Acute administration of AMPA/Kainate blocker combined with delayed transplantation of neural precursors improves lower urinary tract function in spinal injured rats

To evaluate bladder function recovery after spinal cord injury (SCI) in response to a combination treatment of an acutely administered AMPA/kainate receptor antagonist and delayed transplantation of neuronal precursors. Female rats received a contusion injury at T8/9. The AMPA/kainate receptor antagonist NBQX was directly administered into the lesion site immediately after injury. Nine days post-injury, NRP/GRP were delivered into the lesion site. Controls received NRP/GRP grafts only or no treatment (OP-Controls). Animals underwent bladder function testing during the course of the experiment and at the endpoint. Motor function was evaluated as well. After sacrifice, histological analysis of lesion site and lumbosacral spinal cord regions was performed. Rats receiving the combined treatment (NBQX&NRP/GRP) had voided volumes/micturition resembling that of normal animals and showed greater improvement of urodynamic parameters, compared to NRP/GRP alone or OP-Controls. Similarly, NBQX&NRP/GRP induced more spouting, regeneration or sparing of descending projections to the lumbosacral cord. The density of primary afferent projections at the lumbosacral spinal cord in rats with combined treatments was similar to that of NRP/GRP alone with decreased sprouting of primary afferents in lumbosacral cord, compared to OP-Control. Immunohistochemical evaluation revealed that the combined treatment reduced the size of the lesion to a greater extent than NRP/GRP alone or OP-Controls. NRP/GRP with and without NBQX produced a significant recovery of hindlimb compared to OP-Controls. In conclusion, transplants of NRP/GRP combined with NBQX promote recovery of micturition function following spinal cord injury, likely through increased neuroprotection.

► NBQX&NRP/GRP accelerated recovery of bladder contraction from spinal shock.
► NBQX and neural precursors improved cystometric parameters in SCI.
► NBQX and neural precursors protected host spinal tissue in SCI.
► NBQX and NRP/GRP induced descending projections to the lumbosacral cord.
► NBQX&NRP/GRP inhibited sprouting of primary afferents in lumbosacral cord.