title: Effectiveness of minocycline in acute white matter injury after intracerebral hemorrhage.
abstract: OBJECTIVE Intracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats. METHODS Thirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and JNK activation were examined. RESULTS In the Fe-injection group, minocycline suppressed WMI labeled by β-amyloid precursor protein (β-APP) and degraded myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were increased after Fe injection, and could be suppressed by minocycline treatment. In the autologous blood-injection group, β-APP and dMBP/MBP levels increased in the ipsilateral site compared with the contralateral site, which could be suppressed by 7 days of minocycline intervention. CONCLUSIONS Iron plays a critical role in WMI after ICH, which can be suppressed by minocycline through reducing the damage induced by Fe.
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Xiang
authors: X
authors: Zou
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Zehan
authors: Z
authors: Wu
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Wei
authors: W
authors: Zhu
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Liang
authors: L
authors: Chen
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Ying
authors: Y
authors: Mao
authors: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors: Fan
authors: F
authors: Zhao
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D056784:Leukoencephalopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D000900:Anti-Bacterial Agents; D004676:Myelin Basic Protein; D008911:Minocycline
keywords: APP = amyloid precursor protein; Fe; GAPDH = glyceraldehyde 3-phosphate dehydrogenase; ICH = intracerebral hemorrhage; JNK = c-Jun N-terminal kinase; MBP = myelin basic protein; WMI = white matter injury; c-Jun N-terminal kinase; dMBP = degraded MBP; intracerebral hemorrhage; iron; minocycline; vascular disorders; white matter injury