Effects of statin and deferoxamine administration on neurological outcomes in a rat model of intracerebral hemorrhage

被引:32
作者
Chun, Hyoung-Joon [2 ]
Kim, Dong Won [1 ]
Yi, Hyeong-Joong [2 ]
Kim, Young Soo [2 ]
Kim, Eun Hyun [3 ]
Hwang, Se Jin [3 ]
Jwa, Cheol-Su [4 ]
Lee, Yoon Kyoung [5 ]
Ryou, Hyunchul [6 ]
机构
[1] Hanyang Univ, Med Ctr, Dept Anesthesiol & Pain Med, Seoul 133792, South Korea
[2] Hanyang Univ, Med Ctr, Dept Neurosurg, Seoul 133792, South Korea
[3] Hanyang Univ, Dept Anat & Cell Biol, Seoul 133792, South Korea
[4] Natl Med Ctr, Dept Neurosurg, Seoul, South Korea
[5] Redcross Coll, Dept Nursing, Seoul, South Korea
[6] Wonjin Green Hosp, Dept Occupat & Environm Med, Seoul, South Korea
关键词
Deferoxamine; Inflammation; Intracerebral hemorrhage; Iron; Neuroprotection; Statin; BRAIN EDEMA; INJURY; BLOOD; IRON; CYCLOOXYGENASE-2; DEATH;
D O I
10.1007/s10072-011-0733-y
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Deferoxamine (DFX), a potent iron-chelating agent, reduces brain edema and neuronal cell injury that develop due to the hemolysis cascade. Statins have neuroprotective effects via anti-inflammatory action and increment of cerebral blood flow after intracerebral hemorrhage (ICH). The purpose of this study was to identify the effects of combined DFX and statins treatment in an experimental ICH rat model. The treatments were: intraperitoneal (i.p.) injection of DFX (group I), combined treatment of i.p. DFX and oral statins (group II), statins only (group III) and treatment with vehicle (group IV). Induction of ICH was performed with injection of bacterial collagenase type IV into the left striatum. After removal of the brain, hematoma volume, water content and brain atrophy were measured. Immunohistochemistry in the perihematomal region was performed for identification of microglial infiltration, astrocyte expression and apoptotic cell presence. Statistical analysis was performed using the non-parametric Kruskal-Wallis test and significance was evaluated when the p value was less than 0.05. According to behavioral tests, significant differences among treatment groups were noted 4 weeks after ICH induction (p < 0.05). However, there were no significant differences among treatment groups in hematoma volume, brain water content or brain atrophy. In the perihematomal area, the activated microglial cells were reduced in the combined treatment group. Among the four groups, a significant difference in immunohistochemical staining was identified (p < 0.05). These results suggest that combined treatment with DFX and statins improves neurologic outcomes after ICH through reduction of microglial infiltration, apoptosis, inflammation and brain edema.
引用
收藏
页码:289 / 296
页数:8
相关论文
共 23 条
[1]
Cappellini Maria D, 2009, Hemoglobin, V33 Suppl 1, pS58, DOI 10.3109/03630260903346924
[2]
Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke [J].
Chen, JL ;
Zhang, ZG ;
Li, Y ;
Wang, Y ;
Wang, L ;
Jiang, H ;
Zhang, CL ;
Lu, M ;
Katakowski, M ;
Feldkamp, CS ;
Chopp, M .
ANNALS OF NEUROLOGY, 2003, 53 (06) :743-751
[3]
Deferoxamine Reduces Intracerebral Hematoma-Induced Iron Accumulation and Neuronal Death in Piglets [J].
Gu, Yuxiang ;
Hua, Ya ;
Keep, Richard F. ;
Morgenstern, Lewis B. ;
Xi, Guohua .
STROKE, 2009, 40 (06) :2241-2243
[4]
Behavioral tests after intracerebral hemorrhage in the rat [J].
Hua, Y ;
Schallert, T ;
Keep, RF ;
Wu, JM ;
Hoff, JT ;
Xi, GH .
STROKE, 2002, 33 (10) :2478-2484
[5]
HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage [J].
Jung, KH ;
Chu, K ;
Jeong, SW ;
Han, SY ;
Lee, ST ;
Kim, JY ;
Kim, M ;
Roh, JK .
STROKE, 2004, 35 (07) :1744-1749
[6]
HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats [J].
Kawashima, S ;
Yamashita, T ;
Miwa, Y ;
Ozaki, M ;
Namiki, M ;
Hirase, T ;
Inoue, N ;
Hirata, K ;
Yokoyama, M .
STROKE, 2003, 34 (01) :157-163
[7]
Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage [J].
Nakamura, T ;
Keep, RF ;
Hua, Y ;
Schallert, T ;
Hoff, JT ;
Xi, GH .
JOURNAL OF NEUROSURGERY, 2004, 100 (04) :672-678
[8]
Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia [J].
Nogawa, S ;
Forster, C ;
Zhang, FG ;
Nagayama, M ;
Ross, ME ;
Iadecola, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (18) :10966-10971
[9]
Deferoxamine Treatment for Intracerebral Hemorrhage in Aged Rats Therapeutic Time Window and Optimal Duration [J].
Okauchi, Masanobu ;
Keep, Richard F. ;
Morgenstern, Lewis B. ;
Schallert, Timothy ;
Xi, Guohua .
STROKE, 2010, 41 (02) :375-382
[10]
Effects of Deferoxamine on Intracerebral Hemorrhage-Induced Brain Injury in Aged Rats [J].
Okauchi, Masanobu ;
Hua, Ya ;
Keep, Richard F. ;
Morgenstern, Lewis B. ;
Xi, Guohua .
STROKE, 2009, 40 (05) :1858-1863