Lack of dystrophin results in abnormal cerebral diffusion and perfusion in vivo.

Dystrophin, the main component of the dystrophin-glycoprotein complex, plays an important role in maintaining the structural integrity of cells. It is also involved in the formation of the blood-brain barrier (BBB). To elucidate the impact of dystrophin disruption in vivo, we characterized changes in cerebral perfusion and diffusion in dystrophin-deficient mice (mdx) by magnetic resonance imaging (MRI). Arterial spin labeling (ASL) and diffusion-weighted MRI (DWI) studies were performed on 2-month-old and 10-month-old mdx mice and their age-matched wild-type controls (WT). The imaging results were correlated with Evan's blue extravasation and vascular density studies. The results show that dystrophin disruption significantly decreased the mean cerebral diffusivity in both 2-month-old (7.38 ± 0.30 × 10(-4)mm(2)/s) and 10-month-old (6.93 ± 0.53 × 10(-4)mm(2)/s) mdx mice as compared to WT (8.49 ± 0.24 × 10(-4), 8.24 ± 0.25 × 10(-4)mm(2)/s, respectively). There was also an 18% decrease in cerebral perfusion in 10-month-old mdx mice as compared to WT, which was associated with enhanced arteriogenesis. The reduction in water diffusivity in mdx mice is likely due to an increase in cerebral edema or the existence of large molecules in the extracellular space from a leaky BBB. The observation of decreased perfusion in the setting of enhanced arteriogenesis may be caused by an increase of intracranial pressure from cerebral edema. This study demonstrates the defects in water handling at the BBB and consequently, abnormal perfusion associated with the absence of dystrophin.