Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion. Academic Article uri icon


  • Traumatic brain injury (TBI) precedes the onset of epilepsy in up to 15-20% of symptomatic epilepsies and up to 5% of all epilepsy. Treatment of acquired epilepsies, including post-traumatic epilepsy (PTE), presents clinical challenges, including frequent resistance to anti-epileptic therapies. Considering that over 1.6 million Americans present with a TBI each year, PTE is an urgent clinical problem. Neuroinflammation is thought to play a major causative role in many of the post-traumatic syndromes, including PTE. Increasing evidence suggests that neuroinflammation facilitates and potentially contributes to seizure induction and propagation. The inflammatory cytokine, macrophage migration inhibitory factor (MIF), is elevated after TBI and higher levels of MIF correlate with worse post-traumatic outcomes. MIF was recently demonstrated to directly alter the firing dynamics of CA1 pyramidal neurons in the hippocampus, a structure critically involved in many types of seizures. We hypothesized that antagonizing MIF after TBI would be anti-inflammatory, anti-neuroinflammatory and neuroprotective. The results show that administering the MIF antagonist ISO1 at 30 min after TBI prevented astrocytosis but was not neuroprotective in the peri-lesion cortex. The results also show that ISO1 inhibited the TBI-induced increase in T cells in the gut, and the percent of B cells infiltrating into the brain. The ISO1 treatment also increased this population of B cells in the spleen. These findings are discussed with an eye towards their therapeutic potential for post-traumatic syndromes, including PTE.

published proceedings

  • Int J Mol Sci

author list (cited authors)

  • Newell-Rogers, M. K., Rogers, S. K., Tobin, R. P., Mukherjee, S., & Shapiro, L. A.

citation count

  • 12

complete list of authors

  • Newell-Rogers, M Karen||Rogers, Susannah K||Tobin, Richard P||Mukherjee, Sanjib||Shapiro, Lee A

publication date

  • January 2020