High dose methylprednisolone therapy reduces expression of JE/MCP-1 mRNA and macrophage accumulation in the ischemic rat brain

Abstract

The effects of glucocorticoid (GC) on ischemic brain remain to be investigated. Since GC modulates immunological system, it also may inhibit macrophage accumulation in the ischemic brain. The GC effect, if any, on macrophages in ischemic brain, may be mediated through modulation of JE/MCP-1 gene, a strong monocyte attractant, which is expressed in the rat brain after ischemia. The purpose of the present study is to elucidate the effect of high dose methylprednisolone (MP) treatment on (1) macrophage infiltration, (2) histopathology of the ischemic lesion, and (3) expression of JE/MCP-1 mRNA, in a focal cerebral ischemia model of the rat. Thirty Wistar rats were used in this study. Focal cerebral ischemia was induced by advancing a nylon monofilament into the internal carotid artery until the origin of the middle cerebral artery (MCA) was occluded. For JE/MCP-1 mRNA study, animals ( n = 9) were randomly injected with MP 75 mg/kg (×3) ( n = 3), 100 mg/kg (×3) ( n = 3), or same volume of saline ( n = 3) and killed 24 h after onset of MCA occlusion. Three animals were used as a normal control, and a section of the liver from one rat was used as an internal control for JE/MCP-1 mRNA. Northern blot analysis was performed using murine JE c-DNA. For the histopathological study, animals ( n = 17) were randomly divided into a MP group (MP 100 mg/kg × 3, n = 9) and a control group (saline treated, n = 8), and killed 72 h after onset of MCA occlusion. Brain sections were evaluated with hematoxylin-eosin for lesion size, neuronal damage, and inflammatory cell infiltration. Our data demonstrated that the expression of JE/MCP-1 mRNA is reduced after MP treatment of 75 g/kg × 3 and 100 mg/kg × 3 to 65.6% and 14.8% of saline treated animals, respectively. Macrophage infiltration was markedly reduced in the ischemic brain of MP group compared to control group (preoptic area: p < 0.001, other areas: p < 0.05). However, no difference was detected in neuronal damage, neurologic score, and lesion size between the two groups. We conclude that MP treatment reduces the expression of JE/MCP-1 mRNA and markedly attenuates macrophage accumulation in the ischemic brain of rat. However, this treatment does not influence lesion size, neuronal damage, or neurologic outcome of the animals.