The Experts below are selected from a list of 29151 Experts worldwide ranked by ideXlab platform
James W. Fawcett - One of the best experts on this subject based on the ideXlab platform.
-
Overcoming inhibition in the damaged spinal cord.
Journal of neurotrauma, 2006Co-Authors: James W. FawcettAbstract:Inhibition by several inhibitory molecules on oligodendrocytes, and by chondroitin sulphate proteoglycans and semaphorins in the glial scar discourages Regeneration of axons in the injured spinal cord. This inhibition is compounded by the poor regenerative ability of most central nervous system (CNS) axons. Treatments that block some of these inhibitory mechanisms Promote Regeneration in animal models of cord injury. Plasticity is also reduced by some of the inhibitory molecules, and some of the treatments that Promote Regeneration also Promote plasticity. This is probably a more achievable therapeutic target than axon Regeneration, and an effective treatment would be of assistance to the majority of patients with partial cord injuries.
-
building a bridge engineering spinal cord repair
Experimental Neurology, 2002Co-Authors: Herbert M Geller, James W. FawcettAbstract:Injuries to the spinal cord that result in disruption of axonal continuity have devastating consequences for injured patients. Current therapies that use biologically active agents to Promote neuronal survival and/or growth have had modest success in allowing injured neurons to regrow through the area of the lesion. Strategies for successful Regeneration will require an engineering approach. We propose the design of cell-free grafts of biocompatible materials to build a bridge across the injured area through which axons can regenerate. There are three critical regions of this bridge: the on-ramp, the surface of the bridge itself, and the off-ramp. Each of these regions has specific design requirements, which, if met, can Promote Regeneration of axons in the injured spinal cord. These requirements, and proposed solutions, are discussed.
Jane A Roskams - One of the best experts on this subject based on the ideXlab platform.
-
peripheral olfactory ensheathing cells reduce scar and cavity formation and Promote Regeneration after spinal cord injury
The Journal of Comparative Neurology, 2004Co-Authors: Leanne M Ramer, Miranda W Richter, Jie Liu, Wolfram Tetzlaff, Jane A RoskamsAbstract:International Collaboration on Repair Discoveries, University of British Columbia,Vancouver, British Columbia V6T 1Z4, CanadaABSTRACTBridging of a lesion site and minimizing local damage to create an environment permis-sive for Regeneration are both primary components of a successful strategy to repair spinalcord injury (SCI). Olfactory ensheathing cells (OECs) are prime candidates for autologoustransplantation to bridge this gap, but little is known currently about their mechanism ofaction. In addition, OECs from the accessible lamina propria (LP) of the olfactory mucosa area more viable source in humans but have yet to be tested for their ability to PromoteRegeneration in established SCI models. Here, mouse LP-OECs expressing green fluorescentprotein (GFP) transplanted directly into both rat and mouse dorsolateral spinal cord lesionsites demonstrate limited migration but interact with host astrocytes to develop a newtransitional zone at the lesion border. LP-OECs also Promote extensive migration of hostSchwann cells into the central nervous system repair zone and stimulate angiogenesis toprovide a biological scaffold for repair. This novel environment created by transplanted andhost glia within the spinal cord inhibits cavity and scar formation and Promotes extensivesprouting of multiple sensory and motor axons into and through the lesion site. Sixty daysafter rat SCI, serotonin- and tyrosine hydroxylase-positive axons sprouted across the lesioninto the distal cord, although axotomized rubrospinal axons did not. Thus, even in a xeno-transplant paradigm, LP-OECs work collaboratively with host glial cells to create an envi-ronment to ameliorate local damage and simultaneously Promote a regenerative response inmultiple axonal populations. J. Comp. Neurol. 473:1–15, 2004.
-
olfactory ensheathing cells of the lamina propria in vivo and in vitro
Glia, 2003Co-Authors: Edmund Au, Jane A RoskamsAbstract:Olfactory ensheathing cells (OECs) continuously support the regener- ation of olfactory receptor neurons (ORNs). In addition, OECs Promote Regeneration of neurons within the CNS in a number of transplantation paradigms, but details of exactly how they support Regeneration remain elusive. The majority of studies using OECs to Promote Regeneration have thus far focused on understanding the cell biology of OECs purified from the olfactory bulb (OB). Here we show that a population of OECs similar to those obtained from the OB is present in the lamina propria (LP) beneath the olfactory epithelium (OE). These OECs are the first glial cells encountered by the axons of developing ORNs as they exit the OE and display distinct and variable expression of p75, S100! , GFAP, and O4, characteristic markers of bulb OECs. Once purified in vitro, they display Schwann cell-like and astrocyte-like properties and expand rapidly. In addition to resembling OB-OECs, LP-OECs also express a unique combination of devel- opmentally important proteins—CD 44, ! 1 integrin, P200, Notch 3, NG2, VEGF, and PACAP and CREB binding protein (CBP/p300)—not previously reported in OB-OECs. These data suggest that LP-OECs, like OB-OECs, are a developmentally distinct class of glia that are capable of both immature and mature function, depending on environ- mental stimuli, within the adult nervous system. GLIA 41:224-236, 2003. © 2003 Wiley-Liss, Inc.
Juan Larraín - One of the best experts on this subject based on the ideXlab platform.
-
Spinal cord Regeneration: lessons for mammals from non-mammalian vertebrates.
genesis, 2013Co-Authors: Dasfne Lee-liu, Gabriela Edwards-faret, Victor S. Tapia, Juan LarraínAbstract:Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord Regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal Regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative-permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for Regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow Regeneration. This comparison should lead us toward finding how to Promote Regeneration in organisms that are unable to do so.
