Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats.

Abstract

Stroke is the dominant cause of sensorimotor disability that primarily affects the elderly. We now show that neuroplasticity and functional recovery after stroke is constrained by inhibitory chondroitin sulphates. In two blinded, randomized preclinical trials, degradation of chondroitin sulphate using chondroitinase ABC reactivated neuroplasticity and promoted sensorimotor recovery after stroke in elderly rats. Three days after stroke, chondroitinase ABC was microinjected into the cervical spinal cord to induce localized plasticity of forelimb sensorimotor spinal circuitry. Chondroitinase ABC effectively removed chondroitin sulphate from the extracellular matrix and perineuronal nets. Three different tests of sensorimotor function showed that chondroitinase ABC promoted recovery of forelimb function. Anterograde and retrograde tracing showed that chondroitinase ABC also induced sprouting of the contralesional corticospinal tract in the aged treated hemicord. Chondroitinase ABC did not neuroprotect the peri-infarct region. We show for the first time delayed chondroitinase ABC treatment promotes neuroanatomical and functional recovery after focal ischaemic stroke in an elderly nervous system.

• Authors: Sara Soleman, Ping K Yip, Denise A Duricki, Lawrence D F Moon
• Journal: Brain : a journal of neurology (Brain) Vol. 135 Issue Pt 4 Pg. 1210-23 (Apr 2012) ISSN: 1460-2156 [Electronic] England
• PMID: 22396394 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amidines
• Chondroitin Sulfate Proteoglycans
• Dextrans
• Plant Lectins
• Receptors, N-Acetylglucosamine
• biotinylated dextran amine
• diamidino compound 253-50
• wisteria lectin
• Biotin
• Chondroitin ABC Lyase

Topics

• Acoustic Stimulation (adverse effects)
• Aging
• Amidines
• Analysis of Variance
• Animals
• Biotin (analogs & derivatives, metabolism)
• Brain Infarction (drug therapy, etiology)
• Chondroitin ABC Lyase (administration & dosage)
• Chondroitin Sulfate Proteoglycans (metabolism)
• Dextrans (metabolism)
• Disease Models, Animal
• Double-Blind Method
• Female
• Forelimb (physiopathology)
• Functional Laterality (drug effects)
• Gait Disorders, Neurologic (drug therapy, etiology)
• Injections, Spinal (methods)
• Male
• Movement Disorders (etiology)
• Neuronal Plasticity (drug effects)
• Neurons (drug effects, metabolism)
• Plant Lectins
• Psychomotor Performance (drug effects)
• Pyramidal Tracts (pathology)
• Rats
• Rats, Long-Evans
• Receptors, N-Acetylglucosamine
• Recovery of Function (drug effects)
• Sensation Disorders (etiology)
• Stroke (complications, drug therapy, pathology)
• Time Factors