Acute spinal cord injury causes a cascade of multiple cellular and molecular pathways over time.Therefore, therapy aimed at one pathway is unlikely to be successful.To achieve significant breakthroughs in spinal cord neuroprotection and neurorestoration after injury, any intervention must target multiple pathways simultaneously.In present study, we tested the effects of a novel herbal formula on a well-established animal model of spinal cord injury (SCI).The formula administered systemically hours after SCI, and daily thereafter for 3 weeks, significantly improved their locomotor recovery, while simultaneously reducing tissue damage compared to control rats that received only vehicle.RNA microarray screening indicated that the formula-treatment regulated transcription.The formula-treatment significantly altered a number ofgene expressions that are functionally associated with haemostasis, hypoxia response, inflammation/immune responses, signal transduction, tissue and vascular repair.Immunohistochemical analysis for representative proteins corresponded with the changes observed in gene expression patterns on microarray.Immunohistochemical data showed that the formula-treatment significantly enhanced expression of neuroglobin and vascular endothelial growth factor (VEGF).Meanwhile, the formula significantly reduced expression of fibrinogen, Caspase 3, cyclooxygenase-2 (COX2) and Rho A, whereas Growth Associated Protein 43 (GAP43) was increased.Importantly, 21 days after injury nestin was increased by the treatment indicating that the formula also stimulates the intrinsic adult stem/progenitor cells within the injured cords.Thus our data indicate that the formula targets multiple biochemical and cellular pathways not only to effect neuroprotection, but also to enhance neuroregeneration.This lays an objective basis for further studies of the formula leading to its possible consideration for a unique multipletarget approach in future randomized controlled trials in humans with SCI.The outcomes from a few initial cases with chronic traumatic SCI after treated with the herbal formula in Canada are promising.