Table 2.
The Potential Role of Microglia in Myocardial Infarction and Cardiac I/R Injury
| Model of MI or I/R | Treatment Details | Major Findings | Conclusion | References | |
|---|---|---|---|---|---|
| Animals | Protocol | ||||
| Male Sprague–Dawley rats | Ligation of the left anterior descending coronary artery | Infusion of minocycline (172 ng/mL, 0.3 μL/h) | 1. After 12 weeks, MI contributed to dramatically increased numbers of activated microglia. 2. Minocycline treatment decreased the number of Iba-1+ and FRA+ cells in the PVN and the percentage of activated microglia in the PAG and RVLM. 3. No evidence of improved heart function with minocycline. |
Inflammation occurs in brain nuclei, and inhibition of microglia activation may not be sufficient to ameliorate cardiac dysfunction. | [76] |
| Male Sprague–Dawley rats (200–250 g) | Coronary artery ligation | Intraperitoneal (i.p.) administration of the P2X7R antagonist Brilliant Blue-G (BBG, 25 or 50 mg/kg injection per day for 5 days) before surgery | 1. Colocalization of P2X7R with Iba-1 in the PVN rather than neurons was observed after MI surgery. 2. BBG application reduced the expression of P2X7R, IL-1β and TNF-α in the PVN, and improved cardiac function by decreasing MAP, HR, IVP and LVEDP, and the LF/HF ratio. |
Inhibition of P2X7R activation in the PVN may be an effective method for the current treatment of AMI. | [81] |
| Male Sprague‒Dawley rats (50–60 days, approximately 280 g) | Coronary artery ligation | PVN microinjection of Mincle siRNA 24 hours prior to MI surgery (250 pmol/50 nL) | 1. The upregulation of Mincle receptor, NLRP3/IL-1β pathway were observed post-MI, and IF suggested that the Mincle receptor colocalized with microglia within the PVN. 2. Mincle knockdown decreased the number of Iba-1+ cells, inhibited the NLRP3/IL-1β pathway in the PVN and reduced RSNA and NE concentrations. |
Inhibition of Mincle ameliorates sympathetic hyperactivity meditated by the NLRP3/IL‐1β pathway. | [83] |
| Male Sprague–Dawley rats (50–60 days, approximately 260 g) | Coronary artery ligation of LAD | Silence the TLR4 gene in microglia of the PVN via a shRNA | 1. After MI, TLR4 was activated predominantly in microglia in the PVN, and NF-κB signaling and ROS production were upregulated. 2. TLR4 gene silencing contributed to the decreased levels of NE and RSNA, and induced the downregulation of NF-κB, IL-1β, and TNF-α expression. |
Inhibition of TLR4 attenuated sympathoexcitation. | [84] |
| Sprague–Dawley rats (250–300 g) | Ligation of the LAD for 30 min and reperfusion for 3 h | LED light source (610 nm) illumination | LED illumination significantly inhibited LSG neural activity and decreased microglia activation and the levels of IL-1β, TNF-α and NGF | LED therapy reduced microglia activation and pro-inflammatory cytokine expression after cardiac I/R | [90] |
Abbreviations: MI, myocardial infarction; FRA, fos-related antigens; IVP, intraventricular pressure; LVEDP, left ventricular end-diastolic pressure; NLRP3, NOD-like receptor protein 3; RSNA, renal sympathetic nerve activity; TLR4, Toll-like receptor 4; NF-κB, nuclear factor kappa-B; LAD, left anterior descending; I/R, ischemia/reperfusion; LED, light emitting diode; NGF, nerve growth factor.