Benefit of chondroitinase ABC on sensory axon regeneration in a laceration model of spinal cord injury in the rat

Shields, Lisa B. E.; Zhang, Yi Ping; Burke, Darlene A.; Gray, Rebecca N; Shields, Christopher B.

doi:10.1016/j.surneu.2008.02.009

Cited by 48 publications

(32 citation statements)

References 62 publications

(81 reference statements)

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“…So far, few studies have addressed the impact of ChABC treatment on astrocyte morphology, and none reported any relevant influence on scar formation, 57,58 excepting the work of Chau and colleagues, 59 who combined ChABC treatment with Schwann cell grafts, which resulted in a decrease of GFAP labeling and stimulation of astrocytic processes entering the graft tissue. Our present study clearly demonstrates that treating the injured spinal cord with ChABC alone was sufficient to achieve the modification of the astrocytic reaction described by Chau and colleagues.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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Upregulation of extracellular chondroitin sulfate proteoglycans (CSPG) is a primary cause for the failure of axons to regenerate after spinal cord injury (SCI), and the beneficial effect of their degradation by chondroitinase ABC (ChABC) is widely documented. Little is known, however, about the effect of ChABC treatment on astrogliosis and revascularization, two important factors influencing axon regrowth. This was investigated in the present study. Immediately after a spinal cord hemisection at thoracic level 8-9, we injected ChABC intrathecally at the sacral level, repeated three times until 10 days post-injury. Our results show an effective cleavage of CSPG glycosaminoglycan chains and stimulation of axonal remodeling within the injury site, accompanied by an extended period of astrocyte remodeling (up to 4 weeks). Interestingly, ChABC treatment favored an orientation of astrocytic processes directed toward the injury, in close association with axons at the lesion entry zone, suggesting a correlation between axon and astrocyte remodeling. Further, during the first weeks post-injury, ChABC treatment affected the morphology of laminin-positive blood vessel basement membranes and vessel-independent laminin deposits: hypertrophied blood vessels with detached or duplicated basement membrane were more numerous than in lesioned untreated animals. In contrast, at later time points, laminin expression increased and became more directly associated with newly formed blood vessels, the size of which tended to be closer to that found in intact tissue. Our data reinforce the idea that ChABC injection in combination with other synergistic treatments is a promising therapeutic strategy for SCI repair.

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Section: Discussionmentioning

confidence: 99%

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Milbreta

Boxberg

Mailly

et al. 2014

Journal of Neurotrauma

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“…When applied to an acute cervical dorsal column crush lesion, ChaseABC enhances axonal regeneration and locomotor and proprioceptive recovery in these animals, demonstrating that in vivo ChaseABC delivery can lead to anatomical and functional recovery (Bradbury et al, 2002). Regeneration of sensory axons and also axons in Clarke's nucleus after hemisection injury was also observed following ChaseABC treatment (Yick et al, 2003;Shields et al, 2008). Acute and delayed intrathecal ChaseABC infusion to a rubospinal tract lesion reduced the atrophy of neuronal cell bodies of the rubospinal neurons, suggesting a neuroprotective role for ChaseABC (Carter et al, 2011).…”

Section: Ecm and Pnns In Cns Injuriesmentioning

confidence: 92%

Extracellular matrix and perineuronal nets in CNS repair

Kwok

Dick

Wang

et al. 2011

Developmental Neurobiology

354

304

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A perineuronal net (PNN) is a layer of lattice-like matrix which enwraps the surface of the soma and dendrites, and in some cases the axon initial segments, in sub-populations of neurons in the central nervous system (CNS). First reported by Camillo Golgi more than a century ago, the molecular structure and the potential role of this matrix have only been unraveled in the last few decades. PNNs are mainly composed of hyaluronan, chondroitin sulfate proteoglycans, link proteins, and tenascin R. The interactions between these molecules allow the formation of a stable pericellular complex surrounding synapses on the neuronal surface. PNNs appear late in development co-incident with the closure of critical periods for plasticity. They play a direct role in the control of CNS plasticity, and their removal is one way in which plasticity can be re-activated in the adult CNS. In this review, we examine the molecular components and formation of PNNs, their role in maturation and synaptic plasticity after CNS injury, and the possible mechanisms of PNN action.

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“…In keeping with the interest in ChABC's putative mechanism of action, 13 of the 24 studies were solely focused on anatomical=histologic outcomes, with no measurement of behavioral outcome (Carter et al, 2008;Chau et al, 2004;Fouad et al, 2009;Iaci et al, 2007;Ikegami et al, 2005;Iseda et al, 2008;Massey et al, 2006Massey et al, , 2008Shields et al, 2008;Tan et al, 2006;Tom and Houlé, 2008;Vavrek et al, 2007;Xia et al, 2008;Yick et al, 2003). In general, independent laboratories report ChABC promoting increased axonal sprouting (particularly serotonergic fibers) using either anterograde or retrograde tracing techniques.…”

Section: Chondroitinase Abcmentioning

confidence: 99%

“…In general, independent laboratories report ChABC promoting increased axonal sprouting (particularly serotonergic fibers) using either anterograde or retrograde tracing techniques. As an adjunct treatment to a transplantation therapy (e.g., Schwann cells, peripheral nerve graft), ChABC reportedly improved axonal growth and=or serotonergic sprouting (Chau et al, 2004;Fouad et al, 2005;Houle et al, 2006;Shields et al, 2008;Tom and Houlé, 2008). Xia and colleagues (2008) reported a reduced cystic cavity, suggestive of some neuroprotective effect.…”

Section: Chondroitinase Abcmentioning

confidence: 99%

A Systematic Review of Directly Applied Biologic Therapies for Acute Spinal Cord Injury

Kwon

Okon

Plunet

et al. 2011

Journal of Neurotrauma

108

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An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically reviewed the available preclinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we reviewed treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications or are available in a form that could be administered to humans. These included: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in vivo animal model was utilized to assess the efficacy of the therapy in a traumatic spinal cord injury paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the preclinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.

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Benefit of chondroitinase ABC on sensory axon regeneration in a laceration model of spinal cord injury in the rat

Cited by 48 publications

References 62 publications

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Astrocytic and Vascular Remodeling in the Injured Adult Rat Spinal Cord after Chondroitinase ABC Treatment

Extracellular matrix and perineuronal nets in CNS repair

A Systematic Review of Directly Applied Biologic Therapies for Acute Spinal Cord Injury

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