Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine (DA) physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after traumatic brain injury (TBI). Alterations in DA levels can lead to oxidative stress and cellular dysfunction, and DA plays an important role in central nervous system inflammation. Therapeutic targeting of DA pathways may offer benefits for both neuronal survival and functional outcome after TBI. The purpose of this review is to discuss the role of DA pathology in acute TBI and the potential impact of therapies that target these systems for the treatment of TBI.

No abstract

To investigate the role of dopamine release in cognitive impairment and motor learning deficits after brain injury, different levels of traumatic brain injury (TBI) were made in rats by using fluid percussion at two different atmospheres (2 Psi and 6 Psi). Tonic and phasic bursting dopamine release and behavior tests followed at several time points. We used in vitro fast-scan cyclic voltammetry to survey dopamine release in the striatum and analyzed the rats' behavior using novel object recognition (NOR) and rotarod tests. Both tonic and bursting dopamine release were greatly depressed in the severely (6 Psi) injured group, which persisted up to 8 weeks later. However, in the 2 Psi-injured group, the suppression of bursting dopamine release occurred at 1~2 weeks after injury, but there were no significant differences after 4 weeks. Tonic dopamine release was also diminished significantly at 1~2 weeks after the injury; partial recovery could then be seen 4 weeks after injury. A significant deficiency in the fixed speed rotarod test and NOR test were noted in both 2 Psi and 6 Psi groups initially; however, the changes recovered in the 2 Psi group 2 weeks after injury while persisting in the 6 Psi group. In conclusion, striatal evoked dopamine release was affected by fluid percussion injury, with behavioral deficits showing differences as a function of injury severity. The severe fluid percussion injury (6 Psi) group showed more dopamine release defects, as well as cognitive and motor deficiencies. Recovery of dopamine release and improvement in behavioral impairment were better in the mild TBI group.

No abstract

Objective: To investigate the effects of systemic inflammation in the critical postnatal stages on neurophysiological actions of immune processes and neural plasticity in adult rats after kainic acid (KA)-induced seizures. Methods: To determine changes in hippocampal synaptic plasticity after postnatal central nervous system inflammatory responses and seizure attacks, we performed intraperitoneal injections of lipopolysaccharide (LPS) in postnatal Sprague Dawley rats on day 14 (P14) to induce central nervous system inflammation. We then used a KA tail vein injection on P35 to induce seizure attacks. We compared the variability in synaptic plasticity in the hippocampal Schaffer collateral-CA1 region of seizure animals with or without LPS-induced inflammation preconditioning. Results: P14 injection of LPS increased susceptibility to seizures, while treatment with KA on P35 induced seizures. Long-term potentiation (LTP) of the Schaffer collateral-CA1 region was impaired in seizure animals, and this effect was more pronounced in the P14 LPS injection group. Fluoro-Jade staining revealed an increase in degenerated hippocampal CA1 pyramidal cells in the P14 LPS injection group. Cytokine expression in the hippocampus in the pre-, peri- and postictus periods was greater in P14 LPS rats than in saline-treated rats. Conclusions: Intraperitoneal LPS injection on P14 induces higher cytokine secretion after KA-induced seizures, enhancing neuronal excitability, shortening seizure onset time and exacerbating neuronal degeneration and impairment of LTP formation in the hippocampal Schaffer collateral-CA1 region. Central nervous system inflammation during critical stages of childhood development could disrupt the balance needed for neurophysiological actions of immune processes, producing direct, pernicious effects on memory, neural plasticity and neurogenesis into adulthood.