[abstract] BRAIN METABOLIC, IONIC AND ELECTRICAL RESPONSES TO CARBON MONOXIDE (CO) INTOXICATION

Abstract

Carbon monoxide (CO) is a leading cause of poisoning deaths yet little is known about the neural and vascular mechanisms responsible for its intoxication processes as well as pathogenesis and mechanism of recovery (Thom and Keim, Clinical Toxicology 27: 141-156, 1989). One of the main reasons for this lack of information is the slow development of new technological tools for studying brain functions in vivo. Since CO intoxication occurs in awake humans, we adopted the awake animal model developed in our laboratory and applied it to CO intoxication studies (Mayevsky et al., J. Basic & Clin. Physiol. & Pharmacol. 1: 207-220, 1990). The multiprobe assembly (MPA) used in the present study, contained various probes by which the hemodynamic (CBF), metabolic (NADH redox state), ionic (K+, Ca2+, H+) and electrical activities of the awake brain were recorded in real-time mode. Male rats (180-220 gr) were anesthetized, operated on and the MPA was implanted (using dental acrylic) above the parietal cortex after removal of the dura matter. Three hours later the awake animal was exposed to 1000 ppm CO (40 min) followed by 3000 ppm CO (20 min) and then was allowed to rocover. Also, each rat was exposed to cortical spreading depression (brain activation) before, during as well as after the CO intoxication (KCl epidural application). The results obtained (12 rats) could be summarized as follows: 1. Exposure to 1000 ppm CO led to gradual and significant increase of CBF without any changes in NADH redox state or ion levels. 2. Under 3000 ppm the 02 delivery became a limiting factor as indicated by the increase in NADH redox state although the CBF was still very high. 3. In most rats, a wave of depolarization developed under 3000 ppm CO and the changes in the extracellular ion levels were similar to those recorded under spreading depression. The metabolic responses to the depolarization were typical to an ischemic brain. 4. Under 3000 ppm CO most rats had developed organized oscillations in CBF and NADH redox state suggesting that disturbances in CBF autoregulation did occur (Mayevsky and Ziv, Neurological Res. 13: 39-47, 1991). 5. The responses to spreading depression under CO intoxication suggested that the CBF compensation for the extra 02 needed in the activated brain was suboptimal.