Compartment- and context-specific changes in tissue-type plasminogen activator (tPA) activity following brain injury and pharmacological stimulation

M Sashindranath; AL Samson; CE Downes; PJ Crack; AJ Lawrence; QX Li; AQP Ng; NC Jones; JJ Farrugia; E Abdella; JD Vassalli; R Madani; RL Medcalf

Journal article

Compartment- and context-specific changes in tissue-type plasminogen activator (tPA) activity following brain injury and pharmacological stimulation

M Sashindranath, AL Samson, CE Downes, PJ Crack, AJ Lawrence, QX Li, AQP Ng, NC Jones, JJ Farrugia, E Abdella, JD Vassalli, R Madani, RL Medcalf

Laboratory Investigation | NATURE PUBLISHING GROUP | Published : 2011

DOI: 10.1038/labinvest.2011.67

Abstract

Tissue-type plasminogen activator (tPA) is a major protease of the central nervous system. Most studies to date have used in situ- or gel-based zymographic assays to monitor in vivo changes in neural tPA activity. In this study, we demonstrate that the amidolytic assay can be adapted to accurately detect changes in net tPA activity in mouse brain tissues. Using the amidolytic assay, we examined differences in net tPA activity in the cerebral cortex, sub-cortical structures and cerebellum in wildtype (WT) and tPA / mice, and in transgenic mice selectively overexpressing tPA in neurons. In addition, we assessed changes in endogenous net tPA activity in WT mice following morphine administration..

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University of Melbourne Researchers

Andre Samson Author

Peter Crack Author

Andrew Lawrence Author

Qiao-Xin Li Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank Prof Norman Saunders, Dr Mark Habgood, Dr Simone Beckham and Mr Adam Galle for constructing the electromagnetic CCI device. We also thank Ms Amanda Au for assisting in the preparation of mouse brain lysates following MCAo. Be'eri Niego for constructive comments regarding the amidolytic assay. Volga Tarlac and Elsdon Storey from the Van Cleef Roet Centre for Nervous Diseases for providing us with the SCA1 mutant and wild-type littermate mice, and Prof John Hamilton (Department of Medicine, Royal Melbourne Hospital) for providing the mice for the seizure studies. This study was supported by grant numbers 606659 awarded to RLM and ALS from the National Health and Medical Research Council (NH&MRC) of Australia and by grant numbers 491152 and 606660 awarded to RLM from the NH&MRC and D0-34 awarded to RLM from the Victorian Neurotrauma Initiative. This study was also supported by grant numbers 628391 and G 08M 3821 awarded to PJC from the NH&MRC and the National Heart Foundation of Australia, respectively, and by grant number 566544 awarded to NCJ from the NH&MRC. AJL and RLM are also supported with Senior Research Fellowships, and NCJ supported with a Career Development Award, from the NH&MRC.