The Effect of Micro-Particles of Linoleic Acid Emulsion on the Blood-Brain Barrier in Cats

ABSTRACT

PURPOSE: The purpose of this study was to investigate the permeability change of the blood-brain barrier and the reversibility of the embolized lesions induced with a fat-emulsion technique by using magnetic resonance imaging (MRI), and we also wished to evaluate the resultant histologic findings in cat brains. MATERIALS AND METHODS: MR imaging was scheduled serially at 1 hour, day 1, day 4 and day 7 after infusion of linoleic acid-emulsion (0.05 ml linoleic acid+20 ml saline) to the internal carotid artery in 12 cats. Abnormal signal intensity or contrast enhancement was evaluated on diffusion-weighted images (DWIs), the apparent diffusion coefficient (ADC) maps, and gadolinium-enhanced T1-weighted images (Gd-T1WIs) at the stated times. MR imaging was stopped if the lesion shows isointensity and no contrast enhancement was observed at the acquisition time, and then brain tissue was harvested and examined. Light microscopic (LM) and electron microscopic (EM) examinations were performed. RESULTS:The embolized lesions appeared as isointensities (n=7) or mild hyperintensities (n=5) on DWIs, as isointensities (n=12) on the ADC maps, and as contrast enhancements (n=12) on Gd-T1WIs at 1 hour. The lesions showed isointensity on DWIs and the ADC maps, and as no contrast enhancement for all cats at day 1. The LM findings revealed small (< 1 cm) focal necrosis and demyelination in three cats. EM examinations showed minimal findings of small (< 3 micrometer) fat globules within the endothelial wall (n=10) and mild swelling of the neuropils (< 5 micrometer). Widening of the interstitium or morphologic disruption of the endothelial wall was not seen. CONCLUSION: Cerebral fat embolism induced by linoleic acid emulsion revealed vasogenic edema and reversible changes as depicted on the MR images. These results might help us to understand the mechanisms of fat on the blood-brain barrier, and this technique could be used as a basic model for research of the effects of drugs on the disrupted blood-brain barrier, and also as a research model for the chemotherapeutic effects of drugs of the brain tumors.