Impact of arginase II on CBF in experimental cortical impact injury in mice using MRI

Abstract

Traumatic brain injury (TBI) results in reduced cerebral blood flow (CBF) and low levels of the vasodilator nitric oxide (NO) may be involved. Arginase II negatively regulates NO production through competition for the substrate L-arginine. We determined whether arginase II-deficient (ArgII(-/-)) mice would show improved CBF after TBI through arterial spin-labeling magnetic resonance imaging (MRI). The ArgII(-/-) mice exhibit a significantly improved CBF recovery after trauma in the perilesional brain (P=0.0015) and in various other brain regions. In conclusion, arginase II deficiency leads to a better CBF recovery after TBI and implicates arginase II in hemodynamic processes.

Figure 1

Regions of interest (ROIs) for cerebral blood flow (CBF) calculations. (A–C) Regions of interest and CBF maps for arterial spin labeling (ASL) MRI mouse brain scans. (A) Coronal brain slice used for CBF measurements. (B) Six ROIs were used to determine CBF, three from each hemisphere. Regions contralateral and ipsilateral to the traumatic brain injury (TBI) (indicated by the red arrow) were chosen in the cortex, subcortex, and striatum. (C) Cerebral blood flow map of an arginase II-deficient (ArgII^−/−) mouse and a wild-type (WT) mouse before TBI, 15 minutes after TBI, and 1 hour after TBI. The ArgII^−/− mice show less CBF blunting and/or better CBF recovery. Maps were created by applying the relative CBF (rCBF) equation (rCBF = λ × 60,000 × ((1/T_1(selective))−(1/T_{1(nonselective)})) to T₁ maps of the brain created from the ASL scans. A color map was applied. Relative CBF units: mL/100 g/minute. Red arrows indicate the site of TBI impact.