Neuroregenerative and protective functions of Leukemia Inhibitory Factor in perinatal hypoxic-ischemic brain injury.

Neuroregenerative and protective functions of Leukemia Inhibitory Factor in perinatal hypoxic-ischemic brain injury. Exp Neurol. 2020 Apr 19;:113324 Authors: Lin J, Niimi Y, Clausi MG, Kanal HD, Levison SW Abstract Neonatal hypoxic-ischemic encephalopathy remains the most important neurological problem of the newborn. Delays in diagnosing perinatal brain injuries are common, preventing access to acute therapies. Therefore, there is a critical need for therapeutic strategies that are beneficial when delivered beyond 24 h after birth. Here we show that Leukemia Inhibitory Factor (LIF) functions as an essential injury-induced neurotrophic cytokine in the CNS and that non-invasively administering LIF as late as 3 days after a hypoxic-ischemic insult improves neurological function. Using a mouse model of late preterm brain injury we show that astroglial and reactivity to hypoxia-ischemia was diminished at 3 days of recovery, but then exacerbated at 2 weeks of recovery in LIF haplodeficient mice. There also were significantly more CD68+/Iba-1+ cells in the ipsilateral striatum in LIF-Het mice compared to WT mice at 2 weeks of recovery. This desynchronized glial response was accompanied by increased neuronal cell death in the striatum and neocortex (Fluorojade C), hypomyelination (reduced MBP staining and thinner external capsule), increased extent of brain damage (Nissl) and diminished neurological function on sensorimotor tests....
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research