Skip to main content

Advertisement

SpringerLink
Log in

Purinergic Regulation of Neuroinflammation in Traumatic Brain Injury

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

The purinergic system is defined as a universal regulatory system allowing individual cellular responses to be calibrated and synchronized such that they correspond to the interests of the whole body. The most important purine transmitters – ATP and adenosine – mediate positive and negative modulation of signals in the central and peripheral nervous system, the immune system, and other body systems. The synthesis and release of these transmitters, the rate of their enzymatic metabolism, and the expression of purinergic receptors significantly influence the course of normal physiological and pathological processes, including post-traumatic processes. This review addresses the main components of the purinergic system affecting the development of neuroinflammation after traumatic brain injury and the possibility of applying correction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. K. V. Shevchenko, V. A. Chetvertnykh, and Yu. I. Kravtsov, “Iummunopathological changes in severe traumatic brain injury,” Immunologiya, 30, No. 3, 180 (2009), https://www.medlit.ru/journal/403.

  2. I. A. Yankelevich, M. V. Shustov, Yu. S. Martyshkina, and T. A. Filatenkova, “Stress-induced increases in the expression of the TLR2, TLR3 and TLR4 genes in hippocampal cells,” Med. Akad. Zh., 20, No. 2, 11 (2020), https://doi.org/10.17816/MAJ33432.

    Article  Google Scholar 

  3. N. Abe, T. Nishihara, T. Yorozuya, and J. Tanaka, “Microglia and macrophages in the pathological central and peripheral nervous systems,” Cells, 9, 2132 (2020), https://doi.org/10.3390/cells9092132.

    Article  CAS  Google Scholar 

  4. O. Abiega, S. Beccari, I. Diaz-Aparicio, A. Nadjar, et al., “Neuronal hyperactivity disturbs ATP Microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling,” PLoS Biol., 14, e1002466 (2016), https://doi.org/10.1371/journal.pbio.1002554.

    Article  Google Scholar 

  5. S. L. Able, R. L. Fish, H. Bye, et al., “Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat,” Br. J. Pharmacol., 162, 405 (2011), https://doi.org/10.1111/j.1476-5381.2010.01025.x.

    Article  CAS  Google Scholar 

  6. L. Alves, R. de Melo Reis, and C. de Souza, et al., “The P2X7 receptor: shifting from a low to a high-conductance channel – an enigmatic phenomenon?” Biochim. Biophys. Acta, 1838, 2578 (2014), https://doi.org/10.1016/j.bbamem.2014.05.015.

    Article  CAS  Google Scholar 

  7. R. Andrejew, Á. Oliveira-Giacomelli, D. E. Ribeiro, et al., “The P2X7 receptor: Central hub of brain diseases,” Front. Mol. Neurosci., 31, 124 (2020), https://doi.org/10.3389/fnmol.2020.00124.

    Article  CAS  Google Scholar 

  8. T. S. Anthonymuthu, E. M. Kenny, and H. Bayır, “Therapies targeting lipid peroxidation in traumatic brain injury,” Brain Res., 1640, Part A, 57 (2016), https://doi.org/10.1016/j.brainres.2016.02.006.

  9. L. Antonioli, C. Blandizzi, P. Pacher, and G. Haskó, “The purinergic system as a pharmacological target for the treatment of immune-mediated inflammatory diseases,” Pharmacol. Rev., 71, 345 (2019), https://doi.org/10.1124/pr.117.014878.

    Article  CAS  Google Scholar 

  10. L. Antonioli, R. Colucci, C. La Motta, et al., “Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders,” Curr. Drug Targets, 13, 842 (2012), https://doi.org/10.2174/138945012800564095.

    Article  CAS  Google Scholar 

  11. L. Antonioli, M. Fornai, R. Colucci, et al., “Control of enteric neuromuscular functions by purinergic A(3) receptors in normal rat distal colon and experimental bowel inflammation,” Br. J. Pharmacol., 161, 856 (2010), https://doi.org/10.1111/j.1476-5381.2010.00917.x.

    Article  CAS  Google Scholar 

  12. L. Antonioli, P. Pacher, E. S. Vizi, and G. Haskó, “CD39 and CD73 in immunity and inflammation,” Trends Mol. Med., 19, 355 (2013), https://doi.org/10.1016/j.molmed.2013.03.005.

    Article  CAS  Google Scholar 

  13. L. Antonioli, B. Csóka, M. Fornai, et al., “Adenosine and inflammation: What’s new on the horizon?” Drug Discov. Today, 19, 1051 (2014), https://doi.org/10.1016/j.drudis.2014.02.010.

