Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London, UK.
Brain. 2012 Apr;135(Pt 4):1210-23. doi: 10.1093/brain/aws027. Epub 2012 Mar 6.
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.
中风是导致感觉运动障碍的主要原因，主要影响老年人。我们现在表明，中风后的神经可塑性和功能恢复受到抑制性硫酸软骨素的限制。在两项盲法、随机的临床前试验中，使用软骨素酶 ABC 降解硫酸软骨素可重新激活神经可塑性，并促进老年大鼠中风后的感觉运动恢复。中风后 3 天，将软骨素酶 ABC 微注射到颈脊髓中，以诱导前肢感觉运动脊髓回路的局部可塑性。软骨素酶 ABC 可有效从细胞外基质和神经周网中去除硫酸软骨素。三种不同的感觉运动功能测试表明，软骨素酶 ABC 促进了前肢功能的恢复。顺行和逆行示踪显示，软骨素酶 ABC 还诱导了治疗半脊髓中对侧皮质脊髓束的发芽。软骨素酶 ABC 没有保护梗死周围区域免受神经损伤。我们首次表明，延迟的软骨素酶 ABC 治疗可促进老年神经系统局灶性缺血性中风后的神经解剖和功能恢复。
