Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages
| Autor: | Qinmei Wang, Zhong Pei, Xiao-fei He, Jinsheng Zeng, Qun Zhang, Dong-xu Liu, Feng-ying Liang, Yue Lan, Guang-qing Xu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse Pathology medicine.medical_specialty Iron Overload Iron Siderophores Posterior parietal cortex Mice Transgenic Water maze Brain damage Deferoxamine Blood–brain barrier Biochemistry Pathogenesis 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Animals Medicine Cerebral Hemorrhage Spatial Memory biology business.industry Dendrites Mice Inbred C57BL Ferritin Disease Models Animal 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier biology.protein medicine.symptom business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neurochemistry. 138:436-447 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.13657 |
| Popis: | 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. C57BL6 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. |
| Databáze: | OpenAIRE |
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