    Article  CAS  Google Scholar 

  14. A. Arac, M. A. Grimbaldeston, S. J. Galli, et al., “Meningeal mast cells as key effectors of stroke pathology,” Front. Cell. Neurosci, 13, 126 (2019), https://doi.org/10.3389/fncel.2019.00126.

    Article  CAS  Google Scholar 

  15. R. Bahri, A. Bollinger, T. Bollinger, et al., “Ectonucleotidase CD38 demarcates regulatory, memory-like CD8+ T cells with IFN-γ-mediated suppressor activities,” PLoS One, 7, e45234 (2012), https://doi.org/10.1371/journal.pone.0045234.

    Article  CAS  Google Scholar 

  16. Y. Baqi, M. Rashed, L. Schäkel, et al., “Development of anthraquinone derivatives as ectonucleoside triphosphate diphosphohydrolase (NTPDase) inhibitors with selectivity for NTPDase2 and NTPDase3,” Front. Pharmacol., 11, 1282 (2020), https://doi.org/10.3389/fphar.2020.01282.

    Article  CAS  Google Scholar 

  17. R. Bartlett, J. J. Yerbury, and R. Sluyter, “P2X7 receptor activation induces reactive oxygen species formation and cell death in murine EOC13 microglia,” Mediators Inflamm., 5, 271813 (2013), https://doi.org/10.1155/2013/271813.

    Article  CAS  Google Scholar 

  18. T. Bele and E. Fabbretti, “P2X receptors, sensory neurons and pain,” Curr. Med. Chem., 22, 845 (2015), https://doi.org/10.2174/0929867321666141011195351.

    Article  CAS  Google Scholar 

  19. M. J. Bell, P. M. Kochanek, J. A. Carcillo, et al., “Interstitial adenosine, inosine, and hypoxanthine are increased after experimental trau-Pharmatic brain injury in the rat,” J. Neurotrauma, 15, 163–70 (1998), https://doi.org/10.1089/neu.1998.15.163 PMID: 9528916.

  20. I. Bjelobaba, A. Parabucki, I. Lavrnja, et al., “Dynamic changes in the expression pattern of ecto-5’-nucleotidase in the rat model of cortical stab injury,” J. Neurosci. Res., 89, 862 (2011), https://doi.org/10.1002/jnr.22599.

    Article  CAS  Google Scholar 

  21. I. Bjelobaba, M. Stojiljkovic, I. Lavrnja, et al., “Regional changes in ectonucleotidase activity after cortical stab injury in rat,” Gen. Physiol. Biophys., 28 Special number, 62 (2009).

  22. M. L. Block, L. Zecca, and J. S. Hong, “Microglia-mediated neurotoxicity: uncovering the molecular mechanisms,” Nat. Rev. Neurosci., 8, No. 1, 57–69 (2007), https://doi.org/10.1038/nrn2038.

    Article  CAS  Google Scholar 

  23. D. Boison, “Adenosine kinase: exploitation for therapeutic gain,” Pharmacol. Rev., 65, 906 (2013), https://doi.org/10.1124/pr.112.006361.

    Article  CAS  Google Scholar 

  24. M. R. Bono, D. Fernández, F. Flores-Santibáñez, et al., “CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression,” FEBS Lett., 589, 3454 (2015), https://doi.org/10.1016/j.febslet.2015.07.027.

    Article  CAS  Google Scholar 

  25. P. A. Borea, S. Gessi, S. Merighi, et al., “Pharmacology of adenosine receptors: The state of the art,” Physiol. Rev., 98, 1591 (2018), https://doi.org/10.1152/physrev.00049.2017.

    Article  CAS  Google Scholar 

  26. P. A. Borea, S. Gessi, S. Merighi, and K. Varani, “Adenosine as a multi-signalling guardian angel in human diseases: When, where and how does it exert its protective effects?” Trends Pharmacol. Sci., 37, 419 (2016), https://doi.org/10.1016/j.tips.2016.02.006.

    Article  CAS  Google Scholar 

  27. M. Braun, K. Vaibhav, N. M. Saad, et al., “White matter damage after traumatic brain injury: A role for damage associated molecular patterns,” Biochim. Biophys. Acta Mol. Basis Dis., 1863, No. 10, Pt. B, 2614–2626 (2017), https://doi.org/10.1016/j.bbadis.2017.05.020.

  28. N. Braun, J. Sévigny, S. C. Robson, et al., “Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain,” Eur. J. Neurosci., 12, 4357 (2000), PMID: 11122346.

