Optic neuritis (ON) is an inflammatory, demyelinating, neurodegenerative, and presently untreatable condition of the optic nerve which might induce blindness. Environmental enrichment (EE) consists of a manipulation in which animals are exposed to complex conditions through adaptations in the physical and social environment. This complex environment is composed by nesting materials, running wheels for voluntary exercise, tunnels, ladders, and toys with different textures, colors, shapes, and sizes, which are moved around daily to stimulate novelty, and provide continuous opportunity for exploration and stimulating sensory, cognitive, and physical activity. We analyzed the effect of environmental enrichment (EE) on visual pathway damage provoked by experimental ON induced by a microinjection of bacterial lipopolysaccharide (LPS) into the optic nerve. For this purpose, LPS was
microinjected into the optic nerve from male Wistar rats. After injection, one group of animals was submitted to EE, and another group remained in standard environment (SE) for 21 days. EE prevented the decrease in pupil light reflex (PLR), visual evoked potentials, retinal anterograde transport, phosphorylated neurofilament immunoreactivity, myelination (luxol fast blue staining), and axon (toluidine blue staining) and retinal ganglion cell (Brn3a-immunoreactivity) number. EE also prevented microglial/macrophage reactivity (Iba-1- and ED1-immunoreactivity), and astrocytosis (glial fibrillary acidic protein-immunostaining) induced by experimental ON. LPS-injected optic nerves displayed oxidative damage and increased inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β and TNFα mRNA levels which were prevented by EE. EE increased optic nerve brain-derived neurotrophic factor levels. When EE started at 4 (but not 7) days post-injection of LPS, a preservation of the PLR was observed at 21 days post-LPS, which was blocked by the daily administration of ANA-12 (a TrkB receptor antagonist) from day 4 to day 7 post-LPS. Moreover, EE from day 4 to day 7 post-LPS significantly preserved the PLR at 21 days post-injection. The present results show that EE protected the visual
pathway function and structure against experimental ON. Although care must be taken when extrapolating data obtained in experimental models to humans, the protective effect of EE could reflect a scenario in which a physically and mentally active lifestyle promotes the visual pathway resiliency to disruption induced by neuroinflammation.