Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPET study using 123I-β-CIT and 123I-IBZM

Abstract

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (+/-SD) at the time of head trauma was 5.8+/-4.2. SPET was performed on average 141 days (SD +/-92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar beta-CIT and IBZM binding ratios (P< or =0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Delayed increase of tyrosine hydroxylase expression in rat nigrostriatal system after traumatic brain injury

“…Evidence that dopamine systems are altered in humans following TBI is based on reports that neurostimulants, including dopamine agonists, can be beneficial in attenuating cognitive deficits (Goldstein, 2003;McAllister et al, 2004) and data showing altered dopamine transporter binding (Donnemiller et al, 2000). After experimental TBI, alterations in the catecholamine systems have been found in various brain regions and have been shown to be time-dependent (Dunn-Meynell et al, 1994;McIntosh et al, 1994).…”

Call for an Integrative and Multi-Disciplinary Approach to Traumatic Brain Injury (TBI)

“…Clinical evidence that dopamine systems are altered following TBI is based on the consistent findings that catecholaminergic stimulants, as methylphenidate, and dopaminergic agonists, amantadine and bromocriptine, attenuate the cognitive deficits in attention, information processing speed, working memory, and executive functioning associated with TBI (Warden et al, 2006;Wheaton et al, 2009) and SPECT imaging data showing a decrease in dopamine transporters in the striatum of severe TBI patients 4 -5 months post-injury (Donnemiller et al, 2000). Deficiencies in dopaminergic transmission may underlie, at least in part, the chronic affective, motivational and emotional changes with TBI.…”

Rehabilitation Considerations for Traumatic Brain Injury in the Geriatric Population: Epidemiology, Neurobiology, Prognosis, and Management

“…These patients also may be at risk for worse outcomes secondary to multiple mechanisms of insult associated with the already depleted dopamine (DA) neurotransmitter systems that occur with PD [55]. Following TBI, there are changes in CNS-DA levels secondary to multiple mechanisms [56,57]. Long-term changes in DA transporter (DAT) expression, as well as changes in other DA system proteins, are seen within the cortex and striatum [58][59][60].…”