Chondroitin Sulfate Proteoglycans in Spinal Cord Contusion Injury and the Effects of Chondroitinase Treatment

Abstract

Chondroitinase treatment of experimental spinal cord injury improves recovery of sensory, motor, and autonomic functions. Chondroitinase catalyzes the cleavage of glycosaminoglycans (GAGs) from the core proteins of chondroitin sulfate proteoglycans (CSPGs). Little is known about changes in production of these proteoglycans in the clinically relevant contusion model of spinal cord injury or if CSPG content is altered by chondroitinase treatment. Female Long-Evans rats were injured with a forceps contusion injury and treated on alternate days with chondroitinase ABCI or control enzyme via an intrathecal catheter. Spinal cords were analyzed at specific times after injury. The cord was divided in 4 mm long segments, one containing the lesion, two rostral and two caudal to the lesion. These segments were assessed for CSPG protein and message content (NG2, neurocan and phosphacan) by Western blotting and real-time PCR. CSPG protein content was increased by one day post injury for all CSPGs investigated, and was increased in all segments examined rostral and caudal to the lesion site. Significant increases in CSPG were observed with peak content detected at 7, 7 and 14 days post injury for NG2, neurocan and phosphacan, respectively. Chondroitinase treatment had little impact upon the CPSG protein content. Changes in message levels of these CSPGs are also reported. This demonstrates that expression patterns of CSPGs in contusion injury are similar to those surrounding surgical hemisection lesions and demonstrates that the sensory and motor function enhancing effects of chondroitinase are likely due to removal of GAG chains rather than reduction in CSPG content.

Plasticity After Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It

“…Furthermore, CSPGs produced by neurons and astrocytes form lattice-like perineuronal nets that shroud adult neuronal cell bodies and proximal dendrites [60,61]. Concentrations of some CSPGs increase in humans and animals not only at the SCI site [62][63][64][65][66][67][68][69][70][71] but also rostral [70] and caudal [72] to it.…”

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

“…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.…”

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC

“…However, injured axons are unable to regenerate across the site of injury in the central nervous system because of the presence of an array of inhibitory cues present within the scar (For a review, see 5,6), in particular chondroitin sulphate proteoglycans (CSPGs) (7)(8)(9)(10). Digestion of CSPGs with the bacterial enzyme chondroitinase ABC (ChABC), following local delivery to the spinal cord, has led to axon regeneration, plastic neuronal rearrangements and functional recovery following section or crush injury in laboratory animal SCI models (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Encouragingly, these findings have also been found using clinically relevant contusive injury rodent models (22,23) and large animal models such as cats and squirrel monkeys (19,24,25).…”