The CNS lesion scar: new vistas on an old regeneration barrier

Stichel, Christine C.; Müller, Hans

doi:10.1007/s004410051151

Cited by 229 publications

(157 citation statements)

References 63 publications

(75 reference statements)

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“…These obstacles are: (i) scar tissue formation after tissue injury (1-7); (ii) gaps in nervous tissue formed during phagocytosis of dying cells after injury (3,(8)(9)(10)(11)(12)(13)(14); (iii) factors that inhibit axon growth in the mature mammalian CNS (1,3,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20); and (iv) failure of many adult neurons to initiate axonal extension (3, 8-12, 15, 17, 21, 22). In this paper, we describe the creation of a permissive environment for axonal regrowth using a synthetic biological nanomaterial that self assembles in vivo, with components that break down into beneficial building blocks and produce no adverse effects on the CNS.…”

mentioning

confidence: 99%

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Ellis-Behnke

Liang

You

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

753

490

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Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. To achieve axonal regeneration after injury in the CNS, several formidable barriers must be overcome, such as scar tissue formation after tissue injury, gaps in nervous tissue formed during phagocytosis of dying cells after injury, and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment for axons not only to regenerate through the site of an acute injury but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a previously undiscovered nanobiomedical technology for tissue repair and restoration but also raises the possibility of effective treatment of CNS and other tissue or organ trauma.

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mentioning

confidence: 99%

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Ellis-Behnke

Liang

You

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

753

490

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“…Typically in mammals, there is a subsequent proliferation and hypertrophy of astrocytes around the injury site. 8,9,48,71 . Specifically, reactive astrogliosis is denoted by increased immunoreactivity of glial fibrillary acid protein (GFAP), which is a distinct cellular marker of astrocytes.…”

Section: Experimental Modelsmentioning

confidence: 99%

“…Specifically, reactive astrogliosis is denoted by increased immunoreactivity of glial fibrillary acid protein (GFAP), which is a distinct cellular marker of astrocytes. 14,48,[71][72][73][74]111 It has been demonstrated that reactive adult astrocytes upregulate the production of laminin and neurotrophin C. 75,76 In addition to the endogenously present myelinassociated neurite growth inhibitory constitutents, reactive astrocytes form an astroglial scar that acts as a physical and/or chemical barrier to axonal regeneration. 8,35,72,77,78 Proximity to the lesion epicentre determines whether the reactive glial environment will be growth supportive or inhibitory.…”

Section: Experimental Modelsmentioning

confidence: 99%

“…63 Although the functional role of glial scarring is not completely understood, it has been suggested to be an attempt by the CNS to restore homeostasis through isolation of the damaged region. 71,74,79 Activated astrocytes upregulate expression of various cell surface molecules including cell adhesion molecules and extracellular matrix proteins.…”

Section: Experimental Modelsmentioning

confidence: 99%

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Post-traumatic inflammation following spinal cord injury

2003

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“…2,10 Although di erent glial cells participate in the scar formation, the reactive astrocytes play a predominant role re¯ected by the very high levels of glial acid ®brillary protein (GFAP). 11 A landmark of secondary tissue loss following CNS trauma is a devastating decrease of intracellular energy substrates. 12 This energy loss is due to vascular damage and the subsequent reperfusion induced endothelium damage.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of oral creatine supplementation on spinal cord injury in rats

et al. 2002

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Study design: To evaluate a potential protective e ect of increased creatine levels in spinal cord injury (SCI) in an animal model. Objectives: Acute SCI initiates a series of cellular and molecular events in the injured tissue leading to further damage in the surrounding area. This secondary damage is partly due to ischemia and a fatal intracellular loss of energy. Phospho-creatine in conjunction with the creatine kinase isoenzyme system acts as a potent intracellular energy bu er. Oral creatine supplementation has been shown to elevate the phospho-creatine content in brain and muscle tissue, leading to neuroprotective e ects and increased muscle performance. Setting: Zurich, Switzerland. Methods: Twenty adult rats were fed for 4 weeks with or without creatine supplemented nutrition before undergoing a moderate spinal cord contusion. Results: Following an initial complete hindlimb paralysis, rats of both groups substantially recovered within 1 week. However, creatine fed animals scored 2.8 points better than the controls in the BBB open ®eld locomotor score (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed that in all rats a cavity had developed which was comparable in size between the groups. In creatine fed rats, however, a signi®cantly smaller amount of scar tissue surrounding the cavity was found. Conclusions: Thus creatine treatment seems to reduce the spread of secondary injury. Our results favour a pretreatment of patients with creatine for neuroprotection in cases of elective intramedullary spinal surgery. Further studies are needed to evaluate the bene®t of immediate creatine administration in case of acute spinal cord or brain injury.

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The CNS lesion scar: new vistas on an old regeneration barrier

Cited by 229 publications

References 63 publications

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

Post-traumatic inflammation following spinal cord injury

Protective effects of oral creatine supplementation on spinal cord injury in rats

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