title: Charting the course of renal cryoinjury.
abstract: We sought to characterize a minor renal cryoinjury that allows investigation into renal damage processes and subsequent endogenous repair mechanisms. To achieve this, we induced a small cryoinjury to mice, in which the transient superficial application of a liquid nitrogen-cooled cryoprobe to the exposed kidney induces a localized lesion that did not impair renal function. The resulting cryoinjury was examined by immunohistochemistry and Laser-Doppler flowmetry. Within hours of cryoinjury induction, tubular and vascular necrotic damage was observed, while blood flow in the directly injured area was reduced by 65%. The injured area demonstrated a peak in tubular and perivascular cell proliferation at 4 days postinjury, while apoptosis and fibrosis peaked at day 7. Infiltration of macrophages into the injury was first observed at day 4, and peaked at day 7. Vascular density in the direct injured area was lowest at day 7. As compared to the direct injured area, the (peripheral) penumbral region surrounding the directly injured area demonstrated enhanced cellular proliferation (2.5-6-fold greater), vascular density (1.6-2.9 fold greater) and blood perfusion (twofold greater). After 4 weeks, the area of damage was reduced by 73%, fibrosis decreased by 50% and blood flow in the direct injured area was reestablished by 63% with almost complete perfusion restoration in the injury's penumbral region. In conclusion, kidney cryoinjury provides a flexible facile model for the study of renal damage and associated endogenous repair processes.
authors.affiliation: Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York, USA Department of Pathology, Renal Research Institute, New York Medical College, Valhalla, New York, USA.
authors.forename: Wasan
authors.initials: W
authors.lastname: Abdulmahdi
authors.affiliation: Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Zullo
authors.affiliation: Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Nesi
authors.affiliation: Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York, USA Department of Pharmacology, Renal Research Institute, New York Medical College, Valhalla, New York, USA Department of Physiology, Renal Research Institute, New York Medical College, Valhalla, New York, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Goligorksy
authors.affiliation: Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York, USA Department of Physiology, Renal Research Institute, New York Medical College, Valhalla, New York, USA Ratlifbb@gmail.com.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Ratliff
keywords: Apoptosis proliferation; cryoinjury; kidney injury model; renal blood perfusion