MYOCARDIAL INFARCTION INDUCED NEUROLOGICAL IMPAIRMENT: IDENTIFYING DIFFERENTIAL RESPONSES FOLLOWING CARDIOVASCULAR INSULT

Myocardial infarction, or heart attack, is a highly prevalent form of heart disease which greatly contributes to morbidity worldwide. In addition to systemic complications, survivors of myocardial infarction (MI), often develop neurological dysfunction such as new onset anxiety and depression or cognitive impairment. However, the mechanisms behind these neurological impairments are poorly understood. To investigate the contribution of cerebrovasculature dysfunction to neurological impairment, we used a surgical model of MI in CD-1 wildtype mice. Specifically, after undergoing either the ligation of the left anterior descending coronary artery or a sham surgical procedure, mice underwent behavioural testing and tissue collection at 3-, 7- and 14-days post-surgery. Results of behavioural testing demonstrated anxiety-like behaviour and motor impairments at 3- and 7-days alongside cognitive impairments at 14-days post-surgery in the MI animals when compared to sham animals. To understand the relationship between behavioural and cerebrovascular changes, we performed western blot analysis to evaluate markers of the blood-brain barrier and found that animals with more acute changes to the blood-brain barrier also displayed more severe behavioural impairments, indicating a potential biological divergence in neuronal response following cardiovascular insult. Finally, blood vessel analysis indicated differences between conditions, with MI animals demonstrating lower vessel density and a reduced quantity of small vessels. Taken together, these findings illuminate potential mechanisms that may contribute to the development of neurological sequelae following MI, representing a critical step toward the development of more comprehensive therapeutic strategies.