Dietary restriction started after spinal cord injury improves functional recovery.
Spinal cord injury typically results in limited functional recovery. Here we investigated whether therapeutic dietary restriction, a multi-faceted, safe, and clinically-feasible treatment, can improve outcome from cervical spinal cord injury. The well-established notion that dietary restriction increases longevity has kindled interest in its potential benefits in injury and disease. When followed for several months prior to insult, prophylactic dietary restriction triggers multiple molecular responses and improves outcome in animal models of stroke and myocardial infarction. However, the efficacy of the clinically-relevant treatment of post-injury dietary restriction is unknown. Here we report that "every-other-day fasting" (EODF), a form of dietary restriction, implemented after rat cervical spinal cord injury was neuroprotective, promoted plasticity, and improved behavioral recovery. Without causing weight loss, EODF improved gait-pattern, forelimb function during ladder-crossing, and vertical exploration. In agreement, EODF preserved neuronal integrity, dramatically reduced lesion volume by >50%, and increased sprouting of corticospinal axons. As expected, blood beta-hydroxybutyrate levels, a ketone known to be neuroprotective, were increased by 2-3 fold on the fasting days. In addition, we found increased ratios of full-length to truncated trkB (receptor for brain-derived neurotrophic factor) in the spinal cord by 2-6 folds at both 5 days (lesion site) and 3 weeks after injury (caudal to lesion site) which may further enhance neuroprotection and plasticity. Because EODF is a safe, non-invasive, and low-cost treatment, it could be readily translated into the clinical setting of spinal cord injury and possibly other insults.
Plunet
Ward T
WT
International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
Streijger
Femke
F
Lam
Clarrie K
CK
Lee
Jae H T
JH
Liu
Jie
J
Tetzlaff
Wolfram
W
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D031204:Caloric Restriction / Q000379:methods*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005508:Food Deprivation; D005526:Food, Formulated; D020439:Growth Cones / Q000378:metabolism; D007794:Lameness, Animal / Q000178:diet therapy / Q000209:etiology / Q000503:physiopathology; D008297:Male; D009416:Nerve Regeneration; D009473:Neuronal Plasticity; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D020127:Recovery of Function; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D020155:3-Hydroxybutyric Acid