Evidence for neuroinflammation after myocardial infarction in a mouse model

Abstract

Background: The cardiovascular system and central nervous system are known to influence each other. Accordingly, neurological changes may occur after myocardial infarction (MI), which may be mediated by neuroinflammation. We investigated tumor necrosis factor alpha (TNF-α) and microglia activation in post-MI neuroinflammation. Materials and Methods: MI or sham surgery was induced in 28 male mice. Two weeks later, we performed echocardiography and dissected the brains for the western blot on TNF-α and its receptors (n = 10) or immunohistochemical stainings for microglia, doublecortin X (DCX), and TNF-α (n = 18). Plasma was collected for the measurement of circulatory cytokines. Results: The MI mice had an average infarct size of 38% of the left ventricle, heart failure was confirmed by decreased fractional shortening and increased lung weight. Plasma cytokine levels were unaltered. In brains of MI mice, there was a higher expression of TNF-α precursor protein, with trends for higher TNF-R1 and lower TNF-R2 expression. Furthermore, MI mice had more activated microglia in the inner blade of the dentate gyrus of the hippocampus. The amount of neurogenesis measured by DCX staining was unaltered. Conclusions: Our mouse model of MI showed signs of persistent neuroinflammation as indicated by raised levels of TNF-α precursor protein and an increased number of activated microglia in the hippocampus. The extent to which these neuroinflammatory hallmarks influence central nervous system functioning remain to be determined.

Keywords

• microglia
• myocardial infarction
• neurogenesis
• neuroinflammation
• tumor necrosis factor alpha