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

ABSTRACT 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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    • "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
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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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    • "Agents with noradrenergic-attenuating effects (eg, clonidine) sometimes also are used for these and other purposes. Animal models suggest , however, that dopamine and norepinephrine antagonists delay neuronal recovery and impair neuronal plasticity [69] [70] [125] [126]. Among persons with TBI, typical antipsychotics exacerbate cognitive impairments [127] and may prolong the period of PTA [72]. "
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    ABSTRACT: Traumatic brain injury (TBI) results in approximately 230,000 hospitalizations annually in the United States. Advances in the acute management of TBI have improved survival after TBI. Many TBI survivors develop neurobehavioral disturbances in the acute post-injury period. Neurobehavioral sequelae present clinical management challenges for critical care professionals. This article defines and describes TBI and reviews its common neuroanatomic and neurobehavioral consequences. These disturbances are organized under the framework of posttraumatic encephalopathy, and the characteristic forms and stages of recovery of this condition are discussed. Recommendations regarding evaluation and management of posttraumatic neurobehavioral problems in the critical care setting are offered.
    Critical Care Clinics 11/2008; 24(4):737-65, viii. DOI:10.1016/j.ccc.2008.06.001
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