Premium
The effects of angiotensin receptor blockade on functional recovery and inflammatory gene expression following spinal cord injury
Author(s) -
Robbins Emily A,
Shlifer I. G.,
Manning D.,
Jones C. B.,
Jones T. B.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.921.3
Subject(s) - losartan , neuroinflammation , spinal cord injury , inflammation , medicine , captopril , angiotensin ii , renin–angiotensin system , angiotensin receptor , spinal cord , pharmacology , endocrinology , receptor , blood pressure , psychiatry
The role of the renin‐angiotensin system (RAS) in inflammation has been documented. However, its effect on neuroinflammation following spinal cord injury (SCI) has not yet been studied. We sought to evaluate the effect of inhibiting RAS on recovery of function and markers of inflammation following SCI. Female, Sprague‐Dawley rats were treated with losartan (angiotensin II type 1 receptor (AT1R) blocker), captopril (angiotensin converting enzyme (ACE) inhibitor) or vehicle ( i.p., sid ), beginning one day after lateral compression SCI. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Locomotor Rating 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 or captopril have improved functional recovery compared to vehicle‐treated rats. Quantitative PCR array revealed the expression of AT1R and AT2R in the spinal cords of injured and uninjured rats and the induction of pro‐inflammatory genes over 28 dpi. AT1R appears to be localized to infiltrating immune cells following SCI. These data indicate that manipulation of RAS by blocking AT1R or ACE improves functional recovery and causes changes in gene expression in rats following SCI. Thus, further exploration of therapeutic intervention of RAS following SCI appears warranted. Grant Funding Source : Office of Research and Sponsored Programs ‐ Midwestern University