Inflammation near the nerve cell body enhances axonal regeneration

Abstract

Although crushed axons in a dorsal spinal root normally regenerate more slowly than peripheral axons, their regeneration can be accelerated by a conditioning lesion to the corresponding peripheral nerve. These and other observations indicate that injury to peripheral sensory axons triggers changes in their nerve cell bodies that contribute to axonal regeneration. To investigate mechanisms of activating nerve cell bodies, an inflammatory reaction was provoked in rat dorsal root ganglia (DRG) through injection of Corynebacterium parvum. This inflammation enhanced regeneration in the associated dorsal root, increasing 4-fold the number of regenerating fibers 17 d after crushing; peripheral nerve regeneration was not accelerated. A milder stimulation of dorsal root regeneration was detected after direct injection of isogenous macrophages into the ganglion. It is concluded that changes favorable to axonal regeneration can be induced by products of inflammatory cells acting in the vicinity of the nerve cell body. Satellite glial cells and other unidentified cells in lumbar DRG were shown by thymidine radioautography to proliferate after sciatic nerve transection or injection of C. parvum into the ganglia. Intrathecal infusion of mitomycin C suppressed axotomy-induced mitosis of satellite glial cells but did not impede axonal regeneration in the dorsal root or the peripheral nerve. Nevertheless, the similarity in reactions of satellite glial cells during 2 processes that activate neurons adds indirect support to the idea that non-neuronal cells in the DRG might influence regenerative responses of primary sensory neurons.

Oncomodulin links inflammation to optic nerve regeneration

“…The innate immune response in the central nervous system (CNS) is mediated by resident microglia, astrocytes, and infiltrating macrophages and neutrophils that can release numerous anti-and pro-inflammatory cytokines, chemokines, growth factors, and other signals. Although some of these factors are toxic to neurons, inflammation has been shown to promote axon regeneration and/or enhance cell survival in the optic nerve (5-9), dorsal roots (10,11), and spinal cord (12,13,14) after injury. In the optic nerve, a CNS pathway that normally shows little capacity to regenerate when injured, peripheral nerve implants into the eye, lens injury, or intraocular injections of zymosan all cause macrophages to enter the eye and stimulate retinal ganglion cells (RGCs) to regenerate lengthy axons beyond the injury site (7,8,15).…”

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

“…Modification of the CNS milieu enhances the sprouting or regeneration of several classes of axons (5,9,10). Neuronintrinsic mechanisms are also vital in recruiting axonal regeneration, illustrated by studies showing that ''conditioning'' of the peripheral process of a sensory axon enhances growth after transection of its central axon (11)(12)(13).…”

“…However, corticospinal axons do not regenerate into a permissive matrix placed in a lesion site, even when that matrix contains NT-3 and lacks inhibitory extracellular matrix molecules or myelin-associated inhibitors (14,15). Further, conditioning of the motor cortex by growth factor infusion (16) or ischemic preconditioning (17) fails to elicit corticospinal axonal regeneration, in contrast to effects of conditioning lesions on sensory axon regeneration (11)(12)(13). Thus, the growth capacity of postdevelopmental, adult corticospinal neurons appears to be severely limited.…”

Herpes simplex virus infection of murine sensory ganglia induces proliferation of neuronal satellite cells

“…In infected ganglia, these cells morphologically resemble infiltrating immune cells. Differing approaches have been taken to the controversial issue of identifying SCs, including morphology and perineural position (Cecchini et al, 1999;Lu & Richardson, 1991;Shimeld et al, 1995), staining for SC marker GFAP and lack of staining for macrophage marker ED2 (Zhou et al, 1999), and S100 staining (Bradley et al, 1997). Confirmation of SC identity is hampered by the reported lack of expression of the SC-specific markers GFAP and S100 during SC proliferation (Wen et al, 1994).…”