, including bone morphogenetic proteins, have been investigated as possible serum factors responsible for accelerated fracture healing [15,21,[25][26][27], but no definitive results have yet emerged.…”