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Enhanced oxidative stress contributes to worse prognosis and delayed neurofunctional recovery after striatal intracerebral hemorrhage in 5XFAD mice
Author(s) -
Hayashi Kenyu,
Hasegawa Yu,
Takemoto Yushin,
Cao Cheng,
Mukasa Akitake,
KimMitsuyama Shokei
Publication year - 2020
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14596
Subject(s) - intracerebral hemorrhage , medicine , oxidative stress , cerebral amyloid angiopathy , edema , anesthesia , disease , dementia , subarachnoid hemorrhage
Although Alzheimer's disease (AD) is associated with an increased risk of intracerebral hemorrhage (ICH) caused by hypertension and cerebral amyloid angiopathy, the precise clinical course after hypertensive ICH in AD patients is still unknown. In this study, we investigated how striatal ICH, a frequent site for hypertensive ICH, affected the prognosis of AD. We employed 17‐ and 18‐month‐old male 5XFAD (5X) mice and littermate (LT) controls, and striatal ICH was induced by collagenase injection. First, to address the acute effects of ICH on 5X mice, hemorrhagic volume and brain edema were evaluated 3 days after ICH. Next, to address the long‐term effects of ICH on 5X mice, morbidity, mortality, neurological function (beam‐walking and rotarod tests), and cognitive function (Y‐maze and nest‐building tests) were monitored. Twenty‐eight days later, the animals were euthanized, their brains were isolated, and the cytotoxic alterations were investigated. The results revealed that the acute effects of ICH were not significantly different between 5X and LT mice. In contrast, 5X mice showed significantly higher morbidity and mortality in response to ICH, as well as delayed neurological function recovery, compared to LT mice through 28 days. ICH did not affect cognitive function in either group. Infiltrated macrophages in the perihemorrhagic cortex, gp91 phox , p67 phox , and COX‐2 were significantly increased in 5X mice in response to ICH. We demonstrated that striatal ICH deteriorated prognosis and delayed neurofunctional recovery in 5X mice, which might be associated with enhanced oxidative stress in the presence of AD‐like pathology.