Sickle cell disease mice have cerebral oxidative stress and vascular and white matter abnormalities.

Sickle cell disease mice have cerebral oxidative stress and vascular and white matter abnormalities. Blood Cells Mol Dis. 2020 Sep 04;86:102493 Authors: Khaibullina A, Almeida LEF, Kamimura S, Zerfas PM, Smith ML, Vogel S, Wakim P, Vasconcelos OM, Quezado MM, Horkayne-Szakaly I, Quezado ZMN Abstract Strokes are feared complications of sickle cell disease (SCD) and yield significant neurologic and neurocognitive deficits. However, even without detectable strokes, SCD patients have significant neurocognitive deficits in domains of learning and memory, processing speed and executive function. In these cases, mechanisms unrelated to major cerebrovascular abnormalities likely underlie these deficits. While oxidative stress and stress-related signaling pathways play a role in SCD pathophysiology, their role in cerebral injury remains unknown. We have shown that Townes and BERK SCD mice, while not having strokes, recapitulate neurocognitive deficits reported in humans. We hypothesized that cognitive deficits in SCD mice are associated with cerebral oxidative stress. We showed that SCD mice have increased levels of reactive oxygen species, protein carbonylation, and lipid peroxidation in hippocampus and cortex, thus suggesting increased cerebral oxidative stress. Further, cerebral oxidative stress was associated with caspase-3 activity alterations and vascular endothelial abnormalities, white matter changes, and disruption of the blood brain...
Source: Blood Cells, Molecules and Diseases - Category: Hematology Authors: Tags: Blood Cells Mol Dis Source Type: research