J Neurotrauma. 2009 May 26.

Neuronal apoptosis inhibited by cord blood stem cells after spinal cord injury.

Dasari VR, Veeravalli KK, Tsung AJ, Gondi CS, Gujrati M, Dinh D, Rao JS.

University of Illinois College of Medicine, Cancer Biology and Pharmacology, Peoria, Illinois, United States; rdasari@uic.edu.

Spinal cord injury (SCI) induces a series of endogenous biochemical changes, which lead to secondary damage involving apoptosis as one of the major events. To understand the molecular basis of apoptosis after spinal cord injury, we subjected male rats to spinal cord injury using NYU impactor and evaluated the therapeutic potential of human umbilical cord blood stem cells (hUCB), which were stereotactically transplanted into the injury epicenter one week after SCI. We identified genes that render the adult-injured spinal cord non-conducive and the hUCB-treated spinal cord conducive to regeneration and repair at 3 weeks using RT-PCR microarray by analyzing 84 apoptotic genes. Genes involved in inflammation and apoptosis were upregulated in injured spinal cords of rats, whereas genes involved in neuroprotection were upregulated in the hUCB-treated rats. Quantitative real time PCR verified mRNA changes in the apoptotic genes of TNF-alpha, TNFR1, TNFR2, Fas, Lta and CD40. Based on these results, we evaluated the role of TNF-alpha and its related apoptotic genes in neuronal death after spinal cord injury. Changes in the expression of TNF-alpha, TNFR1 and TNFR2 were observed over a period of 3 weeks SCI and after treatment with hUCB. Expression of P50 and P65 on neurons after SCI was efficiently downregulated by hUCB. These results were confirmed by the evaluation of apoptotic proteins of cocultures of spinal neurons with hUCB under in vitro conditions. This study suggests the therapeutic potential of hUCB in inhibiting the neuronal apoptosis during the repair of injured spinal cord.