C1q/Tumor Necrosis Factor-Related Protein-3 Attenuates Brain Injury after Intracerebral Hemorrhage via AMPK-Dependent Pathway in Rat.
C1q/tumor necrosis factor (TNF)-related protein-3 (CTRP3) is a recently discovered adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP3 in intracerebral hemorrhage (ICH) is still mostly unresolved. The aim of the present report was to explore the possible neuroprotective effect of CTRP3 in an ICH rat model and to elucidate the fundamental mechanisms. ICH was induced in rats by intracerebral infusion of autologous arterial blood. The effects of exogenous CTRP3 (recombinant or lentivirus CTRP3) on brain injury were explored on day 7. Treatment with CTRP3 reduced brain edema, protected against disruption of the blood-brain barrier (BBB), improved neurological functions and promoted angiogenesis. Furthermore, CTRP3 greatly intensified phosphorylation of AMP-activated protein kinase (AMPK) in addition to expression of hypoxia inducing factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF). Finally, the protective effects of CTRP3 could be blocked by either AMPK or VEGF inhibitors. Our findings give the first evidence that CTRP3 is a new proangiogenic and neuroprotective adipokine, which may exert its protective effects at least partly through an AMPK/HIF-1α/ VEGF-dependent pathway, and suggest that CTRP3 may provide a new therapeutic strategy for ICH.
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Shaohua
S
Wang
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Yang
Y
Zhou
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Bo
B
Yang
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Lingyu
L
Li
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Shanshan
S
Yu
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Yanlin
Y
Chen
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Jin
J
Zhu
Department of Pathology, Chongqing Medical UniversityChongqing, China; Key Laboratory of Neurobiology, Chongqing Medical UniversityChongqing, China.
Yong
Y
Zhao
CTRP3; angiogenesis; blood-brain barrier disruption; brain edema; intracerebral hemorrhage; neuroprotection