Effect of Intrahippocampal Administration of α7 Subtype Nicotinic Receptor Agonist PNU-282987 and Its Solvent Dimethyl Sulfoxide on the Efficiency of Hypoxic Preconditioning in Rats

We have previously suggested a key role of the hippocampus in the preconditioning action of moderate hypobaric hypoxia (HBH). The preconditioning efficiency of HBH is associated with acoustic startle prepulse inhibition (PPI). In rats with PPI > 40%, HBH activates the cholinergic projections of hippocampus, and PNU-282987, a selective agonist of α7 nicotinic receptors (α7nAChRs), reduces the HBH efficiency and potentiating effect on HBH of its solvent dimethyl sulfoxide (DMSO, anticholinesterase agent) when administered intraperitoneally. In order to validate the hippocampus as a key structure in the mechanism of hypoxic preconditioning and research a significance of α7nAChR activation in the hypoxic preconditioning, we performed an in vivo pharmacological study of intrahippocampal injections of PNU-282987 into the CA1 area on HBH efficiency in rats with PPI ≥ 40%. We found that PNU-282987 (30 μM) reduced HBH efficiency as with intraperitoneal administration, while DMSO (0.05%) still potentiated this effect. Thus, direct evidence of the key role of the hippocampus in the preconditioning effect of HBH and some details of this mechanism were obtained in rats with PPI ≥ 40%. The activation of α7nAChRs is not involved in the cholinergic signaling initiated by HBH or DMSO via any route of administration. Possible ways of the potentiating action of DMSO on HBH efficiency and its dependence on α7nAChRs are discussed.

Combined preconditioning with tetra-(1-vinylimidazole) cobalt dichloride

The aim of this study was to investigate the vinylimidazole derivative as pharmacological preconditioning in experimental acute hypoxia and cerebral ischemia. All experiments were conducted with mice and rats. Acute hypoxia with hypercapnia was modeled by placing the mice in a glass with a glass lid shtanglazy 250 ml. Acute hypobaric hypoxia was performed putting animals under a glass cope, where from the Kamovsky pump pumped up the air which is equal to the altitude of 5000 meters (moderate hypoxia) and 11 000 meters (severe hypoxia). Cerebral ischemia in rats was modeled by one-stage bilateral common carotid artery occlusion. Separate pharmacological and hypoxic preconditioning and combined preconditioning by alternately use of pharmacological and hypoxic factors were investigated. It was revealed that combined preconditioning (tetra-(1-vinylimidazole) cobalt dichloride 30 mg/kg + moderate hypobaric hypoxia) enhance the resistance of the animal organism to acute hypoxia in the early period (in 1 hr) and delayed period (in 48 hr) more effective than the separate preconditioning by moderate hypoxia or with the help of tetra-(1-vinylimidazole) cobalt dichloride. The combined preconditioning increase the survival of rats in the early periods and in the delayed periods of cerebral ischemia performance, but doesn’t reduce the severity of neurological deficit in the surviving animals registered with the Stroke Index McGraw scale.