Oxidized low-density lipoprotein receptor 1: a novel potential therapeutic target for intracerebral hemorrhage

Abstract

Oxidized low-density lipoprotein receptor 1 (OLR1) is upregulated in neurons and participates in hypertension-induced neuronal apoptosis. OLR1 deletion exerts protective effects on cerebral damage induced by hypertensive-induced stroke. Therefore, OLR1 is likely involved in the progress of intracerebral hemorrhage. In this study, we examined the potential role of OLR1 in intracerebral hemorrhage using a rat model. OLR1 small interfering RNA (10 μL; 50 pmol/μL) was injected into the right basal ganglia to knock down OLR1. Twenty-four hours later, 0.5 U collagenase type VII was injected to induce intracerebral hemorrhage. We found that knockdown of OLR1 attenuated neurological behavior impairment in rats with intracerebral hemorrhage and reduced hematoma, neuron loss, inflammatory reaction, and oxidative stress in rat brain tissue. We also found that silencing of OLR1 suppressed ferroptosis induced by intracerebral hemorrhage and the p38 signaling pathway. Therefore, silencing OLR1 exhibits protective effects against secondary injury of intracerebral hemorrhage. These findings suggest that OLR1 may be a novel potential therapeutic target for intracerebral hemorrhage.

Keywords

• ferroptosis; inflammation; intracerebral hemorrhage; neurological behavior; neuroprotection; novel therapeutic target; oxidative stress; oxidized low-density lipoprotein receptor 1; p38 signaling pathway; secondary brain injury