Improved functional recovery following spinal cord compression in rats treated with losartan is associated with reduced T cell influx into the injury site

Abstract

Inhibition of the renin‐angiotensin system (RAS) is neuroprotective in a variety of CNS disorders, including Parkinson disease, Alzheimer disease and stroke. One proposed mechanism for protective effects of RAS inhibition is modulation of inflammation. Post‐injury inflammation has been implicated in degenerative cascades initiated by mechanical trauma to the spinal cord, thus we sought to determine whether a similar protective effect of RAS inhibition would occur following spinal cord injury (SCI). Rats were treated with losartan or vehicle (i.p., sid), beginning one day after lateral compression SCI. Functional recovery was assessed using a standardized scale. Rats were sacrificed at 7, 14 or 28 days post injury (dpi) and the tissues processed for PCR or immunohistochemical analyses. We show that rats treated with losartan have improved functional recovery compared to vehicle‐treated rats, beginning at 5 dpi. Quantitative PCR revealed that treatment with losartan decreased the intraspinal expression of CCL5, a chemokine that promotes T cell infiltration into tissues. Decreased expression of CCL5 was associated with a significant decrease in the number of T cells within the injury site at 7 dpi and maintained to 28 dpi. Collectively, these data suggest that beneficial effects of RAS inhibition in this spinal cord injury model may be due to a reduction in the T cell response within the injury site.This study was supported by MWU Office of Research and Sponsored Programs (E.R., A.H‐D.), MWU College of Health Sciences (CBJ), and Arizona College of Osteopathic Medicine (TBJ).