Cerebrospinal Fluid (CSF) Can Inhibit Wound Healing by Inhibiting Angiogenesis
David Gau, Eric Wang, Ezequiel Goldschmidt, Paul Gardner, Carl Snyderman, Partha Roy, Meghan Schneck, Lauren Carey
Introduction: Pressure on dural edges exerted by cerebrospinal fluid (CSF) is thought to impair proper apposition of the wound borders and therefore prevent healing. It has been observed that tissue exposed to CSF does not bleed and exhibits smooth edges. This raises the question of whether the constituents of CSF themselves impair normal wound healing.
Objective: Here, we investigate whether CSF exhibits anti-angiogenic properties and therefore inhibits the healing process.
Methods: We used an in vitro model, in which human umbilical vein endothelial cells (HuVECS) grow in a three-dimensional scaffold forming capillary-like structures named cords. We exposed the model to CSF and then quantified cord length. Boiled CSF (containing only denaturalized proteins) was used as a secondary control.
Results: In 5 samples, CSF at 50, 75 and 100% significantly diminished cell migration and subsequent formation of capillary-like structures compared to DPBS, which had no effect. Boiled CSF lacked any effect on cord formation. CSF did not affect cell migration of fibroblasts, smooth muscle or endothelial cells.
Conclusions: CSF inhibited cord formation with a dose dependent tendency, implying that it contains signaling molecules that preclude angiogenesis. This effect was cell and process specific. Heat-Denaturalization of the protein contents prevented the anti-angiogenetic effect, signifying that a CSF protein is probably responsible for this phenomenon. These experiments suggest that CSF, rather than acting as an inert bystander, may actively impair healing by inhibiting capillary formation.