Variety of Neuronal Pathways to Achieve the Same Hypoxic Preconditioning Effect

The relevance of hypoxic preconditioning is due to its ability to increase the body's resistance to hypoxic/ischemic stress. A single session of moderate hypoxia eliminates the differences in endurance under severe hypoxia in intact rats and those pre-tested under severe hypoxia with high and low innate resistance to it. In these rat groups, the same preconditioning effect is achieved by different synaptic plastic tools (biochemical data). Thus, the synaptic mechanisms of preconditioning are dependent on the prior hypoxic experience. This conclusion confirmed our pharmacological experiments. Antagonists of alpha7 and non-alpha7 subtypes of the nicotinic receptors methyllycaconitine and mecamylamine in single IP injections selectively influenced the resistance to hypoxia of the low-resistant rats and were ineffective against the high-resistant and intact rats. Moreover, in the low-resistant rats, both drugs had ambiguous effects on the resistance to hypoxia after the preconditioning and without it. Based on the data, we substantiated in our review that the following cholinergic neuronal populations and networks were involved in mechanisms of the hypoxic preconditioning: 1) In the high-resistant rats, cholinergic projections from the pedunculopontine and/or laterodorsal tegmental nuclei into the nuclei of the ventrolateral medulla of the medulla oblongata as well as into the subcortical forebrain nuclei and, linked with them, cholinergic projections from these forebrain nuclei into the cortex. 2) In the low-resistant rats, cholinergic C-fibres into the nucleus tractus solitary of the medulla oblongata and influences of unidentified cholinergic neurons through the alpha7 nicotinic receptors in the caudal brainstem areas outside the nucleus tractus solitary. 3) In intact rats, cortical cholinergic interneurons and unidentified cholinergic neurons of the brainstem structures. In conclusion, the variety of neuronal pathways to put off apnea indicates a great adaptive potential of brain, and the specific mechanisms of its realization may be a promising therapeutic targets.