Brainstem and hypothalamic areas activated by tissue hypoxia: Fos-like immunoreactivity induced by carbon monoxide inhalation in the rat.

Acute ambient hypoxia interacts with the ventilatory and cardiocirculatory control systems, via the concomitant activation of arterial chemoreceptors and tissue oxygen-sensing mechanisms. Whether these latter mechanisms may trigger a specific pathway had not yet been elucidated. We addressed this issue, mapping Fos expression in adult conscious rats subjected to tissue hypoxia elicited by carbon monoxide inhalation, under conditions of minimal activation of arterial chemoreceptors. Brief stimuli have been delivered (1% carbon monoxide inhaled during 5, 10 or 20 min) to produce steady tissue hypoxia. Compared to normoxia, even the briefest stimuli led to marked neuronal activation within areas involved in ventilatory and cardiocirculatory control. In the brainstem, stimulated rats exhibited enhanced Fos expression in the nucleus of the solitary tract, the area postrema, the dorsal motor nucleus of the vagus nerve, the ventrolateral medulla, the parapyramidal group, the nucleus raphe pallidus, the lateral paragigantocellular nucleus, the locus coeruleus, the dorsal raphe nucleus, the lateral parabrachial area, and the ventrolateral central gray. In the hypothalamus, activated neurons were identified at the ventral border and in the supramamillary, posterior, and dorsomedial nuclei. Fos expression appeared with increasing the severity of tissue hypoxia in the retrotrapezoid nucleus, the ventral tegmental area and the arcuate and paraventricular hypothalamic nuclei. The present data support the idea that inputs related to tissue hypoxia might play a crucial role in patterning the physiological response to hypoxia.