Enhanced antioxidant enzyme expression in inflammatory multiple sclerosis lesions

Reactive oxygen species (ROS) contribute to the formation and persistence of multiple sclerosis (MS) lesions by acting on distinct pathological processes. In the initial phase of MS lesion development, locally produced ROS may induce blood-brain barrier disruption and enhance leukocyte migration and myelin phagocytosis. In advanced stages, ROS may contribute to lesion persistence by mediating oligodendroglial damage and axonal injury. Generally, high levels of ROS cause oxidative stress, which induces transcription of antioxidant response element (ARE)-regulated genes. These genes encode various endogenous antioxidant enzymes that confer protection against oxidative damage. Here, we studied the expression of endogenous antioxidant enzymes in control brain tissue and various stages of MS lesions. ARE-regulated antioxidant enzymes, including superoxide dismutase-1 and -2, catalase, peroxiredoxin-1 and heme oxygenase-1 are expressed by glial cells in white matter from control brains and normal appearing white matter. Interestingly, these cytoprotective antioxidant enzymes are markedly upregulated in active demyelinating MS lesions. Particularly, foamy macrophages containing myelin and cellular debris and hypertrophic astrocytes abundantly expressed endogenous antioxidant enzymes. We speculate that enhanced antioxidant enzyme production in inflammatory MS lesions indicates the occurrence of oxidative stress and may reflect an adaptive defense mechanism to counteract ROS-induced cellular damage.