Recombinant HMGB1 (R&D System, Minneapolis, MN) was dissolved in phosphate-buffered saline and administered ip 50 μg/kg, a dose that we had earlier reported to produce a similar inflammatory and cognitive response as that seen after surgery.5 (link)Dexmedetomidine (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in 0.9% sterile saline and administered 50 μg/kg ip every 2 hours for three doses immediately following HMGB1 (Figure 1 A, B ) or at 20 μg/kg ip for four doses in the surgical model (Figure 1 C, D ). These doses were selected to simulate perioperative sedation either with (Figure 1 C, D ) or without isoflurane anesthesia (Figure 1 A, B ).
Yohimbine (Sigma-Aldrich) was dissolved in 0.9% sterile saline and 1.5 mg/kg was administered ip, a dose that effectively blocks α2 adrenoceptor-mediated responses.17 (link)Atipamezole (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in 5% dimethyl sulfoxide in saline and 3 mg/kg was administered ip, a dose that effectively blocks both imidazole receptor and α2 adrenoceptor-mediated responses.
Methyllycaconitine (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in 0.9% sterile saline and 4mg/kg ip was administered, a dose that blocks α7 nicotinic acetylcholine receptor-mediated response.2 (link)
Yohimbine (Sigma-Aldrich) was dissolved in 0.9% sterile saline and 1.5 mg/kg was administered ip, a dose that effectively blocks α2 adrenoceptor-mediated responses.17 (link)Atipamezole (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in 5% dimethyl sulfoxide in saline and 3 mg/kg was administered ip, a dose that effectively blocks both imidazole receptor and α2 adrenoceptor-mediated responses.
Methyllycaconitine (Sigma-Aldrich, St. Louis, MO, USA) was dissolved in 0.9% sterile saline and 4mg/kg ip was administered, a dose that blocks α7 nicotinic acetylcholine receptor-mediated response.2 (link)
