The correlation between accumulation of amyloid beta with enhanced neuroinflammation and cognitive impairment after intraventricular hemorrhage

OBJECTIVE Intraventricular hemorrhage (IVH) is found in approximately 40% of intracerebral hemorrhages and is associated with increased mortality and poor functional outcome. Cognitive impairment is one of the complications and occurs due to various pathological changes. Amyloid beta (A beta) accumulation and neuroinflammation, and the Alzheimer disease-like pathology, may contribute to cognitive impairment. Iron, the degradation product of hemoglobin, correlates with A beta. In this study, the authors investigated the correlation between A beta accumulation with enhanced neuroinflammation and cognitive impairment in a rat model of IVH. METHODS Nine male Sprague-Dawley rats underwent an intraventricular injection of autologous blood. Another 9 rats served as controls. Cognitive function was assessed by the Morris water maze and T-maze rewarded alternation tests. Biomarkers of A beta accumulation, neuroinflammation, and c-Jun N-terminal kinase (JNK) activation were examined. RESULTS Cognitive function was impaired in the autologous blood injection group compared with the control group. In the blood injection group, A beta accumulation was observed, with a co-located correlation between iron storage protein ferritin and A beta. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) activity was elevated. Microgliosis and astrogliosis were observed in hippocampal CA1, CA2, CA3, and dentate gyrus areas, with elevated proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1. Protein levels of phosphorylated JNK were increased after blood injection. CONCLUSIONS A beta accumulation and enhanced neuroinflammation have a role in cognitive impairment after IVH. A potential therapeutic method requires further investigation.