Myocardial Infarction Induces Neuroinflammatory Processes and Triggers Oligodendrocytes Proliferation and Maturation

Background. Cardiovascular diseases are considered the first leading cause of death worldwide, with myocardial infarction (MI) being the most prevalent disorder among them. Research studies showed a strong correlation between MI and cerebrovascular diseases. For example, after MI, patients are highly susceptible to develop various cognitive and behavioral disorders, such as Alzheimer’s disease and dementia. Literature data indicate that MI triggers both local and systemic inflammatory responses; however, it remains unclear whether MI might also cause neuroinflammatory processes activation. This study, by using a myocardial infarction mouse model, aims to investigate the potential effects of MI on the activation of neuroinflammatory processes and on the homeostasis of brain oligodendrocyte cells. Methods. Mice were subjected to permanent ligation of the left anterior descending coronary artery (MI-group). Sham-operated mice were used as control. Mice were sacrificed at day 1, 2, 14 and 28 post-surgery. Brains were dissected and processed for gene and protein expression and immunohistochemical analyses. Results. Following MI, activation of neuroinflammatory processes was observed. Gene expression analysis showed an increased expression level of Tnf-α and Ccl-2 in the brain cortex. Additionally, the microglial NLRP3 inflammatory signaling pathway was upregulated, as appeared by the significant increase in expression of Cxcl-2, Caspase-1 and IL-1β genes. Furthermore, immunohistochemical analysis demonstrated a significant increase in the number of microglial and infiltrated macrophage cells (Iba-1 positive cells) in the brain cortex and corpus callosum. Oligodendrocyte cells homeostasis, in terms of proliferation and maturation, was affected following MI and appeared as a significant increase in the number of BrdU- and GSTπ- oligodendrocyte positive cells. Conclusion. The results indicate that MI induces continuous activation of neuroinflammatory processes, suggesting the potential development of cerebrovascular disorders in the long term, and triggers oligodendrocytes proliferation and maturation as a potential protective response.