Neurotransmitters and Motor Activity: Effects on Functional Recovery after Brain Injury

Department of Medicine (Neurology), Duke Center for Cerebrovascular Disease, Duke University, Durham, NC 27710, USA.
NeuroRx 11/2006; 3(4):451-7. DOI: 10.1016/j.nurx.2006.07.010
Source: PubMed


There are complex relationships among behavioral experience, brain morphology, and functional recovery of an animal before and after brain injury. A large series of experimental studies have shown that exogenous manipulation of central neurotransmitter levels can directly affect plastic changes in the brain and can modulate the effects of experience and training. These complex relationships provide a formidable challenge for studies aimed at understanding neurotransmitter effects on the recovery process. Experiments delineating norepinephrine-modulated locomotor recovery after injury to the cerebral cortex illustrate the close relationships among neurotransmitter levels, brain plasticity, and behavioral recovery. Understanding the neurobiological processes underlying recovery, and how they might be manipulated, may lead to novel strategies for improving recovery from stroke-related gait impairment in humans.

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    • "The effects of cerebral monoaminergic excesses in the cytotoxic cascade are not understood fully, although in experimental injury models traumatically induced elevations of cerebral serotonin seem to decrease cerebral glucose use,28,29 and serotonin agonists are not particularly helpful in improving post-traumatic neurobehavioral status or TBI outcome.30,31 Administration of catecholamine antagonists impedes recovery from brain injury32-34 and delay emergence from post-traumatic amnesia in humans,35 suggesting that blocking catecholamine excesses is not an effective means by which to mitigate the cytotoxic cascade after TBI. "
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    ABSTRACT: Traumatic brain injury (TBI) is a worldwide public health problem typically caused by contact and inertial forces acting on the brain. Recent attention has also focused on the mechanisms of injury associated with exposure to blast events or explosions. Advances in the understanding of the neuropathophysiology of TBI suggest that these forces initiate an elaborate and complex array of cellular and subcellular events related to alterations in Ca(++) homeostasis and signaling. Furthermore, there is a fairly predictable profile of brain regions that are impacted by neurotrauma and the related events. This profile of brain damage accurately predicts the acute and chronic sequelae that TBI survivors suffer from, although there is enough variation to suggest that individual differences such as genetic polymorphisms and factors governing resiliency play a role in modulating outcome. This paper reviews our current understanding of the neuropathophysiology of TBI and how this relates to the common clinical presentation of neurobehavioral difficulties seen after an injury.
    Dialogues in clinical neuroscience 09/2011; 13(3):287-300.
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    • "A great deal of investigation has focused on pharmacological means of improving long-term motor outcome. To this end, drugs that enhance central noradrenergic activity have shown some promise for promoting motor recovery following brain injury (Berends et al., 2009;Boyeson and Feeney, 1990;Feeney et al., 2004;Goldstein, 2006). "
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    ABSTRACT: Drugs that increase central noradrenergic activity have been shown to enhance the rate of recovery of motor function in pre-clinical models of brain damage. Less is known about whether noradrenergic agents can improve the extent of motor recovery and whether such improvement can be sustained over time. This study was designed to determine if increasing central noradrenergic tone using atipamezole, an alpha-2 adrenoceptor antagonist, could induce a long-term improvement in motor performance in rats subjected to ischemic brain damage caused by permanent middle cerebral artery occlusion. The importance of pairing physical "rehabilitation" with enhanced noradrenergic activity was also investigated. Atipamezole (1 mg/kg, s.c.) or vehicle (sterile saline) was administered once daily on Days 2-8 post-operatively. Half of each drug group was housed under enriched environment conditions supplemented with daily focused activity sessions while the other half received standard housing with no focused activity. Skilled motor performance in forelimb reaching and ladder rung walking was assessed for 8 weeks post-operatively. Animals receiving atipamezole plus rehabilitation exhibited significantly greater motor improvement in both behavioral tests as compared to vehicle-treated animals receiving rehabilitation. Interestingly, animals receiving atipamezole without rehabilitation exhibited a significant motor improvement in the ladder rung walk test but not the forelimb reaching test. These results suggest that a short-term increase in noradrenergic activity can lead to sustained motor improvement following stroke, especially when paired with rehabilitation.
    Brain research 07/2010; 1346:174-82. DOI:10.1016/j.brainres.2010.05.063 · 2.84 Impact Factor
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    • "Research on the physiological underpinnings of movement dynamics has traditionally focused most extensively on the primary motor cortex (M1) pointing out that neurons in M1 are modulated by external dynamic perturbations. Some investigators [10] indicate that several premotor areas feed M1 which then projects to the spinal cord. These areas are intensely interconnected with each other, with a parallel contribution to the control of movement [11]. "
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    ABSTRACT: The disability deriving from stroke impacts heavily on the economic and social aspects of western countries because stroke survivors commonly experience various degrees of autonomy reduction in the activities of daily living. Recent developments in neuroscience, neurophysiology and computational science have led to innovative theories about the brain mechanisms of the motor system. Thereafter, innovative, scientifically based therapeutic strategies have initially arisen in the rehabilitation field. Promising results from the application of a virtual reality based technique for arm rehabilitation are reported.
    Studies in health technology and informatics 02/2009; 145:55-62.
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