Pritam Dutta  M.Optom, FAAO

ERC Eye Hospital Sibsagar, Assam, India



Due to the anatomic features of the dopaminergic system, dopamine pathways appear to be particularly sensitive to brain injury among the neurotransmitter systems. Both dopaminergic cell death and metabolic abnormalities of the dopaminergic system are seen in Traumatic Brain Injury (TBI) animal models. (1) There is compelling evidence that dopamine disruption contributes to post-TBI impairments, and that dopaminergic modulation may have important neuroprotective properties. Because dopamine affects numerous brain regions, including the hippocampus, striatum, and frontal cortex (FC), targeting dopamine signaling in TBI could be extremely beneficial. Damage to these regions has been linked to cognitive failure in TBI. (2-6) Furthermore, TBI has been linked to variations in dopamine levels.(7)

TBI affects several brain regions, including the FC, hippocampus, and striatum.(4-6) These three areas are very essential because they play a role in learning, memory, executive function, and attention, and they may be affected by a TBI.(8,9) Damage to brain tissue following a TBI, on the other hand, is not limited to specific brain regions. The clinical picture of TBI is further complicated by diffuse axonal injury in white matter tracts, as well as grey matter damage.(10,11) Dopamine, whether depleted or overexpressed, can induce severe cellular dysfunction; hence, changes in dopamine levels and corresponding abnormalities in dopaminergic systems could have a significant impact on functional results [Fig 1].


Figure 1: Changes in the dopamine levels and functional outcome following TBI.


Dopamine release changes following TBI

The nucleus accumbens (NAC), which has an inner core and an outside shell with very diverse roles, is a significant site of dopamine activity. If discrepancies in dopamine release patterns are linked to TBI symptoms like cognitive impairment, which is influenced by different regions of the NAC, differences in dopamine physiology between the core and shell are likely to have significant clinical ramifications.(12) However; more study into the effect of TBI on stimulus-related dopamine dynamics in distinct regions of the NAC is needed. Chen et al. found that TBI was linked to significant alterations in dopamine release in both the core and shell of the NAC, with the core being slightly more sensitive to TBI-related changes.(12) Furthermore, their findings showed that the most severe changes in dopamine dynamics happened within the first two weeks following damage, with modest recovery over time. These electrochemical findings in NAC could help to elucidate the mechanisms underlying post-TBI psychological disorders and justify the use of dopaminergic modulation as a clinical treatment for TBI.

Changes in dopamine receptor expression following TBI

Dopamine receptors are classified into five subtypes: D1, D2, D3, D4 and D5. Dopamine receptors are classified as D1-class (D1 and D5), which are mostly found in the kidney, heart, and mesenteric tissue, or D2-class (D2, D3, and D4), which are mostly found in presynaptic adrenergic nerve endings and sympathetic ganglia. (13,14) Transient mechanical violence acts on the neural system during TBI, causing neuronal hyperexcitability, calcium channel opening, and activation of dopaminergic neurons, which results in dopamine release.(15) Calcium channel activation increases tyrosine hydroxylase (TH) activity in neurons, and TH activation speeds up dopamine synthesis in dopaminergic neurons, resulting in a substantial quantity of dopamine build up. Calcium channel activation may thus influence dopamine levels. It’s been established that dopamine D1 receptor activation can affect calcium channel currents in a modulatory manner.(16) Thus, transient reductions in dopamine D1 receptor binding have been observed in the early aftermath of injury, although they do not last long.(17)



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