Cerebral Neuronal Transmission

Abstract

Low oxygen tension profoundly disturbs cerebral function. Studies in the 1930s demonstrated a rapid loss of EEG acitivity when animals breathed nitrogen. 2,14 The studies of Siesjo and many coworkers have described the steady-state effects of hypoxia on neural function and cerebral metabolites, particularly those involved in energy metabolism. 12 They highlight a central problem in our understanding of the effects of hypoxia by showing a clear neuronal dysfunction in the absence of any measured change in brain ATP concentrations. Thus, 30' exposures to levels of hypoxia which lead to a large slow-wave EEG pattern and in some cases EEG flattening 13 had no effect on cortical or brain stem ATP concentrations; 4,8 on the other hand, pH and phosphocreatine decreased. 1 Furthermore, neurotransmitter metabolism is compromised at the moderate levels of hypoxia that alter cerebral function. 3,5 These studies suggest that decreased ATP is not the cause of cerebral dysfunction in hypoxia. However, there are still reasons for considering the issue as an open one. While observed rates of monoamine and acetylcholine synthesis are depressed directly by hypoxia, 3 ' 5 there is no evidence that the release of neurotransmitter is compromised. Also, ATP measurements are made on whole cortices, which may not reflect concentrations in the sensitive synaptic regions of the brain.The acute effects of anoxia illustrate a similar dilemma in establishing the biochemical basis of cerebral dysfunction. Several groups of workers who have simultaneously measured EEG activity and metabolite changes have noted that EEG activity vanishes at a time when ATP concentration in brain or cortex is decreased by a very small percentage or not at all. 10 Again, while a fall in ATP may not cause the loss in EEG activity, the fact that ATP measurements are not confined to synaptic regions makes it impossible to interpret the results unequivocally.

Effects of mild hypoxia on pilot performances at general aviation altitudes.

“…The brain consumes almost one-fifth of the total oxygen uptake of the body at rest, even though it comprises only 2% of the body's weight (Ernsting, 1988). Lipton and Whittingham (1982) stated that a low oxygen tension condition profoundly disturbs cerebral functioning.…”

High Altitude Cerebral Edema: Cerebral Acute Mountain Sickness

“…In experiments using whole brain slices, Siesjö and colleagues 28 ' 29 demonstrated that ATP concentrations and "energy charge" are not reduced in brain tissue at levels of hypoxia at which brain function is seriously disturbed, suggesting that energy failure is not the main mechanism. However, Lipton and Whittingham 24 have challenged this view by suggesting that ATP depletion may occur in regions of high synaptic density at a time when whole brain ATP depletion is not detectable. They have demonstrated such localized ATP depletion in slices of guinea pig hippocampus.…”