Mark Bayley MSc MD FRCPC, Shannon Janzen MSc, Rachel Anderson BSc, Joanne Aubut BSc, Andrea Lee, Robert Teasell MD FRCPC
For a number of years, it has been recognized that brain injury causes alterations in neurotransmitter levels through a number of pathways including direct neuronal trauma, changes in neuronal membranes, and through secondary injury such as alterations in cerebral perfusion. A number of both clinical and basic science researchers have attempted to find pharmacological treatments in an attempt to normalize neurotransmitter levels and enhance brain recovery.
The neurotransmitters of interest include serotonin (5-hydroxytryptophan or 5-HT), acetylcholine, gamma-aminobutyric acid (GABA), and catecholamines such as dopamine and norepinephrine (NE). There are many subtypes of serotonin receptors and medications that have affinity for 5-HT1a, 1b, and 1c, which tend to reduce aggression in humans and have effects on sleep, mood, and behaviour. Acetylcholine is most associated with memory in the central nervous system (CNS), but may have other effects. It is synthesized from choline in neurons and is degraded mostly by acetylcholinesterase at the synapse. GABA and glycine are inhibitory neurotransmitters found throughout the CNS. GABAA receptors affect chlorine channels and hyperpolarize nerve cell membranes. Therefore, the neuron is less likely to activate. GABAB receptors enhance potassium or decrease calcium conductance across the cell membrane.
The catecholamines dopamine and NE tend to stimulate target receptors. Dopamine has diffuse effects on the CNS and is involved with motor control, arousal, procedural learning, and cognition. There are at least five dopamine receptor variants and abnormalities. The D2 variant is implicated in Parkinson’s disease and the D4 variant in schizophrenia. The effects of NE are associated with sleep regulation, mood, aggression, and perception of sensation. It results from the conversion of tyrosine into dopamine and then into NE.
This module provides an overview of the medications that have been used in brain injury to enhance recovery of a number of brain functions. Most of these medications’ effects are believed to be mediated through alterations in the neurotransmitters mentioned above. The module is organized to provide clinicians with evidence of pharmacological interventions for a number of clinically relevant problems after brain injury.
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