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Advances in Pharmacological Sciences
Volume 2012 (2012), Article ID 708428, 8 pages
Review Article

Perisynaptic GABA Receptors: The Overzealous Protector

Departments of Anatomy and Psychology, University of Otago, P.O. Box 913, Dunedin 9013, New Zealand

Received 13 April 2011; Accepted 12 December 2011

Academic Editor: John Atack

Copyright © 2012 Andrew N. Clarkson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


An attempt to find pharmacological therapies to treat stroke patients and minimize the extent of cell death has seen the failure of dozens of clinical trials. As a result, stroke/cerebral ischemia is the leading cause of lasting adult disability. Stroke-induced cell death occurs due to an excess release of glutamate. As a consequence to this, a compensatory increased release of GABA occurs that results in the subsequent internalization of synaptic GABAA receptors and spillover onto perisynaptic GABAA receptors, resulting in increased tonic inhibition. Recent studies show that the brain can engage in a limited process of neural repair after stroke. Changes in cortical sensory and motor maps and alterations in axonal structure are dependent on patterned neuronal activity. It has been assumed that changes in neuronal excitability underlie processes of neural repair and remapping of cortical sensory and motor representations. Indeed, recent evidence suggests that local inhibitory and excitatory currents are altered after stroke and modulation of these networks to enhance excitability during the repair phase can facilitate functional recovery after stroke. More specifically, dampening tonic GABA inhibition can afford an early and robust improvement in functional recovery after stroke.