Axonal elongation into PNS “bridges” after CNS injury in adult rats

McGill University, Montréal, Quebec, Canada
Science (Impact Factor: 33.61). 11/1981; 214(4523):931-3. DOI: 10.1126/science.6171034
Source: PubMed


The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.


Available from: Albert J. Aguayo
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    • "system (CNS) become obvious: While neurons of the PNS reveal a significant degree of regeneration after injury, such regenerative neuronal growth generally fails after an injury of the adult CNS although central neurons have some, but very limited, inherent regenerative capacity (David and Aguayo, 1981). The regenerative failure after CNS trauma and neurodegeneration, therefore, cannot be attributed to just one single cause, and the reasons for the difference in the regenerative responses of PNS and CNS are manifold (Ferguson and Son, 2011) including (i) the presence of myelin-associated inhibitors, (ii) a slower rate of degeneration of the distal segment of the injured fiber tract, (iii) a generally slower axonal growth rate, and (iv) the inhibitory influences of the glial and the extracellular environment. "
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    ABSTRACT: The consequence of numerous neurological disorders is the significant loss of neural cells, which further results in multilevel dysfunction or severe functional deficits. The extracellular matrix (ECM) is of tremendous importance for neural regeneration mediating ambivalent functions: ECM serves as a growth-promoting substrate for neurons but, on the other hand, is a major constituent of the inhibitory scar, which results from traumatic injuries of the central nervous system. Therefore, cell and tissue replacement strategies on the basis of ECM mimetics are very promising therapeutic interventions. Numerous synthetic and natural materials have proven effective both in vitro and in vivo. The closer a material's physicochemical and molecular properties are to the original extracellular matrix, the more promising its effectiveness may be. Relevant factors that need to be taken into account when designing such materials for neural repair relate to receptor-mediated cell-matrix interactions, which are dependent on chemical and mechanical sensing. This chapter outlines important characteristics of natural and synthetic ECM materials (scaffolds) and provides an overview of recent advances in design and application of ECM materials for neural regeneration, both in therapeutic applications and in basic biological research.
    Progress in brain research 11/2014; 214:391-413. DOI:10.1016/B978-0-444-63486-3.00016-5 · 2.83 Impact Factor
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    • "Compared to the peripheral nervous system, the failure of the adult CNS to regenerate is largely attributed to two basic aspects: inhibitory environmental influences and decreased growth capabilities of adult CNS neurons. Since early demonstration of successful growth of injured CNS axons into grafted peripheral nerve (David and Aguayo, 1981), multiple CNS axonal growth inhibitory factors have been identified and are mainly associated with degenerating CNS myelin (such as Nogo, MAG, OMgp) and with glial scar (such as chondroitin sulfate proteoglycans, CSPGs) (Yiu and He, 2006). However, blockade of these extracellular inhibitory signals alone is often insufficient for the majority of injured axons to achieve long-distance regeneration, as intrinsic regenerative capacity of mature CNS neurons is also a critical determinant for axon re-growth(Sun et al., 2011). "

    Neural Regeneration Research 10/2014; 9(19):1703-1705. DOI:10.4103/1673-5374.143412 · 0.22 Impact Factor
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    • "The limited ability of the human central nervous system (CNS) to repair itself following injuries has been known since the days of Ancient Egypt (3,000–2,5000 BCE), as documented in the Edwin Smith papyrus [1]. It had long been thought that neurons in the CNS were incapable of mounting a regenerative response, until the studies of Aguayo and colleagues in the early 1980's [2] [3] which demonstrated that certain classes of neurons within the CNS, particularly those neurons which sustained an axonal injury in close proximity to their cell body, were able to regenerate their axons within a permissive environment, such as a peripheral nerve graft. Aguayo's work and more recent studies [4] [5] [6] have all demonstrated that supraspinal neurons (neurons arising in the cerebral cortex or brainstem and which project their axons caudally into the spinal cord) are actually capable of mounting a regenerative, albeit brief, and response following injury, when provided with the proper environment. "
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    ABSTRACT: Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration.
    BioMed Research International 09/2014; 2014:845323. DOI:10.1155/2014/845323 · 2.71 Impact Factor
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