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Blockade of P2 Nucleotide Receptors After Spinal Cord Injury Reduced the Gliotic Response and Spared Tissue

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Abstract

Spinal cord injury (SCI) triggers a sequel of events commonly associated with cell death and dysfunction of glias and neurons surrounding the lesion. Although astrogliosis and glial scar formation have been involved in both damage and repair processes after SCI, their role remains controversial. Our goal was to investigate the effects of the P2 receptors antagonists, PPADS and suramin, in the establishment of the reactive gliosis and the formation of the glial scar. Molecular biology, immunohistochemistry, spared tissue, and locomotor behavioral studies were used to evaluate astrogliosis, in adult female Sprague–Dawley rats treated with P2 antagonists after moderate injury with the NYU impactor device. Semi-quantitative RT-PCR confirmed the presence of P2Y1, P2Y2, P2Y4, P2Y6, P2Y12, and P2X2 receptors in the adult spinal cord. Immunohistochemistry studies confirmed a significant decrease in GFAP-labeled cells at the injury epicenter as well as a decrease in spared tissue after treatment with the antagonists. Functional open field testing revealed no significant locomotor score differences between treated and control animals. Our work is consistent with studies suggesting that astrogliosis is an important event after SCI that limits tissue damage and lesion spreading.

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Acknowledgements

The authors thank Luz C. Arocho and Laurivette Mosquera for the excellent technical assistance during surgeries and post-operatory procedures. Special thanks also to the personnel of the Animal Resources Center (University of Puerto Rico, Medical Science Campus) and the Experimental Surgery facilities. Our gratitude to Jose O. Garcia, Ph.D. for his critiques in the manuscript. This work was in partial fulfillment of Ana E. Rodríguez-Zayas doctoral dissertation and was supported by NIH-MRISP (2 R24 MH 48190–14), NIH-SNRP (NS39405), MBRS- SCORE (S06-GM008224), MBRS-RISE (GM-68138) and the Associated Deanship of Biomedical Sciences and Graduate Studies of the UPR School of Medicine. Editorial support was provided by Dr. Mary Helen Mays, Puerto Rico Clinical and Translational Research Consortium, funded by the National Center for Research Resources (NCRR) (1U54RR026139-01A1), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

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  1. Department of Physiology, University of Puerto Rico School of Medicine, Medical Science Campus, PO Box 365067, San Juan, PR, 00936-5067, Puerto Rico

    Ana E. Rodríguez-Zayas, Aranza I. Torrado, Odrick R. Rosas, José M. Santiago & Jorge D. Miranda

  2. Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, 92354, USA

    Johnny D. Figueroa

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  1. Ana E. Rodríguez-Zayas
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  2. Aranza I. Torrado
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Correspondence to Jorge D. Miranda.

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Rodríguez-Zayas, A.E., Torrado, A.I., Rosas, O.R. et al. Blockade of P2 Nucleotide Receptors After Spinal Cord Injury Reduced the Gliotic Response and Spared Tissue. J Mol Neurosci 46, 167–176 (2012). https://doi.org/10.1007/s12031-011-9567-6

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