VENTILATORY EFFECTS OF GLIAL DYSFUNCTION IN A RAT-BRAIN STEM CHEMORECEPTOR REGION

Glia are thought to be important in brain extracellular fluid ion and pH regulation, but their role in brain stem sites that sense pH and st imulate breathing is unknown. Using a diffusion pipette, we administer ed the glial toxin, fluorocitrate (FC; 1 mM) into one such brain stem region, the retrotrapezoid nucleus (RTN) for 45-60 min. This dose and time period were chosen so that the effects of FC would be largely rev ersible. Within minutes, tissue pH decreased, and respiratory output i ncreased. Both recovered almost completely after cessation of FC admin istration. The response to systemic CO2 stimulation was unaffected by FC treatment compared with that following control diffusion. Anatomic analysis showed, at the center of FC administration, some small (mean diameter = 5.1 mu m) cells that stained for DEAD Red, a marker for alt ered cell membrane permeability, and some fragmented glia (glial fibri llary acidic protein immunohistochemistry). The average RTN tissue vol ume that contained such DEAD Red-positive cells was 271 nl, similar to 23% of the volume of one RTN region. Reversible disruption of glia in the RTN, a region known to contain central chemoreception, results in an acidic local pH and in stimulation of respiratory output.