Effects of atorvastatin in the regulation of circulating EPCs and angiogenesis in traumatic brain injury in rats

Abstract

Circulating endothelial progenitor cells (EPCs) play an important role in angiogenesis and vasculogenesis. Statins administered promote functional improvement in rats, independent of their capability to lower cholesterol. Whether statin treatment regulates circulating EPCs after traumatic brain injury (TBI) has not been investigated. We hypothesized that atorvastatin increases circulating EPCs and promotes angiogenesis in TBI rats. Wistar rats (20 months old) were subjected to TBI and treated with or without atorvastatin (orally administered, 1mg/kg/day) starting 1h after TBI and then daily for 14 consecutive days. Long term potentiation (LTP) in the cornu ammonis1 of the hippocampus as well as the Modified Neurological Severity Score (mNSS) and the Morris Water Maze (MWM) functional tests were performed. Blood circulating EPCs were identified by flow cytometry. Rats were sacrificed 25 days after TBI. vWF and CD31 immunostaining was performed. We found that atorvastatin administration significantly induced angiogenesis and increased circulating EPC levels as well as improved functional recovery when compared with non-treatment TBI-control rats (P<0.05). The circulating EPC level is correlated with vascular density (r=0.878, P <0.05) and CD31 positive cell number in the injured brain (r=0.921, P <0.05). The results suggest that increasing circulating EPCs with atorvastatin treatment may contribute to the observed increase in angiogenesis and improved functional outcome after TBI.