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Increasing functional recovery after a cervical spinal cord injury Plunet, Ward Thomas

Abstract

Spinal cord injury (SCI) in adult mammals results in a loss of function with minimal spontaneous recovery due to secondary damage, the inhibitory nature of the injured adult CNS, and the weak intrinsic axonal growth response of injured neurons. In an attempt to increase the weak growth response I tested if pretreatment of rubrospinal neurons with brain-derived neurotrophic factor (BDNF) one week prior to axotomy or at time of injury would produce functional improvements. Both treatments reduced cell body atrophy and dieback of rubrospinal axons, indicating a cell body response was elicited. However, neither BDNF pretreatment nor acute treatment promoted rubrospinal tract regeneration. In addition, the two-fold increase in rubrospinal tract sprouting into the gray matter rostral to the lesion site did not reach significance. Despite the lack of rubrospinal regeneration, BDNF pretreatment improved functional recovery while BDNF-acute treatment had no effect. The BDNF-treated animals had reduced weight gain and BDNF infusion into the brain has been shown to inhibit food intake. Reduced food intake (dietary restriction) is known to extend lifespan since the 1930s but was recently found to be neuroprotective. I explored the possibility that the improved recovery in the BDNF pretreatment animals was mediated via dietary restriction by testing whether every-other-day fasting (EODF) started one month prior to SCI and continued in the post-injury testing period would also prove effective. EODF animals displayed improved functional recovery, reduced GFAP immunostaining, smaller lesion sizes, and greater numbers of healthy neurons surrounding the lesion area. To test a more clinically relevant treatment I next examined if EODF would promote recovery if initiated after a SCI. EODF promoted better recovery on three independent behavioral tests [i.e. behavioural tests]. Lesion size was dramatically reduced and there was an increase of surviving neurons in the EODF animals. Additionally, there was an increase of corticospinal tract sprouting proximal and distal to the lesion site. The expression of trkB (receptor for BDNF) was changed both at, and distal to, the lesion site, which could play a role in both the neuroprotection and increased plasticity observed.

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