REPAIR AND RECOVERY FOLLOWING SPINAL CORD INJURY IN A NEONATAL MARSUPIAL (<i>MONODELPHIS DOMESTICA</i>)

Saunders, Norman; Deal, A; Knott, Graham; Varga, Zoltán; Nicholls, John G.

doi:10.1111/j.1440-1681.1995.tb02060.x

Cited by 49 publications

(46 citation statements)

References 25 publications

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“…Indeed, we found that, in the absence of both IF proteins, astrocytes were morphologically immature (16,25). It is well known that, in the immature CNS, regenerating fibers can grow through lesions (26). This phenomenon seems to be due in part to decreased glial scar formation, thus creating a permissive environment for axonal regeneration (27).…”

Section: Discussionmentioning

confidence: 67%

Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

Menet

Prieto

Privat

et al. 2003

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

285

195

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The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional disabilities. The inability of neurons to regenerate their axon is appreciably due to an inhospitable environment made of an astrocytic scar. We generated mice knock-out for glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, which are upregulated in reactive astrocytes. These animals, after a hemisection of the spinal cord, presented reduced astroglial reactivity associated with increased plastic sprouting of supraspinal axons, including the reconstruction of circuits leading to functional restoration. Therefore, improved anatomical and functional recovery in the absence of both proteins highlights the pivotal role of reactive astrocytes in axonal regenerative failure in adult CNS and could lead to new therapies of spinal cord lesions.

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Section: Discussionmentioning

confidence: 67%

Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

Menet

Prieto

Privat

et al. 2003

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

285

195

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“…Another of the more exciting developmental models of SCI was developed by an Australian group led by Dr Norman Saunders and has been used extensively to study the unique capacity of the immature spinal cord to regenerate after SCI (37). In this model, the neonatal opossum, Monodelphis domestica, undergoes complete spinal cord transection by a microscalpel in the midthoracic region (T4-T6).…”

Section: Review Of Animal Modelsmentioning

confidence: 99%

Pediatric Spinal Cord Injury in Infant Piglets: Description of a New Large Animal Model and Review of the Literature

Kuluz

Samdani

Benglis

et al. 2010

The Journal of Spinal Cord Medicine

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Objective: To develop a new, clinically relevant large animal model of pediatric spinal cord injury (SCI) and compare the clinical and experimental features of pediatric SCI. Methods: Infant piglets (3-5 weeks old) underwent contusive SCI by controlled cortical impactor at T7. Severe complete SCI was induced in 6 piglets, defined as SCI with no spontaneous return of sensorimotor function. Eight piglets received incomplete SCI, which was followed by partial recovery. Somatosensory evoked potentials, magnetic resonance imaging, neurobehavioral function, and histopathology were measured during a 28-day survival period. Results: Mean SCI volume (defined as volume of necrotic tissue) was larger after complete compared with incomplete SCI (387 ± 29 vs 77 ± 38 mm 3 , respectively, P , 0.001). No functional recovery occurred after complete SCI. After incomplete SCI, piglets initially had an absence of lower extremity sensorimotor function, urinary and stool retention, and little to no rectal tone. Sensory responses recovered first (1-2 days after injury), followed by spontaneous voiding, lower extremity motor responses, regular bowel movements, and repetitive flexion-extension of the lower extremities when crawling. No piglet recovered spontaneous walking, although 4 of 8 animals with incomplete injuries were able to bear weight by 28 days. In vivo magnetic resonance imaging was performed safely, yielded high-resolution images of tissue injury, and correlated closely with injury volume seen on histopathology, which included intramedullary hemorrhage, cellular inflammation, necrosis, and apoptosis. Conclusion: Piglets performed well as a reproducible model of traumatic pediatric SCI in a large animal with chronic survival and utilizing multiple outcome measures, including evoked potentials, magnetic resonance imaging, functional outcome scores, and histopathology.

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“…The exact time at which regeneration ceases varies from species to species (1)(2)(3)(4)6) and within an animal, depending on the maturity of the tract that has been disrupted (7)(8)(9)33). Eventually all CNS regeneration fails except in the olfactory system.…”

mentioning

confidence: 99%

Myelin-associated neurite growth-inhibitory proteins and suppression of regeneration of immature mammalian spinal cord in culture.

Varga

Schwab

Nicholls

1995

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

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Neurite outgrowth across spinal cord lesions in vitro is rapid in preparations isolated from the neonatal opossum Monodelphis domestica up to the age of 12 days. At this age oligodendrocytes, myelin, and astrocytes develop and regeneration ceases to occur. The role of myelin-associated neurite growth-inhibitory proteins, which increase in concentration at 10-13 days, was investigated in culture by applying the antibody IN-1, which blocks their effects. In the presence of IN-1, 22 out of 39 preparations from animals aged 13-17 days showed clear outgrowth of processes into crushes. When 34 preparations from 13-day-old animals were crushed and cultured without antibody, no axons grew into the lesion. The success rate with IN-1 was comparable to that seen in younger animals but the outgrowth was less profuse. IN-1 was shown by immunocytochemistry to penetrate the spinal cord. Other antibodies which penetrated the 13-day cord failed to promote fiber outgrowth. To distinguish between regeneration by cut neurites and outgrowth by developing uncut neurites, fibers in the ventral fasciculus were prelabeled with carbocyanine dyes and subsequently injured. The presence oflabeled fibers in the lesion indicated that IN-1 promoted regeneration. These results show that the development of myelin-associated growthinhibitory proteins contributes to the loss of regeneration as the mammalian central nervous system matures. The definition of a critical period for regeneration, coupled with the ability to apply trophic as well as inhibitory molecules to the culture, can permit quantitative assessment of molecular interactions that promote spinal cord regeneration.As the central nervous system (CNS) matures in embryonic and neonatal mammals, a sharp decrease occurs in the ability of nerve fibers to grow across spinal cord lesions, to effect repair, and to restore functions (1-5). The exact time at which regeneration ceases varies from species to species (1-4, 6) and within an animal, depending on the maturity of the tract that has been disrupted (7-9, 33). Eventually all CNS regeneration fails except in the olfactory system. Several new strategies have been developed with the aim of prolonging the capacity for regeneration and restoration of function after lesions in adult CNS. These include the use of grafts of peripheral nerve (10, 11), embryonic tissue (12-14), and Schwann cells (15, 16), as well as the application of trophic molecules such as neurotrophin 3 (17) to promote fiber outgrowth across CNS lesions or brain-derived neurotrophic factor to promote survival of axotomized cells (18).In pathways that become myelinated there is a correlation with the development of myelin and the appearance of myelinassociated inhibitory proteins known as NI-35/250 that prevent neurite outgrowth (19)(20)(21). After the effects of these molecules have been blocked by a specific monoclonal antibody (IN-1) neurons can once again grow across spinal cord lesions at stages when regeneration would normally be impossible (17,22,23). Thus, in r...

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REPAIR AND RECOVERY FOLLOWING SPINAL CORD INJURY IN A NEONATAL MARSUPIAL (MONODELPHIS DOMESTICA)

Cited by 49 publications

References 25 publications

Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes

Pediatric Spinal Cord Injury in Infant Piglets: Description of a New Large Animal Model and Review of the Literature

Myelin-associated neurite growth-inhibitory proteins and suppression of regeneration of immature mammalian spinal cord in culture.

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