Treatment with the neurosteroid dehydroepiandrosterone promotes recovery of motor behavior after moderate contusive spinal cord injury in the mouse

Abstract

The neurosteroid dehydroepiandrosterone (DHEA) has neuroprotective properties after ischemic and excitatory insults to the brain. In the developing embryo, it is produced in discrete regions of the central nervous system (CNS), where it specifically promotes axonal growth of differentiated neurons. To test if DHEA could be beneficial after spinal cord injury (SCI), we used a model of moderate contusive SCI developed and characterized in the mouse. Immediately after surgery, we applied treatment with DHEA or with vehicle only and compared treatment groups (n = 12 in each group) over a 42-day period. Locomotor recovery was assessed in an open field using a standardized 21-point scale, according to gait analysis on paw print recordings and using foot fault analyses on an inclined ladder beam. The DHEA-treated group showed improved function compared to vehicle-treated animals in these tests. More strikingly, DHEA enhanced recovery of left-right coordination and fine motor control. In an attempt to correlate functional recovery with spinal cord neuropathology in the different experimental groups, we studied the area of spared white matter at the epicenter and reactive gliosis/scar formation 42 days post-injury (DPI). DHEA significantly increased the area of white matter spared at the epicenter and reduced the area of reactive gliosis surrounding the lesion. These data demonstrate the effectiveness of DHEA in promoting functional recovery in the adult murine injured spinal cord.