  29. M. Bsibsi, R. Ravid, D. Gveric, and J. M. van Noort, “Broad expression of Toll-like receptors in the human central nervous system,” J. Neuropathol. Exp. Neurol., 61, 1013 (2002), https://doi.org/10.1093/jnen/61.11.1013.

    Article  CAS  Google Scholar 

  30. G. Burnstock and J. M. Boeynaems, “Purinergic signalling and immune cells,” Purinergic Signal., 10, 529 (2014), https://doi.org/10.1007/s11302-014-9427-2.

    Article  CAS  Google Scholar 

  31. G. Burnstock, B. Dumsday, and A. Smythe, “Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide,” Br. J. Pharmacol., 44, 451 (1972).

    Article  CAS  Google Scholar 

  32. G. Burnstock and G. E. Knight, “Cellular distribution and functions of P2 receptor subtypes in different systems,” Int. Rev. Cytol., 240, 31 (2004), https://doi.org/10.1016/S0074-7696(04)40002-3, PMID:15548415.

  33. G. Burnstock, “Physiopathological roles of P2X receptors in the central nervous system,” Curr. Med. Chem., 22, 819–844 (2015), https://doi.org/10.2174/0929867321666140706130415.

    Article  CAS  Google Scholar 

  34. G. Burnstock, “Purine and pyrimidine receptors,” Cell. Mol. Life Sci., 64, 1471 (2007), https://doi.org/10.1007/s00018-007-6497-0.

    Article  CAS  Google Scholar 

  35. G. Burnstock, “Purinergic signaling in the cardiovascular system,” Circ. Res., 120, 207 (2017), https://doi.org/10.1161/CIRCRESAHA.116.309726.

    Article  CAS  Google Scholar 

  36. G. Burnstock, “Purinergic signalling and neurological diseases: An update,” CNS Neurol. Disord. Drug Targets, 16, 257 (2017), https://doi.org/10.2174/1871527315666160922104848.

    Article  CAS  Google Scholar 

  37. P. L. Capecchi, S. Rechichi, P. E. Lazzerini, et al., “Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney transplanted patients,” Transpl. Int., 18, 289–95 (2005), https://doi.org/10.1111/j.1432-2277.2004.00036.x.

    Article  CAS  Google Scholar 

  38. G. Casella, L. Garzetti, A. T. Gatta, et al., “IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo,” J. Neuroinflammation, 13, 139 (2016), https://doi.org/10.1186/s12974-016-0596-5.

    Article  CAS  Google Scholar 

  39. S. Chakravarty and M. Herkenham, “Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines,” J. Neurosci., 25, 1788 (2005), https://doi.org/10.1523/JNEUROSCI.4268-04.2005.

    Article  CAS  Google Scholar 

  40. A. M. Choo, W. J. Miller, Y. C. Chen, et al., “Antagonism of purinergic signalling improves recovery from traumatic Brain injury,” Brain, 136, Part 1, 65 (2013), https://doi.org/10.1093/brain/aws286.

  41. A. J. Cisneros-Mejorado, A. Pérez-Samartín, M. Domercq, et al., “P2X7 receptors as a therapeutic target in cerebrovascular diseases,” Front. Mol. Neurosci., 18, 92 (2020), https://doi.org/10.3389/fnmol.2020.00092.

    Article  CAS  Google Scholar 

  42. R. S. Clark, J. A. Carcillo, P. M. Kochanek, et al., “Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans,” Neurosurgery, 41, 1284 (1997), https://doi.org/10.1097/00006123-199712000-00010.

    Article  CAS  Google Scholar 

  43. M. J. Cohen, K. Brohi, M. T. Ganter, et al., “Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway,” J. Trauma, 63, 1254 (2007), https://doi.org/10.1097/TA.0b013e318156ee4c.

    Article  CAS  Google Scholar 

  44. K. N. Corps, T. L. Roth, and D. B. McGavern, “Inflammation and neuroprotection in traumatic brain injury,” JAMA Neurol., 72, 355 (2015), https://doi.org/10.1001/jamaneurol.2014.3558.

    Article  Google Scholar 

  45. J. M. Crain, M. Nikodemova, and J. J. Watters, “Expression of P2 nucleotide receptors varies with age and sex in murine brain microglia,” J. Neuroinflammation, 6: 24 (2009), https://doi.org/10.1186/1742-2094-6-24.

    Article  CAS  Google Scholar 

  46. B. N. Cronstein, M. C. