CTRP9 ATTENUATES NEUROVASCULAR INJURY IN ACUTE ISCHEMIC STROKE

Background: C1q/TNF-related protein 9 (CTRP9) is a recently recognized adipokine (singular) primarily expressed in adipose tissue, contributing to metabolic regulation and protection against vascular diseases. We examined whether CTRP9 confers neuroprotection after acute cerebral ischemia-reperfusion injury.
Methods: Experimental stroke was induced in 8-week-old male C57BL/6 mice using transient middle cerebral artery occlusion (tMCAO). After 1 hour of occlusion followed by reperfusion, mice were immediately administered either CTRP9 (0.5 mg/kg) or saline. Neurological deficits were evaluated at 1 and 24 hours after surgery. Brain tissues were collected after reperfusion for the assessment of infarct volume, blood-brain barrier (BBB) permeability, and molecular analyses. Tissue damage and BBB integrity were evaluated using histological stain. Inflammatory responses and apoptosis signaling were analyzed via Western blot, quantitative real-time PCR, and immunofluorescence.
Results: CTRP9 administration exerted acute neuroprotective effects 24 hours after ischemia, as demonstrated by a significant reduction in infarct volume and improved neurological recovery (p < 0.01). Blood–brain barrier disruption was significantly attenuated (p < 0.05), accompanied by increased endothelial nitric oxide synthase (eNOS) expression (p < 0.05). Although no significant changes were observed in inflammatory cytokine levels, CTRP9 markedly reduced endoplasmic reticulum (ER) stress (p < 0.01) and apoptosis (p < 0.005) in pericytes, while promoting neurogenesis in the ischemic brain.
Conclusions: Our findings demonstrate that CTRP9 exerts potent neuroprotective effects in acute cerebral I/R injury by preserving BBB integrity and reducing ER stress in pericytes. These results suggest that CTRP9 is a promising therapeutic target for ischemic stroke.