Title:Silencing the Brain May be Better than Stimulating it. The GABA Effect
Volume: 20
Issue: 26
Author(s): Francesca Pistoia, Marco Sara, Simona Sacco, Marco Franceschini and Antonio Carolei
Affiliation:
Keywords:
Disorders of consciousness, vegetative state, minimally conscious state, GABA.
Abstract: Cases of recovery from vegetative and minimally conscious state after the administration of various pharmacological agents
have been recently reported. These agents include CNS depressants (zolpidem, baclofen, lamotrigine) and CNS stimulants (tricyclic antidepressants,
selective serotonin reuptake inhibitors, dopaminergic agents, methylphenidate). The action of CNS depressants as awakening
agents sounds paradoxical, as they are commonly prescribed to slow down brain activity in the management of anxiety, muscle tension,
pain, insomnia and seizures. How these drugs may improve the level of consciousness in some brain-injured patients is the subject of intense
debate. Here we hypothesize that CNS depressants may promote consciousness recovery by reversing a condition of GABA impairment
in the injured brain, restoring the normal ratio between synaptic excitation and inhibition, which is the prerequisite for any transition
from a resting state to goal-oriented activities (GABA impairment hypothesis). Alternative or complementary mechanisms underlying
the improvement of consciousness may include the reversal of a neurodormant state within areas affected by diaschisis (diaschisis
hypothesis) and the modulation of an informative overload to the cortex as a consequence of filter failure in the injured brain (informative
overload hypothesis). A better understanding of how single agents act on neural networks, whose functioning is critical for recovery, may
help to advance a tailored pharmacological approach in the treatment of severely brain injured patients.
