Muscle-specific kinase myasthenia gravis IgG4 autoantibodies cause severe neuromuscular junction dysfunction in mice
Open Access
- 6 March 2012
- journal article
- Published by Oxford University Press (OUP) in Brain
- Vol. 135 (4), 1081-1101
- https://doi.org/10.1093/brain/aws025
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.Keywords
This publication has 72 references indexed in Scilit:
- Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in miceThe Journal of Physiology, 2010
- Immunoglobulin G4: an odd antibodyClinical and Experimental Allergy, 2009
- Anti‐MuSK patient antibodies disrupt the mouse neuromuscular junctionAnnals of Neurology, 2008
- MuSK is required for anchoring acetylcholinesterase at the neuromuscular junctionThe Journal of cell biology, 2004
- Synaptic gain control and homeostasisCurrent Opinion in Neurobiology, 2003
- Maintaining the Stability of Neural Function: A Homeostatic HypothesisAnnual Review of Physiology, 2001
- Spontaneous Electromyographic Activity in Adult Rat Soleus MuscleJournal of Neurophysiology, 1998
- Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complexNeuron, 1995
- Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies.The Journal of Experimental Medicine, 1987
- On the release of transmitter at normal, myasthenia gravis and myasthenic syndrome affected human end‐plates.The Journal of Physiology, 1980