Chondroitinase ABC for neurological recovery after acute brain injury: systematic review and meta-analyses of preclinical studies

OBJECTIVES: Damage to critical brain regions causes deficits in important neurological functions. Chondroitinase ABC (ChABC) has been shown to promote neuroplasticity and may ameliorate neurological deficits caused by disease or trauma. This systematic review identifies and evaluates preclinical studies of ChABC as a treatment for acute brain injury.

METHODS: Four databases were searched for studies relating to ChABC and brain or brain injuries. Controlled studies in mammals with acute brain injuries treated with ChABC were included in meta-analyses of neurobehavioural outcomes. Means and standard deviations from the fifth day of treatment were extracted, and normalised mean differences were calculated.

RESULTS: Of 775 identified records, 16 studies administered ChABC after acute brain injury, of which 9 reported neurobehavioural outcomes. The estimated treatment effect on neurological recovery over the duration of included studies was 49.4% (CI: 30.3-68.4% with Hartung-Knapp-Sidik-Jonkman adjustment, p = 0.0002). The mechanisms of action may involve decreasing astroglial scar formation, promoting neuronal sprouting, and selective synaptic strengthening of sprouting neurites and activated neural pathways.

CONCLUSIONS: The summary of published evidence suggests that ChABC treatment is effective in improving neurological outcomes in preclinical models of acute brain injury. However, more studies are needed for better assessment of the specific translational potential of ChABC.

ABBREVIATIONS: AVM - Arteriovenous Malformation; ChABC - Chondroitinase ABC; CI - Confidence Interval; CSPG - Chondroitin Sulphate Proteoglycans; HKSJ - Hartung-Knapp-Sidik-Jonkman; MCA - Middle Cerebral Artery; NMD - Normalised Mean Difference; NSPC - Neural Stem/Progenitor Cells; PI - Prediction Interval; SD - Standard Deviation; SMD - Standardised Mean Difference; TBI - Traumatic Brain Injury.