백서 뇌출혈 모델에서 스타틴과 디페록사민의 투여가 신경학적인 예후에 미치는 영향

Abstract

Deferoxamine (DFX), a potent iron chelating agent, reduces the brain edema, neuronal cell injury, brain atrophy developed from hemolysis cascade, and statins have neuroprotective effects via anti-inflammatory action and increase cerebral blood flow after intracerebral hemorrhage (ICH). The purpose of the present study is to identify the effects of the combined treatment with DFX and statins compared with individual treatments in experimental ICH rat model using neurologic scale and various immunohistochemistry and histology. The present study was designed with four groups as followings (n=11 per each group); intraperitoneal (i.p.) injection of DFX (group &#1030; ), Combined treatment with i.p. DFX and oral statins (group Ⅱ), statins administration only (group Ⅲ), and vehicle treatment (group Ⅳ). Induction of ICH was performed with injection of 0.23 U of bacterial collagenase type Ⅳ into the left striatum. On each group, seven rats were sacrificed after 3 days administration of drugs, and 4 rats after behavioral test such as modified limb placing test and corner turn test during 6 weeks following ICH induction. After removal of the brain, hematoma volume, water content, and brain atrophy was measured. Immunohistochemistry with OX-42 for microglial infiltration, glial fibrillary acidic protein (GFAP) for astrocyte expression, and caspase-3 for apoptotic cell in the perihematomal region were also performed in brain sections and the degree of immunohistochemical expression was measured with optical intensity. The statistical analysis was performed with non-parametric Kruskal-Wallis test, and significance was evaluated when p value was less than 0.05. According to behavioral test, statistical significance was noted 4 weeks after ICH induction. (p<0.05) However, there was no statistical difference in hematoma volume (p=0.170), brain water content (p=0.170) and brain atrophy (p=0.433). In the perihematomal area, although the activated microglial cells were reduced in the combined treatment group compared with individual treated groups, the expression of apoptotic cells and astrocyte was similar or more in the combination therapy group than statin only treated group. Among 4 groups, statistical significance was identified as p<0.05 in the immunohistochemical staining. These results show that combined treatment with DFX and statins improves neurologic outcome after ICH induction through reduction of microglial infiltration, apoptosis, inflammation process, and brain edema. Although author cannot directly compares between combined treatment and individual treatments due to small specimen, combined treatment may be useful for ICH management with different mechanism via suppression of inflammatory process by statins and iron chelating action by DFX. To clarify the effectiveness of combination treatment compared with alone treatment, further investigation is needed with large cohort.