TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.

BACKGROUND: T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. METHODS: We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. RESULTS: TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. CONCLUSIONS: TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats.

Remifentanil requirements for preventing motor response to skin incision in healthy women anesthetized with combinations of propofol and dexmedetomidine titrated to similar Bispectral Index (BIS) values.

BACKGROUND: It is unclear whether the sedative, analgesic or sympatholytic effects of adjunctive dexmedetomidine contribute to reduced analgesic requirements in general anesthesia. This study aimed to assess the analgesic effect of dexmedetomidine on intraoperative opioid requirements using body movement as observation indicator at similar BIS-guided sedative depth in propofol anesthesia. METHODS: Ninety patients were randomly divided into three groups to receive administration of saline, and dexmedetomidine at 0.5 and 1.0 µg kg(-1) over 10 min, followed by saline and dexmedetomidine at infusion rates of 0.17 and 0.33 µg kg(-1) h(-1), respectively. After dexmedetomidine and saline bolus administration, propofol was titrated to maintain the BIS values at 45-55. When BIS values reached the predetermined range, remifentanil was administered by target-controlled infusion. Five minutes following remifentanil treatment, skin was incised and the motor response observed. Then, the concentration of remifentanil blunting the motor response in 50% of patients (Ce50) was determined using a modified Dixon's sequential 'up-and-down' method. RESULTS: Dexmedetomidine significantly decreased effect-site concentrations of propofol for maintaining the preset BIS range (P < 0.01). The Ce50 (95% CI) of remifentanil were 0.93 (0.82-1.03), 1.03 (0.89-1.17) and 0.91 (0.77-1.06) ng ml(-1) in the 0 (saline), 0.5 and 1.0 µg kg(-1) dexmedetomidine groups, respectively, indicating non-statistically significant differences among groups (P > 0.0167). CONCLUSIONS: Propofol and its combination with dexmedetomidine have similar opioid requirements for preventing motor response to skin incision when titrated to similar BIS values. These findings indicate that adjunctive dexmedetomidine for general anesthesia has sedative but no opioid sparing effects.