title: Minocycline-induced attenuation of iron overload and brain injury after experimental germinal matrix hemorrhage.
abstract: Germinal matrix hemorrhage (GMH) is the most important adverse neurologic event during the newborn period. Evidence has shown that neonates with GMH and hydrocephalus have more severe damage compared to those with GMH alone. Our preliminary study demonstrated the role of iron in hydrocephalus and brain damage in adult rats following intraventricular hemorrhage. Therefore, the aim of the current study was to investigate iron accumulation and iron-handling proteins in a rat model of GMH and whether minocycline reduces iron overload after GMH and iron-induced brain injury in vivo. This study was divided into two parts. In the first part, rats received either a needle insertion or an intracerebral injection of 0.3 U of clostridial collagenase VII-S. Brain iron and brain iron handling proteins (heme oxygenase-1 and ferritin) were measured. In the second part, rats with a GMH were treated with minocycline or vehicle. Brain edema, brain cell death, hydrocephalus, iron-handling proteins and long-term motor function were examined. The result showed iron accumulation and upregulation of iron-handling proteins after GMH. Minocycline treatment significantly reduced GMH-induced brain edema, hydrocephalus and brain damage. Minocycline also suppressed upregulation of ferritin after GMH. In conclusion, the current study found that iron plays a role in brain injury following GMH and that minocycline reduces iron overload after GMH and iron-induced brain injury.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yihao
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zhichen@tmmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001929:Brain Edema / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019190:Iron Overload / Q000209:etiology*; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline
keywords: Ferritin; Germinal matrix hemorrhage; Iron; Minocycline