Role of ATP-sensitive potassium channels and inflammatory response of basilar artery smooth muscle cells in subarachnoid hemorrhage of rabbit and immune-modulation by shikonin.

OBJECTIVE: To investigate the role of inflammatory response, oxidative damage and changes of ATP-sensitive potassium channels (sKATP) in basilar artery (BA) smooth muscle cells (SMCS) of rabbits in subarachnoid hemorrhage (SAH) model. METHODS: 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 KATP currents. The morphologies of basal arteries were analyzed. Protective effect of shikonin were also determine by same parameters. RESULTS: 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, KATP currents and morphological changes in basilar arteries. Shikokin pretreatment attenuated early inflammatory response at 24h and associated oxidative damage at 72h. Finally, shikonin attenuated morphological changes in basilar arteries and dysfunction. CONCLUSION: 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.

Hyperbaric Oxygen Intervention Modulates Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats: Possible Involvement of TLR4/NF-x03BA; B-Mediated Signaling Pathway.

BACKGROUND/AIMS: Previous studies have proved that the activation of TLR4/NF-x03BA; B signaling pathway is involved in inflammatory processes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Hyperbaric oxygen (HBO) intervention has successfully been used to treat several animal models of tissue injury via its anti-inflammation property. This study was undertaken to investigate the influence of HBO administration on the TLR4/NF-x03BA; B signaling pathway in rats at the early stage of SAH. METHODS: Male Sprague-Dawley rats (n = 150) were randomly divided into 5 groups: the sham, the sham + 2.8 atmospheres absolute (ATA) HBO group, the SAH group, the SAH + 2.0ATA HBO group, the SAH + 2.8ATA HBO group. Each group (n = 30) was randomly subdivided into three subgroups that were examined at the following time points: 24 h, 48 h and 72 h post-injury. HBO (100% O2, 2.0ATA or 2.8ATA for 90mins) was initiated 12 h after injury. Neurological deficit, brain edema and blood-brain barrier (BBB) permeability were assessed to evaluate the development of EBI. The expressions of TLR4, NF-x03BA; B and pro-inflammatory cytokines in the cortical were determined by real time polymerase chain reaction (RT-PCR), western blot, immunohistochemistry, or enzyme-linked immunosorbent assay (ELISA). RESULTS: Our study showed that treatment with HBO significantly decreased the expressions of TLR4, NF-x03BA; B and the downstream inflammatory agents, such as TNF-α, IL-6, IL-1ß and ICAM-1, and also improved brain edema, blood-brain barrier permeability and neurologic function. CONCLUSIONS: These findings indicate that HBO treatment may result in abatement of the development of EBI after SAH, possibly through suppression of TLR4/NF-x03BA; B signaling pathway.

Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage.

BACKGROUND: Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model. METHODS: Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1ß, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity. RESULTS: Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration. CONCLUSIONS: These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.