title: Attenuation of microglial and neuronal activation in the brain by ICV minocycline following myocardial infarction.
abstract: Following myocardial infarction, microglia, the immune cells in the central nervous system, become activated in the hypothalamic paraventricular nucleus (PVN) suggesting inflammation in this nucleus. Little is known about other brain nuclei. In the present study, we investigated whether the rostral ventrolateral medulla (RVLM), the nucleus tractus solitarius (NTS) and the periaqueductal grey (PAG), regions known to have important cardiovascular regulatory functions, also show increased microglial activation and whether this coincides with increased neuronal activity. We also investigated whether minocycline inhibited microglial activation and whether this also affected neuronal activity and cardiac function. Compared to controls there was a significant increase in the proportion of activated microglia and neuronal activation in the PVN, RVLM, NTS and PAG, 12weeks following myocardial infarction (P<0.001). Intracebroventricular infusion of minocycline (beginning one week prior to infarction) significantly attenuated the increase in microglial activation by at least 50% in the PVN, RVLM, PAG and NTS, and neuronal activation was significantly reduced by 50% in the PVN and virtually abolished in the PAG, RVLM and NTS. Cardiac function (percent fractional shortening) was significantly reduced by 55% following myocardial infarction but this was not ameliorated by minocycline treatment. The results suggest that following myocardial infarction, inflammation occurs in brain nuclei that play key roles in cardiovascular regulation and that attenuation of this inflammation may not be sufficient to ameliorate cardiac function.
authors.affiliation: School of Medical Sciences, and Health Innovations Research Institute, RMIT University, Melbourne, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dworak
authors.affiliation: School of Medical Sciences, and Health Innovations Research Institute, RMIT University, Melbourne, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Stebbing
authors.affiliation: Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Kompa
authors.affiliation: School of Medical Sciences, and Health Innovations Research Institute, RMIT University, Melbourne, Australia.
authors.forename: Indrajeetsinh
authors.initials: I
authors.lastname: Rana
authors.affiliation: Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: School of Medical Sciences, and Health Innovations Research Institute, RMIT University, Melbourne, Australia. Electronic address: emilio.badoer@rmit.edu.au.
authors.forename: Emilio
authors.initials: E
authors.lastname: Badoer
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010784:Photomicrography; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D008911:Minocycline
keywords: Dorsomedial medulla; Hypothalamus; Inflammation; Microglial and neuronal activation; Periqueductal grey; Ventrolateral medulla; left ventricular dysfunction