Silencing the brain may be better than stimulating it. The GABA effect.

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.

• Authors: Francesca Pistoia, Marco Sarà, Simona Sacco, Marco Franceschini, Antonio Carolei
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 20 Issue 26 Pg. 4154-66 ( 2014) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 24025066 (Publication Type: Journal Article, Review)

Chemical References

• Central Nervous System Depressants
• GABA Agents

Topics

• Brain Injuries (complications, drug therapy)
• Central Nervous System Depressants (pharmacology, therapeutic use)
• Consciousness Disorders (complications, drug therapy)
• GABA Agents (pharmacology, therapeutic use)
• Humans