Herbert M Geller - One of the best experts on this subject based on the ideXlab platform.
-
An In Vitro Model of Reactive Astrogliosis and Its Effect on Neuronal Growth
Methods in molecular biology (Clifton N.J.), 2011Co-Authors: Hang Wang, Yasuhiro Katagiri, Herbert M GellerAbstract:Astrogliosis, whereby astrocytes in the central nervous system (CNS) become reactive in response to tissue damage, is a prominent process leading to the formation of the glial scar that inhibits axon Regeneration after CNS injury. Upon becoming reactive, astrocytes undergo various molecular and morphological changes including upregulating their expression of GFAP and chondroitin sulfate proteoglycans (CSPGs) as well as other molecules that are inhibitory to axon growth. We have developed an in vitro model of reactive astrogliosis as a result of treating cultured astrocytes with transforming growth factor-β (TGF-β), which induces increased expression as well as secretion of CSPGs. These reactive astrocytes show inhibitory effects on neuron growth both in neuron-astrocyte coculture and in neurite guidance spot assay using astrocyte-conditioned medium. These reactive astrocytes provide a vehicle for testing substances that might overcome the glial scar and Promote Regeneration.
-
building a bridge engineering spinal cord repair
Experimental Neurology, 2002Co-Authors: Herbert M Geller, James W. FawcettAbstract:Injuries to the spinal cord that result in disruption of axonal continuity have devastating consequences for injured patients. Current therapies that use biologically active agents to Promote neuronal survival and/or growth have had modest success in allowing injured neurons to regrow through the area of the lesion. Strategies for successful Regeneration will require an engineering approach. We propose the design of cell-free grafts of biocompatible materials to build a bridge across the injured area through which axons can regenerate. There are three critical regions of this bridge: the on-ramp, the surface of the bridge itself, and the off-ramp. Each of these regions has specific design requirements, which, if met, can Promote Regeneration of axons in the injured spinal cord. These requirements, and proposed solutions, are discussed.
Mary Bartlett Bunge - One of the best experts on this subject based on the ideXlab platform.
-
Olfactory Ensheathing Glia: Their Application to Spinal Cord Regeneration and Remyelination Strategies
Topics in Spinal Cord Injury Rehabilitation, 2000Co-Authors: Naomi Kleitman, Mary Bartlett BungeAbstract:Grafts of peripheral nerves or peripheral nervous system (PNS) Schwann cells were among the first successful strategies applied to Promote Regeneration in the central nervous system (CNS). However, glial cells of the PNS and CNS (Schwann cells and astrocytes, respectively) establish borders where they meet, preventing functional reconnection between regenerating axons and CNS targets. Olfactory ensheathing glia (OEG) are cells that share characteristics with both Schwann cells and astrocytes and support the growth of olfactory nerve axons into the CNS throughout life. Application of these cells to Promote Regeneration and remyelination in the spinal cord is reviewed.
-
the ability of human schwann cell grafts to Promote Regeneration in the transected nude rat spinal cord
Experimental Neurology, 1997Co-Authors: James D Guest, Mary Bartlett Bunge, Arundathi Rao, Les Olson, Richard P BungeAbstract:Abstract Advances in the purification and expansion of Schwann cells (SCs) from adult human peripheral nerve, together with biomaterials development, have made the construction of unique grafts with defined properties possible. We have utilized PAN/PVC guidance channels to form solid human SC grafts which can be transplanted either with or without the channel. We studied the ability of grafts placed with and without channels to support Regeneration and to influence functional recovery; characteristics of the graft and host/graft interface were also compared. The T9–T10 spinal cord of nude rats was resected and a graft was placed across the gap; methylprednisolone was delivered acutely to decrease secondary injury. Channels minimized the immigration of connective tissue into grafts but contributed to some necrotic tissue loss, especially in the distal spinal cord. Grafts without channels contained more myelinated axons (x= 2129 ± 785) vs (x = 1442 ± 514) and were larger in cross-sectional area (x = 1.53 ± 0.24 mm2) vs (x= 0.95 ± 0.86 mm2). The interfaces formed between the host spinal cord and the grafts placed without channels were highly interdigitated and resembled CNS–PNS transition zones; chondroitin sulfate proteoglycans was deposited there. Whereas several neuronal populations including propriospinal, sensory, motoneuronal, and brainstem neurons regenerated into human SC grafts, only propriospinal and sensory neurons were observed to reenter the host spinal cord. Using combinations of anterograde and retrograde tracers, we observed Regeneration of propriospinal neurons up to 2.6 mm beyond grafts. We estimate that 1% of the fibers that enter grafts reenter the host spinal cord by 45 days after grafting. Following retrograde tracing from the distal spinal cord, more labeled neurons were unexpectedly found in the region of the dextran amine anterograde tracer injection site where a marked inflammatory reaction had occurred. Animals with bridging grafts obtained modestly higher scores during open field [(x = 8.2 ± 0.35) vs (x = 6.8 ± 0.42),P = 0.02] and inclined plane testing (x = 38.6 ± 0.542) vs (x= 36.3 ± 0.53),P = 0.006] than animals with similar grafts in distally capped channels. In summary, this study showed that in the nude rat given methylprednisolone in combination with human SC grafts, some regenerative growth occurred beyond the graft and a modest improvement in function was observed.
