Anti-CD14 Monoclonal Antibody in a Mouse Model of Severe Traumatic Brain Injury: Effects on Acute Neuroinflammation...

Traumatic brain injury (TBI) is a debilitating disease that affects millions of people globally every year. Neuroinflammation following TBI is a key driver of neurodegeneration. The microglia, resident innate immune cells in the brain, are major contributors to neuroinflammation following TBI. Toll-like receptors (TLRs) are involved in initiating the microglial response to danger signaling molecules released after TBI. To initiate downstream signaling, TLRs require a coreceptor such as cluster of differentiation 14 (CD14), which is a coreceptor for numerous TLRs. Consequently, CD14 is a good bottleneck target to modulate neuroinflammation after TBI. Because damage to the blood-brain barrier in TBI allows antibodies to enter the injured brain, we explored the effects of an anti-CD14 monoclonal antibody (anti-CD14 mAb) as a potential treatment for TBI. Effects of anti-CD14 mAb, administered at 3 h or 6 h after injury, on neurological status, motor function, inflammation, and brain damage were examined in a mouse controlled cortical impact injury model. Treatment with the mAb had a beneficial effect on acute sensorimotor function. It reduced expression of the markers of acute inflammation IL-1β and CD68, and of a marker of oxidative stress, MnSOD, and was associated with an increase in anti-inflammatory CD206-positive cells in the brain. Administration of anti-CD14 mAb also had a neuroprotective function. For several end-points, the effect of treatment at 6 h was greater than for treatment at 3 h. These findings support the performance of studies to explore long term outcomes of anti-CD14 mAb administered 6 h after injury as a treatment for TBI.