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Microglia are the immune cells in the central nervous system and can produce cytokines when they are activated by an insult or injury. In the present study, we investigated in detail the time frame of the activation of microglia in the hypothalamic paraventricular nucleus (PVN) following myocardial infarction in rats. Morphological changes and immunohistochemistry to detect CD11b (clone OX-42) were used to identify activated microglia. Compared to rats that had undergone sham surgical procedures, there was a significant increase of between 40 and 50% in the proportion of activated microglia in the PVN 4-16 weeks following myocardial infarction (P<0.001, One way ANOVA). At 24h or 1 week post myocardial infarction, however, there was no significant increase in the proportion of activated microglia. Echocardiography and haemodynamic parameters after myocardial infarction indicated significantly reduced left ventricular function. In conclusion, following myocardial infarction, activation of microglia in the PVN does not occur immediately but once manifested, activation is sustained. Thus, activated microglia may contribute to the chronic elevation in cytokine levels observed following myocardial infarction. Since cytokines elicit sympatho-excitatory effects when locally microinjected into the PVN, activated microglia may contribute to the mechanisms mediating the chronic increase in sympathetic nerve activity in animals with reduced left ventricular function induced following myocardial infarction.
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