The role of dietary antioxidant insufficiency on the permeability of the blood-brain barrier.

Our previous studies implicated vitamin E deficiency as a risk factor for equine motor neuron disease, a possible model of human amyotrophic lateral sclerosis, and showed direct effects of this deficiency on brain vascular endothelium. To gain better understanding of the pathogenesis of equine motor neuron disease, we determined the effects of dietary antioxidant insufficiency and the resultant brain tissue oxidative stress on blood-brain barrier permeability. Rats (n = 40) were maintained on a diet deficient of vitamin E for 36 to 43 weeks; 40 controls were fed a normal diet. Permeability of the blood-brain barrier in the cerebral cortex was investigated using rhodamine B, and lipid peroxidation was measured as a marker for oxidative stress. Animals on the vitamin E-deficient diet showed less weight gain and had higher brain lipid peroxidation compared with the controls. Fluorometric studies demonstrated greater rhodamine B in the perivascular compartment and central nervous system parenchyma in rats on the deficient diet compared with controls. These results suggest that a deficiency in vitamin E increases brain tissue oxidative stress and impairs the integrity of the blood-brain barrier. These observations may have relevance to the pathogenesis of amyotrophic lateral sclerosis and other neurologic diseases.