Society for Neuroscience Chicago 2015
Spinal Cord Injury: Animal Models and Human Studies Trauma
Support: VARRD The Gordon Project to Cure Clinical Paralysis
Title: Evoked potential analysis of hMSC and anastomosis mediated functional recovery for chronic thoracolumbar SCI
Abstract: We previously reported that anastomosis/neurotization could significantly improve locomotion in rats with thoracolumbar contusion spinal cord injury (SCI). The benefits included enhancing coordinated hindlimb functions of open field locomotion and incline plane performance, and sensorimotor recoveries evaluated by spinal reflex tests. Post-neurotization recovery neurobiology mechanisms comprised enrichment of intraspinal cord synapses and strengthened propriospinal projection connectivity across the contusion site. To further assess specific neural circuit(s) involved in locomotion recovery, we performed a pilot study on evoked potentials in chronic SCI rats that demonstrated persistent locomotion improvement (i.e., ≥ 12 months) following neurotization treatment. Briefly, female SD rats (220-235g) received T13-L1 moderate contusion (10gx25mm) and T12-L3 neurotization at either 1 week (subacute) or 13 weeks (chronic) after SCI (n=4/each study). For rats with chronic SCI, neurotization was done 710 days following human mesenchymal stromal stem cell (hMSC) injection (50K cells/µl; 1µl injection at 1 mm rostral and caudal to the epicenter, respectively and 2µl into the injury site; total: 200K cells/rat; n=4/group). Behavior tests were performed weekly for 10 months in order to confirm sustainability of locomotion recovery. Based on our previous finding, we hypothesized that the regained locomotion capability might be partially facilitated by serotonergic modulation. We therefore administered 5-HT1A and 2A/2C agonists and/or antagonists intraperitoneally or intrathecally to examine their effects on hindlimb function.
The results replicated data we reported before, showing that the locomotion recovery could be additionally boosted by treatment with 5-HT1A and 2A/2C agonists acting specifically via corresponding receptors. We next measured cortical motor evoked or peripheral nerve (C7) evoked potentials (EPs) recorded at loci either rostral (T6-T7) or caudal (L3-L4) to the injury epicenter to determine which neural circuit(s) contributed to reactivation of the central pattern generation (CPG). The EP outcomes, together with neural tracing data, suggest that T12-L3 neurotization following hMSC implantation provides a multimodal approach to functional recovery for chronic thoracolumbar contusion SCI.
(Supported by VARRD and the Gordon Project to Cure Clinical Paralysis) Disclosures: X. Zeng: None. D. Yu: None. J.E. Anderson: None. Z. Aljuboori: None. R.D. Zafonte: None. Y.D. Teng: None.
Authors: *X. ZENG1,2, D. YU1,2, J. E. ANDERSON1,2, Z. ALJUBOORI1,2, R. D. ZAFONTE3, Y. D. TENG1,2,3; 1Dept. of Neurosurg., Brigham & Women’s Hospital/Harvard Med. Sch., Boston, MA; 2Div. of SCI Res., VA Boston Healthcare Syst., Boston, MA; 3Physical Med. and Rehabil., Spaulding Rehabil. Hospital/Harvard Med. Sch., Boston, MA