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Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury

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Abstract

Unveiling the mechanisms participating in the damage and repair of traumatic brain injury (TBI) is fundamental to develop new therapies. The P2Y-like GPR17 receptor has recently emerged as a sensor of damage and a key actor in lesion remodeling/repair in the rodent brain, but its role in humans is totally unknown. Here, we characterized GPR17 expression in brain specimens from seven intensive care unit TBI patients undergoing neurosurgery for contusion removal and from 28 autoptic TBI cases (and 10 control subjects of matched age and gender) of two university hospitals. In both neurosurgery and autoptic samples, GPR17 expression was strong inside the contused core and progressively declined distally according to a spatio-temporal gradient. Inside and around the core, GPR17 labeled dying neurons, reactive astrocytes, and activated microglia/macrophages. In peri-contused parenchyma, GPR17 decorated oligodendrocyte precursor cells (OPCs) some of which had proliferated, indicating re-myelination attempts. In autoptic cases, GPR17 expression positively correlated with death for intracranial complications and negatively correlated with patients’ post-traumatic survival. Data indicate lesion-specific sequential involvement of GPR17 in the (a) death of irreversibly damaged neurons, (b) activation of microglia/macrophages remodeling the lesion, and (c) activation/proliferation of multipotent parenchymal progenitors (both reactive astrocytes and OPCs) starting repair processes. Data validate GPR17 as a target for neurorepair and are particularly relevant to setting up new therapies for TBI patients.

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Acknowledgments

The authors thank Prof. Enzo Wanke, University of Bicocca-Milan and Dr. Annalisa Buffo, University of Turin for useful discussion. The authors are also grateful to Prof. J. Dreßler and Benjamin Ondruschka (Institute for Legal Medicine, Medical Faculty University of Leipzig) for providing autoptic samples, to Dr. Mauro Pluderi, MD, and Dr. Marco Locatelli, MD, from the Department of Neurosurgery of the Ospedale Maggiore Policlinico di Milano for assistance in resection of contusions and collection of neurosurgical brain samples, and to Mrs. Katrin Becker (RBI of Pharmacology and Toxicology, Leipzig) for expert technical assistance. This work was partially supported by the Italian PRIN-COFIN (Project Prot. 2006059022 and 2008XFMEA3 to M.P.A) and by Deutsche Forschungsgemeinschaft (FR 1253/3-2); C.P. was supported by a Fondazione Cariplo fellowship (project number 2008.2907); M.F. is supported by a fellowship from Fondazione Italiana Sclerosi Multipla (grant N. 2010/R/2); C.H. was supported by a funding from the German Federal Ministry of Education and Research (BMBF, PtJ-Bio, 0313909), the European Fund for Regional Development (EFRE), and the Free State of Saxony (grant no. SAB12525).

Conflict of interest

None declared.

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Authors and Affiliations

  1. Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany

    Heike Franke, Claudia Heine & Kristina Bremicker

  2. Department of Pharmacological and Biomolecular Sciences, Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, University of Milan, via Balzaretti 9, 20133, Milan, Italy

    Chiara Parravicini, Davide Lecca, Marta Fumagalli & Maria P. Abbracchio

  3. IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy

    Elisa R. Zanier & Maria-Grazia De Simoni

  4. Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany

    Claudia Heine

  5. Department of Medical Pharmacology, Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Milan, Italy

    Patrizia Rosa

  6. Department of Pathophysiology and Transplantation, University of Milan, and Neurosurgical Care Unit, IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy

    Luca Longhi & Nino Stocchetti

  7. Institute of Legal Medicine, University of Halle, Halle (Saale), Germany

    Marco Weber

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  1. Heike Franke
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  2. Chiara Parravicini
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  13. Maria P. Abbracchio
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Corresponding author

Correspondence to Maria P. Abbracchio.

Additional information

Heike Franke, Chiara Parravicini, and Davide Lecca have contributed equally to this study.

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Franke, H., Parravicini, C., Lecca, D. et al. Changes of the GPR17 receptor, a new target for neurorepair, in neurons and glial cells in patients with traumatic brain injury. Purinergic Signalling 9, 451–462 (2013). https://doi.org/10.1007/s11302-013-9366-3

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  • DOI: https://doi.org/10.1007/s11302-013-9366-3

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