Printed Poster | Session 1

008 – Interleukin-4 promotes corticospinal regeneration in mouse and man

Nicholas Hanuscheck (1) – Frauke Zipp (1) – Christina F. Vogelaar (1)
Department of Neurology, University Medical Center, Johannes Gutenberg University, Mainz, Germany (1)

Traumatic spinal cord injury (SCI) is a sudden and devastating condition that remains uncured. Unlike neurons of the peripheral nervous system, central nervous system (CNS) neurons that project long axons into the spinal cord exhibit a poor regenerative capacity. Despite being indispensable for voluntary motor functions, axons of the corticospinal tract (CST) display the least regeneration among all tracts leaving patients with yet untreatable severe disability. Based on our recent findings of fast direct neuronal Interleukin-4 (IL-4) signalling inducing neuroprotection (Vogelaar et al, Sci Transl Med. 2018), we hypothesized IL-4 as a putative target for inducing CST regeneration.
Here, we use motor cortex layer V (CxV) explant cultures to grow CST axons in vitro and developed an assay to assess the regeneration-promoting efficacy of IL-4 in CST damage. Following axonal transsection, we observed enhanced growth cone formation and neurite outgrowth of IL-4 treated CxV explant cultures. Strikingly, IL-4 also enhanced neurite outgrowth in human CST neurons, corroborating its regenerative effects in CNS damage. Summarized, we conclude that IL-4 triggers neuron-intrinsic regeneration mechanisms in both human and mouse CST neurons and therefore, represents a putative growth-promoting treatment for traumatic CNS injury.