Apamin as a BBB Shuttle and Its Effects on T Cell Population During the Experimental Autoimmune Encephalomyelitis-Induced Model of Multiple Sclerosis.

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system presented by autoimmune manifestations. This study aimed at investigating the effects of apamin administration on the activated T cell population in an experimental autoimmune encephalomyelitis (EAE) MS model. Thirty mice underwent EAE induction and were then randomly divided into 5 groups. Three groups received 10, 50, and 100\xa0µg/kg apamin; the fourth group received 1\xa0mg/kg dexamethasone; and the fifth group received the equivalent amount of PBS (phosphate-buffered saline) intraperitoneally. Peripheral CD4\u2009+\u2009cell and memory T cell distribution was measured with a flow cytometer every week. Also, CD4\u2009+\u2009and CD8\u2009+\u2009cell infiltration to the brain was assessed with immunohistochemistry. It was observed that the group receiving 50\xa0µg/kg apamin had a lower EAE score in comparison with the groups receiving 100\xa0µg/kg apamin (p 0.014). Also, peripheral blood memory cells with CD44\u2009+\u2009, CD62L\u2009-\u2009, and CD4\u2009+\u2009markers were decreased in apamin-administered groups. Regarding the infiltrated CD8\u2009+\u2009cells, a significant decrease (p 0.002) was observed in the group receiving 50\xa0µg/kg apamin compared with the control group. These results indicate that 50-µg/kg doses of apamin had an effective treatment over 14\xa0days; it reduced both the severity of symptoms and the infiltration of CD8\u2009+\u2009cells into the CNS. Moreover, it increased myelin density and decreased the circulation of CD62L\u2009-\u2009, CD44L\u2009-\u2009, and CD44\u2009+\u2009memory T cells. So, it appears that apamin plays a critical role in regulating immunity and reducing the complications of autoimmune MS.