Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons

Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site.Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.Evidence from studies on dorsal root ganglion (DRG) neurons and retinal ganglion cells (RGCs) suggests that the induction of an inflammatory response around the cell bodies of axotomised neurons enhances the regeneration of their axons. Injection of corynebacterium into DRG prior to dorsal root injury produces a fourfold increase in the number of regenerating axons [1]. Similarly, injection of zymosan into the vitreous body of the eye induces extensive but transient regeneration of RGC axons in the crushed optic nerve [2]. Lens injury has similar effects on RGC axonal regeneration, probably because it stimulates the accumulation of macrophages in the retina [2]. Furthermore, adult RGCs grown in media conditioned by activated macrophages also display enhanced neurite growth [3].Against this background we have investigated the possibility that LPS-induced inflammation around the cell bodies of corticospinal tract neurons would enhance their expression of growth-associated genes (c-jun, ATF3, SCG10 and GAP-43) and promote regeneration of their axons following spinal cord injury. It is of particular importance and interest to investigate these questions in relation to corticospinal neurons because their axons constitute the major descending motor pathway, and bec