Authors: Vincent Dodson; Malini Subramaniam, MS; Neil Majmundar, MD; Vanessa Swantic, MS; Aakash Shah, BS; Steven Levison, PhD (Montville, NJ)
Introduction: Traumatic brain injuries (TBI) affect 1.7 million patients each year. Most cases of pediatric TBI are diffuse, closed-head injuries (CHI), resulting in cognitive and behavioral problems. Previously findings from our lab found that mice haplodeficient in leukemia inhibitory factor (LIF) sustain greater damage after CHI. We hypothesize that intranasally administered LIF will reduce brain injury when provided after a CHI. Methods: Juvenile wild-type CD1 mice were administered blunt, closed-head injuries to the parietal lobe. There were three groups (sham, vehicle, and experimental). Experimental and vehicle mice were administered intranasal LIF and water, respectively, starting 4 hours after the injury followed by 6 subsequent intranasal administrations at 12 hour intervals. Sham mice underwent surgery and were sutured without administering a closed-head injury. Behavior outcomes were determined with the modified neurological severity score (mNSS), average time spent traversing an inclined beam, and mean hang time in the four-limb wire test. Western blots and immunofluorescence were performed for Caspase 6 cleaved tubulin, GFAP, Iba-1 and MBP. Results: There was a statistically significant difference in mNSS between groups as determined by the nonparametric Kruskal-Wallis test (H(2)=8.70, p<0.05), with the vehicle group demonstrating the highest scores. There was a trend towards reduced time on the inclined beam for the experimental group. There was no statistically significant difference between groups by average hang time in the four-limb wire test. Axonal damage, as assessed by caspase 6 cleaved tubulin, appeared diminished and there was a trend for reduced white matter astrogliosis in the LIF-treated group, but no change in the microglial response compared to intranasal vehicle treated mice. Conclusion: These data demonstrate that intranasal LIF treatment is viable as a therapeutic, as it has the potential to preserve axonal conductance and abate glial responses as manifested by improved behavioral outcomes after pediatric traumatic brain injury.