Restor Neurol Neuros
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Restor Neurol Neuros · Jan 2008
ReviewMechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type specific receptor systems.
Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack of neuronal repair is often associated with significant functional deficits, and depending on the severity of injury, may result in permanent paralysis distal to the site of injury. A detailed understanding of the molecular mechanisms that limit neuronal growth in the injured spinal cord is an important step toward the development of specific strategies aimed at restoring functional connectivity lost as a consequence of injury. ⋯ We speculate that differences in regenerative axonal growth among different fiber systems are a reflection of their intrinsic ability to elongate axons and their distinct cell surface receptor profiles to respond to the growth inhibitory extracellular milieu. The existence of cell type specific mechanisms to impair regenerative axonal growth in the CNS may have important implications for the development of treatment strategies. Depending on the fiber tract injured, different ligand-receptor systems may need to be targeted in order to elicit robust and long-distance regenerative axonal growth.
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Restor Neurol Neuros · Jan 2008
ReviewProteoglycans in the central nervous system: plasticity, regeneration and their stimulation with chondroitinase ABC.
After injury to the mammalian central nervous system (CNS), neurons are not able to regenerate their axons and recovery is limited by restricted plasticity. Axon regeneration is inhibited by the presence of the various inhibitory molecules, including chondroitin sulfate proteoglycans (CSPGs) which are upregulated around the injury site. ⋯ Enzymatic removal of chondroitin sulfate (CS) chains with chondroitinase ABC promotes axon regeneration and reactivates plasticity. This review details the structures and properties of the different CSPGs in the normal and damaged CNS, the use of the enzyme chondroitinase ABC to promote neural regeneration and plasticity, and discusses mechanisms of action and possible therapeutic uses of this enzyme.
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Restor Neurol Neuros · Jan 2006
ReviewStatin-mediated protective effects in the central nervous system: general mechanisms and putative role of stress proteins.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins", are used as cholesterol-lowering agents worldwide. This review, focused on recent experimental and clinical data, summarizes general mechanisms of statin actions underlying neuroprotective effects in the central nervous system (CNS) and presents evidence for putative mechanisms involving heat shock proteins and the survival-related PI-3K/Akt pathway that may be beneficial for the treatment of neurological disorders. ⋯ Available data suggest that statins may be of potential therapeutic use in a variety of diseases of the CNS including ischemic stroke, Alzheimer's disease, multiple sclerosis and some forms of retinal and eye diseases. Before general recommendations can be made and specific therapeutic approaches can be developed, more reliable clinical data and studies are required, and possible side effects must be carefully evaluated.
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Restor Neurol Neuros · Jan 2006
ReviewNeglect and prism adaptation: a new therapeutic tool for spatial cognition disorders.
A large proportion of right-hemisphere stroke patients show unilateral neglect, a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. This spatial cognition disorder affects the orientation of behaviour with a shift of proprioceptive representations toward the lesion side. ⋯ These cognitive effects of prism adaptation suggest that prism adaptation does not act specifically on the ipsilesional bias characteristic of unilateral neglect but rehabilitates more generally the visuo-spatial functions attributed to the right cortical hemisphere. These results reinforce the idea that the process of prism adaptation may activate brain functions related to multisensory integration and higher spatial representations and show a generalization at a functional level. Prism adaptation therefore appears as a new powerful therapeutic tool for spatial cognition disorders.
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Restor Neurol Neuros · Jan 2004
ReviewModulation of motor function and cortical plasticity in health and disease.
Basic science studies demonstrated mechanisms of plasticity and metaplasticity. More recent human studies identified some of these mechanisms as operating in multiple areas of human cognition, such as learning and memory, and in functional recovery from lesions in the CNS, as in stroke. ⋯ Understanding the mechanisms and functional role of human plasticity could lead to the development of therapeutic options in situations in which there is virtually no treatment alternative, as in chronic stroke. We review some of the work performed to better understand the substrates and mechanisms underlying cortical plasticity and discuss some experimental approaches to enhance cortical plasticity and recovery of function, like cortical stimulation.