Neurotrophins Reduce Degeneration of Injured Ascending Sensory and Corticospinal Motor Axons in Adult Rat Spinal Cord

Abstract

Spinal cord regeneration in adult mammals is limited by neurite outgrowth inhibitors and insufficient availability of outgrowth-promoting agents. Formation of degenerative swellings at the proximal ends of severed axons (terminal clubs), which starts early after injury, also may hinder recovery and their rupture may contribute to secondary spinal cord damage. We investigated whether neurotrophins would reduce these degenerative processes. Adult rats received a transection of the dorsal column sensory and corticospinal motor tracts at T9 and anterograde tracing of the axons from the sciatic nerve and motor cortex, respectively. The highest number of terminal clubs was found at 1 day and approximately half remained present until at least 28 days. A single injection immediately after injury of a mixture of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 into the lesion site, reduced the number of terminal clubs in the sensory system by approximately half at 1 and 7 days (but not 14) after the lesion. Individual or combinations of two neurotrophins were as effective, suggesting that the neurotrophins protected similar axonal populations. The injected neurotrophins did not affect degeneration of corticospinal motor axons. A 7-day continuous intrathecal infusion of neurotrophin-3 was more effective and also reduced terminal club formation of corticospinal axons by ∼60%. Spinal tissue loss was not affected by the neurotrophin treatments, suggesting that terminal clubs are not major contributors to the pathogenesis of secondary spinal degeneration during the first two weeks. Thus, neurotrophins can reduce axonal degeneration in the spinal cord after traumatic axonal injury.