C1q/tumor necrosis factor-related protein 3 inhibits oxidative stress during intracerebral hemorrhage via PKA signaling.

C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) have been confirmed to be adiponectin (APN) paralogs and some share APN's metabolic regulatory functions. Oxidative stress contributes to brain injury after intracerebral hemorrhage (ICH) and APN can inhibit oxidative stress injury during ICH. Thus, we addressed the role of a specific CTRP-CTRP 3-after experimental ICH and studied post-ICH oxidative stress injury and the pathway involved. ICH was induced in rats via intracerebral infusion of autologous blood, and the effects of exogenous CTRP3 (lentivirus or recombinant CTRP3) replenishment on ICH injury were investigated. Rats received an intracerebral injection of H89 (a PKA inhibitor) with recombinant CTRP3 (rCTRP 3) or dibutyryl cyclic AMP (db-cAMP, a PKA activator) without rCTRP 3. Then, oxidative stress, CTRP 3, PKA, and NADPH oxidase-2 (NOX 2) were assessed, as were functional outcomes, cerebral edema, and blood-brain barrier (BBB) permeability at 24h. We found that treatment with recombinant or lentivirus CTRP3 reduced cerebral edema and BBB damage and improved neurological functions as well as reduced post-ICH elevated reactive oxygen species and malondialdehyde and increased reduced glutathione and the ratio of oxidized to reduced glutathione. CTRP 3 applied 30min after ICH increased PKA, reduced NOX 2 expression, and decreased oxidative stress. A PKA-inhibitor abolished CTRP 3-induced protective effects and increased NOX 2 expression. We conclude from our results that CTRP 3 may regulate oxidative stress injury via PKA signaling and may provide a new therapeutic strategy for ICH.