Coma is a state of unconsciousness that may last for several weeks after brain injury. The eyes remain closed, differentiating it from other consciousness disorders such as the Minimally Conscious or Vegetative State where eyes open and sleep/wake cycles can occur.
In a normally functioning brain, there is a circadian daily utilisation and nightly restoration of neurotransmitter function (1). At night the eyes are closed and neurotransmitter reserves are topped up from their lowered levels during the day in parts of the brain (2-5).
Following brain damage, oxygen and glucose supplies and the production of brain chemicals and neurotransmitters is disrupted. There is a surge of neurotransmitters which can be grouped into arousing (excitatory) and suppressing (inhibitory) ones, including glutamate (excitatory) and GABA (inhibitory) (6- 8). The inhibitory GABA acts by suppressing and protecting vulnerable brain cells from anoxic and ischaemic surroundings. The excitotoxic glutamate has been proposed to stimulate potentially suicidal (apoptic) brain cells to absorb toxic metabolites in the unfavourable microenvironment (9). Inhibition dominates, leading to a loss of consciousness. The surge of excitatory and inhibitory neurotransmitters is followed by a subsequent depletion of these chemicals in the brain. This is made worse when chemicals such as GABA leak through the blood brain barrier into the blood, early after brain damage (10).
Following neurotransmitter depletion after brain damage, some patients remain unconscious in Coma with their eyes closed for several weeks before they can move onto higher consciousness states such as the Vegetative, Minimally Conscious, or fully conscious state. This progression presumably occurs when neurotransmitters, depleted after brain damage, have now been restored to more appropriate levels in cortical and sub cortical brain regions (9).
Zolpidem is not known to be effective shortly after brain damage. However, in the long term (after more than 6 months) in the Minimally Conscious or Vegetative State it has been shown to be effective. This is possibly due to the reversal of a condition called neurodormancy, a proposed long term protective suppressive mechanism after brain damage.
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4 Grimes MA, Cameron JL and Fernstrom JD, Cerebrospinal fluid concentrations of large neutral and basic amino acids in Macca mulatta: diurnal variations and responses to chronic changes in dietary protein intake, Metabolism 2009, 58: 129-40.
5 Marquez de Prado B, Castaneda TR, Galindo A, DedArco A, Segovia G, Reiter RJ and Mora F, Melatonin disrupts circadian rythms of glutamate and GABA in the neostriatum of the awake rat: a microdialysis study, Journal of Pineal research, 2000, 29: 209-16.
6 Nilsson GE and Lutz PL, Release of inhibitory neurotransmitters in response to anoxia in turtle brain, Am.J.Physiol Reg. Integ. Comp. Physiol. 1991, 261: R32-R37.
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9 Clauss RP. Neurotransmitters in Coma, Vegetative and Minimally Conscious State, pharmacological interventions.Medical Hypotheses, March 2010.
10 Suzuki M Kudo A, Sugawara A, Yoshida K, Kubo Y, Suzuki T, Ogasawara K, Doi M and Ogawa A, Amino acid concentrations in the blood of the jugular vein and peripheral artery alter traumatic brain injury: decreased release of glutamate into the jugular vein in the early phase, J Neurotrauma 2002, 19: 285- 92.
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