naphthoquinones and Subarachnoid-Hemorrhage

To investigate the role of inflammatory response, oxidative damage and changes of ATP-sensitive potassium channels (sK. Time course studies on inflammatory response by real-time PCR, oxidative process and function of isolated basilar artery after SAH in New Zealand White rabbits were performed. Basilar artery smooth muscle cells (BASMCs) in each group were obtained and whole-cell patch-clamp technique was applied to record cell membrane capacitance and K. Inflammatory cytokines levels were highest at 24h compare to 72h after SAH whereas the oxidative damage and cell death marker were at highest peak at 72h. Oxidative damage peak coincided with significant alterations in cell membrane capacitance, K. Currents of ATP-sensitive potassium channels in basilar smooth muscle cells decreased after SAH by putative oxidative modification from immediate inflammatory response and can be protected by shikonin pretreatment.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Basilar Artery; Cytokines; Female; Inflammation Mediators; KATP Channels; Male; Muscle, Smooth, Vascular; Naphthoquinones; Oxidative Stress; Patch-Clamp Techniques; Rabbits; Subarachnoid Hemorrhage

High-mobility group box 1 (HMGB1) was shown to be a major extracellular mediator involved in relayed neuro-inflammation in animals after subarachnoid hemorrhage (SAH). It is of interest to examine the effect of rhinacanthin-C (RCT-C, C25H30O5) on pro-inflammatory cytokines/HMGB1 in an SAH-related early brain injury model.. A rodent double SAH model was used. RCT-C was administered orally at 100, 200, and 400 μmol/kg/day. Cerebral spinal fluid samples were obtained to assess interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α using a real-time polymerase chain reaction. Basilar arteries were harvested and cerebral cortex was examined for HMGB1 mRNA and protein expression (western blot) and caspases (real-time polymerase chain reaction). An intrathecal injection of 1 ng of HMGB-1 recombinant protein was given in the 400 μmol/kg/day RCT-C plus SAH groups.. The levels of IL-1β, IL-6, and tumor necrosis factor α mRNA were significantly increased in animals subject to SAH, compared with the healthy controls, but were absent in the RCT-C groups. Cleaved caspase-9a as well as HMGB-1 mRNA and protein were significantly reduced in the 400 μmol/kg/day RCT-C treatment groups. Similarly, administration of RCT-C reduced HMGB-1 mRNA and protein expression (P <0.01).. RCT-C exerts a neuroprotective effect by reducing cleaved caspase-3- and caspase-9a-related apoptosis. Decreased HMGB-1 mRNA and protein expression in the RCT-C groups corresponds to its anti-inflammatory effect. HMGB-1 recombinant protein administration impaired the neuroprotective and immunosuppressive effect of RCT-C. This finding lends credence that RCT-C modulates the HMGB-1-related pathway and attenuates brain apoptosis in the pathogenesis of SAH.

Topics: Acanthaceae; Animals; Apoptosis; Basilar Artery; Brain; Cerebral Cortex; Cytokines; Dose-Response Relationship, Drug; Hemodynamics; HMGB1 Protein; Injections, Intraventricular; Male; Naphthoquinones; Neuritis; Neuroprotective Agents; Plant Extracts; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Subarachnoid Hemorrhage