Abstract 872: Inhibition of Spinal Astrocytes Activation Attenuates Myocardial Ischemia-Reperfusion Injury by Regulating NGF/TRPV1 Nociceptive Signaling

Abstract

Background and Aim: Spinal astrocytes activation are implicated in nociception and pain processing after noxious stimuli, while its role in cardiac ischemic nociception is unknown. We recently reported spinal nerve growth factor (NGF)-sensitized transient receptor potential vanilloid 1 (TRPV1) nociceptive signaling following cardiac ischemia and reperfusion (I/R). This study was design to investigate whether spinal astrocytes are activated following myocardial I/R and its effects on spinal NGF-TRPV1 signaling. Methods and Results: Myocardial I/R injury was induced by 30 min occlusion of the left coronary artery followed by 120 min of reperfusion in rats. Glial fibrillary acidic protein (GFAP), an astrocyte marker, was found up-regulated in thoracic spinal cord during ischemia and reperfusion. Intrathecally pre-injection of fluorocitrate (FC), an astrocyte inhibitor, reduced infarct size (IS/AAR, area at risk), from 48.4±2.67 to 29.7±3.13 (P<0.05, Fig.1 A). The high level of cardiac troponin T caused by I/R was decreased by FC injection as well (from 530±65 to 129±50 μg/μl, P<0.01, Fig.1 B). Upon immunofluorescence staining, GFAP immunopositive cells in spinal cord were found markedly increased after I/R, while the staining was suppressed by intrathecal FC administration (Fig.1 C). Moreover, the up-regualtion of NGF and TRPV1 protein levels in spinal cord were both inhibited by FC pretreatment (Fig.1 D-F). Conclusion: Myocardial I/R induced the activation of spinal astrocytes, inhibition of which reduces infarct size and cTnT level, as well as NGF-TRPV1 signaling, which suggests a novel therapeutic target for preventing myocardial ischemic injury.