Impact of Dietary Folate on Respiratory Recovery after Cervical SCI
Authors: Ciesla Marissa C. , Seven Yasin B. , Allen Latoya L. , Smith Kristin N. , Asa Zachary A. , Iskandar Bermans J. , Gonzalez‐Rothi Elisa J. , Mitchell Gordon S. 
Published: June 2021

While much is known regarding folate's role in neural development, little is known concerning its effects in the adult central nervous system (CNS), particularly following injury or trauma. There is some evidence that folate enhances spinal sensory axon regrowth into a peripheral nerve graft after dorsal column injury. Further, 6 weeks after thoracic spinal contusion, folate supplementation elicits small but significant improvements in locomotor function in rats. Although surveys of individuals with chronic spinal cord injury (SCI) report reduced dietary folate intake, the impact folate intake on functional recovery after SCI is not known. Since respiratory dysfunction is the leading cause of death after cervical SCI, we investigated the effects of folate supplementation and deprivation on respiratory motor function after spinal hemisection at C2 (C2Hx). We hypothesized that folate supplementation would improve, while folate deprivation would hinder breathing recovery after C2Hx. In adult male Sprague Dawley rats with C2Hx, we compared the effects of a: 1) normal diet (4mg/kg folate in chow), 2) normal diet with supplemental folate injections (80ug/kg/day), and 3) folate deprivation (0 mg/kg folate in chow). Animals received their respective diets beginning 1 month prior to injury, and continued through the study duration. Intraperitoneal folate injections in the supplemented group were initiated 3 days prior to C2Hx and continued daily for 2 weeks post‐injury. Bilateral diaphragm electromyography (EMG) recordings were made in urethane anesthetized spontaneously breathing rats at 2 and 8 weeks post‐injury during normoxia (arterial PO2 ~90mmHg, PCO2 ~45mmHg), maximal chemoreceptor stimulation (10.5% O2/7% CO2), spontaneous augmented breaths (sighs), and sustained airway occlusion (40 sec). We did not see any consistent folate effects on ipsilateral or contralateral diaphragm EMG function at either 2 or 8 weeks post injury (P>0.05 for all). Sprouting of serotonergic projections near retrogradely labeled phrenic motoneurons were assessed via immunofluorescence, and quantification is in progress. Although we found no evidence that folate supplementation or deprivation impacts diaphragm function following C2Hx, this does not discount folate's potential role in mediating spinal respiratory motor plasticity or functional recovery in other models of CNS injury. For example, C2Hx severs all ipsilateral axons, with a >1mm gap. Since axonal growth and synapse formation is an innately slow process, the duration of this study may not have been sufficient to observe functional recovery mediated via axonal regrowth. Further studies are needed to rule out any role for folate in functional recovery following cervical SCI.Support or Funding InformationMcKnight Brain Institute, NIH SPARC OT 2OD023854, K12 HD055929, NIH T32 HD043730 and HL69064This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.