Neurotransmitters in Coma, Vegetative and Minimally Conscious States, pharmacological interventions

SummaryArticles on pharmacological interventions in disorders of consciousness after brain damage are increasingly appearing in the medical literature. This hypothesis links disorders of consciousness to the depletion of oxygen reliant neurotransmitters based in two biochemical axes, the amino acid axis (glutamate/GABA) and the monoamine axis (dopamine/noradrenalin and serotonin).After a brain injury, an immediate response inside the brain constitutes a surge of amino acids such as glutamate, GABA and others. Glutamate is excitatory and GABA inhibitory. The inhibitory response dominates and the brain becomes suppressed, leading to a loss in consciousness which reduces oxygen requirements. In time, GABA depletes after increased usage and leakage from the brain into the blood. If it cannot be restored sufficiently in some parts of the brain, a secondary response in these regions occurs which makes GABA receptors oversensitive to GABA, so that decreased GABA levels can maintain their suppressive effect. This occurs in prolonged disorders of consciousness as in the Vegetative State, which can be broken by agents such as zolpidem in some patients. In addition to amino acids, monoamine systems such as dopamine are essential to cognition and motor function. Their depletion or the suppression of brain regions in which they function, are proposed as contributors to disorders of consciousness.Reports of successful arousals after amino acid and monoamine based therapies supports the hypothesis that depletion of these brain chemicals may play a fundamental role in disorders of consciousness.