Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages.

Abstract

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.

• Authors: Xiao-Fei He, Yue Lan, Qun Zhang, Dong-Xu Liu, Qinmei Wang, Feng-Ying Liang, Jin-Sheng Zeng, Guang-Qing Xu, Zhong Pei
• Journal: Journal of neurochemistry (J Neurochem) Vol. 138 Issue 3 Pg. 436-47 (08 2016) ISSN: 1471-4159 [Electronic] England
• PMID: 27167158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 International Society for Neurochemistry.

Chemical References

• Siderophores
• Iron
• Deferoxamine

Topics

• Animals
• Blood-Brain Barrier (drug effects, metabolism)
• Cerebral Hemorrhage (drug therapy, pathology)
• Deferoxamine (pharmacology)
• Dendrites (drug effects, metabolism)
• Disease Models, Animal
• Iron (metabolism)
• Iron Overload
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Siderophores (pharmacology)
• Spatial Memory (drug effects)