Chondroitinase Combined with Rehabilitation Promotes Recovery of Forelimb Function in Rats with Chronic Spinal Cord Injury

Abstract

Chondroitinase ABC (ChABC) in combination with rehabilitation has been shown to promote functional recovery in acute spinal cord injury. For clinical use, the optimal treatment window is concurrent with the beginning of rehabilitation, usually 2-4 weeks after injury. We show that ChABC is effective when given 4 weeks after injury combined with rehabilitation. After C4 dorsal spinal cord injury, rats received no treatment for 4 weeks. They then received either ChABC or penicillinase control treatment followed by hour-long daily rehabilitation specific for skilled paw reaching. Animals that received both ChABC and task-specific rehabilitation showed the greatest recovery in skilled paw reaching, approaching similar levels to animals that were treated at the time of injury. There was also a modest increase in skilled paw reaching ability in animals receiving task-specific rehabilitation alone. Animals treated with ChABC and taskspecific rehabilitation also showed improvement in ladder and beam walking. ChABC increased sprouting of the corticospinal tract, and these sprouts had more vGlut1 ϩve presynaptic boutons than controls. Animals that received rehabilitation showed an increase in perineuronal net number and staining intensity. Our results indicate that ChABC treatment opens a window of opportunity in chronic spinal cord lesions, allowing rehabilitation to improve functional recovery.

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

“…it is therefore important to study the treatment effects of regenerative treatments in combination with rehabilitation. ChABC opens a window of plasticity and has proven effective when specific rehabilitation is given during the period of drug administration, in both acute and delayed stages and up to one year post-injury in two SCi models [16,31] .…”

“…ChABC has been shown in many in vitro and in vivo models to be an effective treatment for improving axonal regeneration and sprouting, and for promoting functional recovery in acute and chronic SCi in various animal models [13][14][15][16][17] . in animal experiments, ChABC treatment allows some axons to regenerate through the lesion, and leads to an increased sprouting response in both lesioned and spared systems after SCi [18] .…”

“…in animal experiments, ChABC treatment allows some axons to regenerate through the lesion, and leads to an increased sprouting response in both lesioned and spared systems after SCi [18] . ChABC also digests the PNNs [19] , and opens a window of plasticity which allows effective acquisition of motor skills with rehabilitation [12,16] .…”

Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury

“…Enzymatic digestion of the chondroitin sulfate side chains found on all CSPGs by intrathecal chondroitinase ABC treatment resulted in increased regeneration of ascending and descending tracts after SCI (Bradbury et al, 2002). The combination of chondroitinase ABC with peripheral nerve grafts (Alilain et al, 2011;Houle et al, 2006), rehabilitation (Garcia-Alias et al, 2009;Wang et al, 2011), or neural precursor cell transplantation (Karimi-Abdolrezaee et al, 2010) have all led to improved axonal regeneration and recovery.…”

Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains

“…Degradation of CS by enzymatic treatment using chondroitinase ABC (ChABC) has demonstrated remarkable enhancement in plasticity in the visual cortex (8) and in the injured CNS (11)(12)(13) and prolongation of memory (14). The same enhancement of plasticity and memory is also observed in animals that lack Crtl1 in the CNS and therefore have attenuated PNNs, indicating that ChABC promotes plasticity through digestion of CS-GAGs in PNNs (9).…”