Previous studies have shown that prevention of leukocyte infiltration by targeting integrins involved in transendothelial migration may suppress the clinical and pathological features of neuroinflammatory disease. This study was designed to investigate the effects of C16, an ανβ3 integrin-binding peptide, in an acute experimental allergic encephalomyelitis (EAE) rat model. Multiple histological and immunohistochemical staining, electron microscopy observation, ELISA assay, Western blot, and magnetic resonance imaging (MRI) were employed to assess the degree of inflammation, axonal loss, neuronal apoptosis, white matter demyelination, and extent of gliosis in the brain and spinal cord of differently treated EAE models. The results showed that C16 treatment could inhibit extensive leukocyte and macrophage accumulation and infiltration and reduce cytokine tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) expression levels. A significantly lower clinical score at the peak time of disease was also demonstrated in the C16 treated group. Moreover, astrogliosis, demyelination, neuronal death, and axonal loss were all alleviated in C16 treated EAE animals, which may be attributed to the improvement of microenvironment. The data suggests that C16 peptide may act as a protective agent by attenuating inflammatory progression and thus affecting the expression of some proinflammatory cytokines during neuroinflammatory disease. 1. Introduction Multiple Sclerosis (MS) is a progressive autoimmune disease that invokes an inflammatory attack on the central nervous system (CNS) resulting in an accumulating disability [1, 2]. Experimental allergic encephalomyelitis (EAE) is a primary animal model of MS which is widely used for the evaluation of different drugs in MS treatment [3]. EAE includes the breakdown of the blood-brain barrier, infiltration of the CNS by CD4 T cells and macrophages, and activation of microglia and astrocytes. This results in inflammation followed by demyelination [1, 4, 5]. Activated microglia and astrocytes have been implicated in the secretion of a number of proinflammatory mediators, such as TNF-α, IFN-γ, and metalloproteinases, which act as inflammatory mediators and tissue damaging agents in the onset of EAE [1, 6, 7]. The remission phase of EAE is accompanied by increased production of immunoregulatory cytokine transforming growth factor-β (TGF-β) [8, 9]. As the disease progresses, defective remyelination due to the loss of oligodendrocytes and axonal degeneration can lead to the increase of clinical handicaps [10]. In addition to that,
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