Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation.

Traumatic brain injury (TBI) frequently leads to cognitive impairments. The toll-like receptor 4 (TLR4) ligand, Monophosphoryl lipid A (MPL), has shown promise in modulating neuroinflammatory responses after TBI. We investigated the effects of MPL on spatial memory, passive avoidance memory, neuronal survival, and inflammatory/anti-inflammatory cytokines in rat brain following mild-to-moderate TBI. Rats underwent a learning period in the Morris water maze and shuttle box, followed by TBI induction by controlled cortical impact. MPL was administered into the cerebral ventricle 20 min after TBI. Spatial memory was assessed 7 and 28 days later. Passive avoidance memory was assessed 2 and 6 days after TBI. MPL significantly improved the spatial memory deficit at 7 days but not 28 days after TBI. It also improved impairment of the avoidance memory at both 2 and 6 days after TBI. MPL prohibited the TBI-induced TNF-α increase and IL-10 decrease in the injured region at 7 days post-TBI period. MPL prevented the neuronal loss induced by TBI in the hippocampus. A single administration of MPL shortly after TBI alleviates short-term memory deficits, through anti-inflammatory and anti-cell loss activities. Repeated MPL administration may also inhibit the long-term memory deficits after TBI.