Modulating astrogliosis after neurotrauma

McGraw, John J.; Hiebert, Gordon W.; Steeves, John D.

doi:10.1002/1097-4547(20010115)63:2<109::aid-jnr1002>3.0.co;2-j

Cited by 256 publications

(143 citation statements)

References 64 publications

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“…Experimental models developed to simulate the compression type of acute cord trauma include the weight-dropping technique (Allen, 1911;Basso et al, 1995Basso et al, , 1996, extradural inflatable balloon compression (Tarlov et al, 1953), and aneurysm clip compression (Rivlin and Tator, 1978;Fehlings and Tator, 1995). After contusion or compression trauma to the spinal cord, sequential pathological changes including hemorrhage, edema, axonal and neuronal necrosis, and demyelination followed by cystic formation are described in the lesion site (Schwab and Bartholdi, 1996;Taoka and Okajima, 1998;McGraw et al, 2001). Between 15 and 30 min posttrauma, small hemorrhages with extravasation of erythrocytes and plasma into the perivascular spaces were seen.…”

Section: Discussionmentioning

confidence: 99%

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

Verdú

García-Alías

Forés

et al. 2003

Glia

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We studied the effects of olfactory ensheathing cells (OECs) transplanted in a photochemical spinal cord injury in adult rats. After dorsal laminectomy at T8 vertebra, subjacent spinal cord was bathed with rose Bengal for 10 min and illuminated with visible light by means of an optic fiber connected to a halogen lamp for 2.5 min at maximal intensity of 8 kLux. Eight injured rats received a suspension of OECs in DMEM, and another eight rats received DMEM alone. Locomotor ability scored by the BBB scale, pain sensibility by the plantar algesimetry test, and motor-and somatosensory-evoked potentials by electrophysiological techniques were evaluated for 3 months postsurgery. Finally, all rats were perfused with paraformaldehyde and transverse sections from the spinal cord segment at the lesion site were immunostained against GFAP. Area of the preserved spinal cord parenchyma was measured from the GFAPimmunolabeled cord sections. The BBB score and the amplitude of motor-and somatosensory-evoked potentials were higher in OECs-transplanted rats than in DMEMinjected animals throughout follow-up, whereas the withdrawal response to heat noxious stimulus was lower in OEC-than in DMEM-injected rats. The area of preserved spinal cord was significantly larger in OECs-transplanted rats than in DMEM-injected animals. These results indicate that OECs promote functional and morphological preservation of the spinal cord after photochemical injury. GLIA 42:275-286, 2003.

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Section: Discussionmentioning

confidence: 99%

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

Verdú

García-Alías

Forés

et al. 2003

Glia

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“…Traditionally, thought to be a simple mechanical barrier (Windle and Chambers, 1950), later studies suggested that regeneration still fails even when a dense glial scar does not form (Guth et al, 1986). Multiple models have now demonstrated that the molecular composition of the scar and the production of inhibitory molecules by astrocytes are contributing factors for regenerative failure (Busch and Silver, 2007;Fawcett, 2006;Fitch and Silver, 1997a;Fitch and Silver, 2000;Liu et al, 2006;McGraw et al, 2001;Silver and Miller, 2004;Yiu and He, 2006;Zhang et al, 2006). Reactive astrocytes within the glial scar have been shown to upregulate molecules such as tenascin (Apostolova et al, 2006;Brodkey et al, 1995;McKeon et al, 1995), Semaphorin 3 (Pasterkamp et al, 2001), ephrin-B2 (Bundesen et al, 2003), slit proteins (Hagino et al, 2003), and a host of chondroitin sulfate proteoglycans (Jones et al, 2003a;McKeon, et al, 1995;Rhodes and Fawcett, 2004).…”

Section: Molecules Within the Glial Scar Contribute To Regenerative Fmentioning

confidence: 99%

CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regeneration failure

Fitch

Silver

2008

Experimental Neurology

877

657

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Spinal cord and brain injuries lead to complex cellular and molecular interactions within the central nervous system in an attempt to repair the initial tissue damage. Many studies have illustrated the importance of the glial cell response to injury, and the influences of inflammation and wound healing processes on the overall morbidity and permanent disability that result. The abortive attempts of neuronal regeneration after spinal cord injury are influenced by inflammatory cell activation, reactive astrogliosis and the production of both growth promoting and inhibitory extracellular molecules. Despite the historical perspective that the glial scar was a mechanical barrier to regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Unlike myelin associated inhibitory molecules, which remain at largely static levels before and after central nervous system trauma, inhibitory extracellular matrix molecules are dramatically upregulated during the inflammatory stages after injury providing a window of opportunity for the delivery of candidate therapeutic interventions. While high dose methylprednisolone steroid therapy alone has not proved to be the solution to this difficult clinical problem, other strategies for modulating inflammation and changing the make up of inhibitory molecules in the extracellular matrix are providing robust evidence that rehabilitation after spinal cord and brain injury has the potential to significantly change the outcome for what was once thought to be permanent disability.

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“…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%