| Title & Author | Abstract | |
|---|---|---|
| 10(026) | THE BIOCHEMICAL BASIS OF COMA
Target Article on Coma-Biochemistry John Smythies Division of Neurochemistry Brain and Perception Laboratory Center for Brain and Cognition University of California, San Diego La Jolla CA 92093-0109 and Department of Neuropsychiatry Institute of Neurology Queen Square, London smythies@psy.ucsd.edu |
Abstract:
Current research on the neural basis of consciousness is
based mainly on neuroimaging, physiology and psychophysics. This
target article reviews what is known about biochemical factors that
may contribute to the development of consciousness, based on loss
of consciousness (i.e., coma). There are two theories of the
biochemical mode of action of general anaesthetics. One is that
anaesthesia is a direct (i.e., not receptor-mediated) effect of the
anaesthetic on cellular neurophysiological function; the other is
that some alteration of receptor function occurs. General
anaesthetics are mainly GABA agonists but some (such as ketamine)
are glutamate antagonists. They also affect other systems,
particularly cholinergic ones. There are various comas of metabolic
origin. For example, a combination of small doses of the iron
chelators desferrioxamine and prochlorperazine induce a profound
and long lasting coma in humans. The mechanisms that might mediate
this include redox mechanisms at the glutamate synapse,
post-synaptic endocytosis of dopamine and iron, and intracellular
iron-dopamine complexes, which are powerful dismuters of the
superoxide anion. New findings in cell biology relating to
endocytosis and recycling of receptors are discussed in a wider
context. These biochemical events may induce coma by two
mechanisms: (i) Consciousness may depend on widespread cortical (or
cortico-thalamic) activation. (ii) Whereas these biochemical
changes are widespread, only the changes in a subset of
'consciousness' neurons may count. An experimental program to
distinguish between these two alternatives is proposed.
Keywords: anaesthetics, coma, consciousness, desferrioxamine dopamine, GABA, general glutamate iron, redox mechanisms, synapses |
| 11(031) | NEUROBIOCHEMISTRY OF COMA: MONOAMINERGIC SYSTEM INTERACTIONS
Commentary on Smythies on Coma-Biochemistry Jiankang Liu Division of Biochemistry and Molecular Biology University of California, Berkeley CA 94720-3202 and Children's Hospital Oakland Research Institute Oakland, CA 94609-1673 jiank@uclink4.berkeley.edu |
Abstract:
All neurotransmitters may be involved in coma, with
interactions between receptor-mediated and non-receptor-mediated
functions.
Keywords: anaesthetics, coma, consciousness, desferrioxamine dopamine, GABA, general glutamate iron, redox mechanisms, synapses |
| 11(032) | CRUCIAL ROLE OF IRON IN ANESTHESIA
Commentary on Smythies on Coma-Biochemistry Richard M. Kostrzewa Department of Pharmacology Quillen College of Medicine East Tennessee State University PO Box 70, 577 Johnson City, TN 37614. http://www2.etsu.edu/HTBIN/PH/nameserver/105 Kostrzew@ETSU.edu |
Abstract:
Despite the consensus that glutamatergic and GABAergic
imbalance is likely to be involved in anesthesia or coma, there is
little known about molecular mechanisms of action of gaseous
anesthetics. The target article by Smythies (1999) is engagingly
analytical and insightful, proposing novel and testable hypotheses
for the molecular mechanisms of action of anesthetics as well as for
processes that may be involved in coma. The most creative and
convincing of his hypotheses concerns the crucial role of iron in
maintaining neural respiration and energy production as well as its
involvement in synaptic plasticity. Smythies' paper is certain to
stimulate new ideas and experiments on the molecular mechanisms of
anesthesia and coma.
Keywords: anaesthetics, coma, consciousness, desferrioxamine dopamine, GABA, general glutamate iron, redox mechanisms, synapses |