How the Brain Works

Signalling in the brain during illness and after injury

We know from studies of astroglia cells in cell cultures that these cells, after injury, reduce their ability to affectively handle glutamate. As a result, some glutamate remains in the synapse region after signalling has occurred, which in turn leads to more nonspecific activation of the nerve cells. Another consequence is that less glutamate enters the astrocytes. This is problematic because astrocytes use glutamate to produce new energy and also to produce glutamine, which is delivered to the nerve cells to produce new glutamate for continued signalling. In addition the astrocytes swell.

Although studies of brain metabolism are not fully established after illness or injury, it seems that immediately after an injury, the brain needs more energy for the healing processes, but the energy supply decreases over time after the injury. If this is the whole truth, it means that the brain’s signalling system does not function normally during illness and injury. You simply get a lack of available energy and thus also decreased efficiency in the signalling between the brain cells.

Many data from experimental systems and studies in humans suggest that dopamine signalling decreases in several brain areas following a brain injury. Dopamine has to do with the ability to move, but dopamine in the frontal parts of the brain, are also involved in cognitive functions including concentration and attention. This means that reduced dopamine signalling in the front parts of the brain leads to impaired concentration capacity and decreased attention which are some core symptoms of brain fatigue. Support for dopamine involvement in brain fatigue is that raising the dopamine content by treatment with methylphenidate and other dopamine stimulators leads to increased concentration capacity and better attention.

It has long been known that serotonin is important for emotional life. Serotonin levels are lowered during depression and anti-depressant drugs seem to work by increasing the serotonin levels in the synapses. After a brain injury, it also appears that serotonin levels decrease in several brain areas, which could explain the effect on lability and irritability that often occurs in brain-tired individuals. Very low doses of anti-depressant drugs can alleviate these symptoms, which may be an additional support for the serotonin’s involvement in the brain fatigue problem. 

Other signalling substances, such as norepinephrine and acetylcholine, also appear to decrease after brain damage. Some effects on brain fatigue have been achieved by adding these substances in drug form, though some results are not so positive.