Light Emitting Diode Therapy Protects against Myocardial Ischemia/Reperfusion Injury through Mitigating Neuroinflammation

Abstract

Background. Neuroinflammation plays a key role in myocardial ischemia-reperfusion (I/R) injury. Previous studies showed that light-emitting diode (LED) therapy might improve M2 microglia activation and brain-derived neurotrophic factor (BDNF) expression, thereby exerting anti-inflammatory effects. Therefore, we hypothesized that LED therapy might reduce myocardial I/R injury by neuroinflammation modulation. Objective. To explore the effect of LED therapy on myocardial I/R-induced injury and seek the underlying mechanism. Methods. Thirty rats were randomly divided into three groups: Control group (without LED treatment or myocardial I/R, n=6), I/R group (with myocardial I/R only, n=12), and LED+I/R group (with myocardial I/R and LED therapy, n=12). Electrocardiogram was recorded continuously during the procedure. In addition, brain tissue was extracted for BDNF, Iba1, and CD206 analyses, and heart tissue for myocardial injury (ischemic size and infarct size), IL-4 and IL-10 mRNA analysis. Results. In comparison with the I/R group, the ischemia size and the infarct size were significantly attenuated by LED therapy in the LED+I/R group. Meanwhile, the microglia activation induced by I/R injury was prominently attenuated by LED treatment either. And it is apparent that there was also an increase in the beneficial neuroinflammation markers (BDNF and CD206) in the paraventricular nucleus (PVN) in the LED+I/R group. Furthermore, the anti-inflammatory cytokines, IL-4 and IL-10, were greatly decreased by I/R while improved by LED treatment in myocardium. Conclusion. LED therapy might reduce neuroinflammation in PVN and decrease myocardium injury by elevating BDNF and M2 microglia.

Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases

“…Recently, our studies showed that LED therapy (2.0 J/cm 2 , 610 nm) located at the skull surface of the hypothalamic PVN through the scalp and skull from 30 min before ischemia to 3 h after reperfusion could significantly attenuate the ischemia and infarct size following cardiac I/R. 90 In addition, LED illumination significantly reduced the inducibility of ventricular arrhythmias after I/R injury. The attenuated activation of microglia and subsequently decreased peripheral sympathetic activity contribute to the protective effects of LED therapy against cardiac I/R injury.…”

“… 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. …”

Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats

“…Studies have shown that many cardiovascular diseases, such as MI, HF and hypertension, are characterized by reduced cardiac function due to peripheral inflammation associated with increased central sympathetic tone, while neuroinflammation of the PVN in turn leads to increased central sympathetic tone. 4 Under hypertensive conditions, the PVN activates and releases NE, 23 an excitatory neurotransmitter, thereby promoting sympathetic output. 24 , 25 In studying diseases such as memory impairment and neurological damage after cerebral ischaemia‐reperfusion, animal models of cerebral ischaemic stroke reflect that the TLR4/MyD88/NF‐kB axis is involved in neuroinflammation.…”

“…Neuroinflammation in the paraventricular nucleus (PVN) of the hypothalamus is a key factor in increased sympathetic activity, which is the basis for the pathogenesis of many cardiovascular diseases, including MI. 3 , 4 Numerous studies have shown that acute myocardial infarction (AMI) induces an early inflammatory response, resulting in a neuroinflammatory response and oxidative stress within the PVN, which leads to neuronal excitation within the PVN and the promotion of stellate ganglion (STG) remodelling and inflammatory infiltration, eventually leading to cardiac sympathetic excitation. 5 , 6 , 7 , 8 However, the exact mechanism of how PVN induces sympathetic excitation and ultimately leads to VAs in the heart is unclear.…”

Tackling Ischemic Reperfusion Injury With the Aid of Stem Cells and Tissue Engineering

“…These, then produce dynamic shear stress, hydrostatic pressure, mechanical modulation of SCs, and tailored diffusivity (Adamo and García-Cardeña, 2011;Estrada et al, 2011;Ali et al, 2020). In addition, biophysical cues, such as optic and magnetic/electric, could be provided to culture chambers to further influence SCs fate (Wang et al, 2020). This consequently minimize the use of expensive biochemical signals.…”