Subdural engraftment of serotonergic neurons following spinal hemisection restores spinal serotonin, downregulates serotonin transporter, and increases BDNF tissue content in rat

Spinal hemisection injury at T13 results in development of permanent mechan ical allodynia and thermal hyperalgesia due to interruption and subsequent loss of descending inhibitory modulators such as serotonin (5-HT) and its t ransporter (5-HTT). We hypothesize that lumbar transplantation of non-mitot ic cells that tonically secrete 5-HT and brain-derived neurotrophic factor (BDNF) will restore alterations in 5-HT and 5-HTT systems within the spinal dorsal horn. We used an immortalized rat neuronal cell line, derived from E13 raphe (RN46A-BI4) which is shown to secrete 5-HT and BDNF in vitro and in vivo. Three groups (n=35) of 30 day old male Sprague-Dawley rats were sp inally hemisected at T13 and 28 days later received either lumbar RN46A-V1 control empty-vector (n=15) or RN46A-B14 (n=15) intrathecal grafts, or no t ransplant. Twenty-eight days following transplantation, animals were perfus ed and tissue examined for changes in 5-HT, 5-HTT and BDNF at the site of t ransplantation or at lumbar enlargements (L5). Immunohistochemistry reveale d that RN46A-B14, but not RN46A-V1 cells, increased 5-HT tissue staining at L5 in the dorsal white matter as well as in superficial dorsal horn lamina e I and II on both ipsilateral and contralateral sides, results confirmed b y ELISA. Transplantation of RN46A-B14 cells significantly reduced ipsilater al 5-HTT, upregulated after injury. Significantly increased levels of BDNF were also observed after RN46A-B14 transplantation but were not localized t o particular spinal laminae. These results are consistent with recovery of locomotor function and reductions in chronic pain behaviors observed behavi orally after RN46A-B14 transplantation and supports the pragmatic applicati on of cell-based therapies in correcting damaged circuitry after spinal cor d injury. (C) 2001 Published by Elsevier Science B.V.