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Deferoxamine inhibits microglial activation, attenuates blood–brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages
Author(s) -
He Xiaofei,
Lan Yue,
Zhang Qun,
Liu Dongxu,
Wang Qinmei,
Liang Fengying,
Zeng Jinsheng,
Xu Guangqing,
Pei Zhong
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13657
Subject(s) - deferoxamine , posterior parietal cortex , brain damage , medicine , blood–brain barrier , cortex (anatomy) , neuroscience , microglia , pathology , central nervous system , inflammation , immunology , biology
Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine ( DFX ), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57 BL 6 and Thy‐1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two‐photon laser irradiation. DFX (100 mg/kg) was administered 6 h after microhemorrhage induction, followed by every 12 h for three consecutive days. The water maze task was conducted 7 days after induction of microhemorrhages, followed by measurement of blood–brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser‐induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX , supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment.Irons accumulation after intracranial hemorrhage induced a serious secondary damage to the brain. We proposed that irons accumulation after parietal microhemorrhages impaired spatial cognition. After parietal multiple microhemorrhages, increased irons and ferritin contents induced blood–brain barrier disruption, microglial activation, and further induced dendrites loss, eventually impaired the water maze, deferoxamine treatment protected from these damages.