The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke

• Type of Material: Article
• Authors: Valerie Jeanneret, Emory University; Manuel Yepes, Emory University
• Language: English
• Date: 2017-02
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Springer Science+Business Media New York 2016
• Final Published Version (URL): http://dx.doi.org/10.1007/s12975-016-0454-x
• Title of Journal or Parent Work: Translational Stroke Research
• ISSN: 1868-4483
• Volume: 8
• Issue: 1
• Start Page: 47
• End Page: 56
• Grant/Funding Information: This work has been supported in part by National Institutes of Health Grants NS-079331 (to MY) and NS-091201 (to MY).
• Keywords: Plasticity; Ischemic stroke; Urokinase-type plasminogen activator; Tissue-type plasminogen activator; Plasminogen activation; Recovery
• Research Categories: Biology, Neuroscience

Abstract

Advances in neurocritical care and interventional neuroradiology have led to a significant decrease in acute ischemic stroke (AIS) mortality. In contrast, due to the lack of an effective therapeutic strategy to promote neuronal recovery among AIS survivors, cerebral ischemia is still a leading cause of disability in the world. Ischemic stroke has a harmful impact on synaptic structure and function, and plasticity-mediated synaptic recovery is associated with neurological improvement following an AIS. Dendritic spines (DSs) are specialized dendritic protrusions that receive most of the excitatory input in the brain. The deleterious effect of cerebral ischemia on DSs morphology and function has been associated with impaired synaptic transmission and neurological deterioration. However, these changes are reversible if cerebral blood flow is restored on time, and this recovery has been associated with neurological improvement following an AIS. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are two serine proteases that besides catalyzing the conversion of plasminogen into plasmin in the intravascular and pericellular environment, respectively, are also are efficient inductors of synaptic plasticity. Accordingly, recent evidence indicates that both, tPA and uPA, protect DSs from the metabolic stress associated with the ischemic injury, and promote their morphological and functional recovery during the recovery phase from an AIS. Here we will review data indicating that plasticity-induced changes in DSs and the associated post-synaptic density play a pivotal role in the recovery process from AIS, making special emphasis on the role of tPA and uPA in this process.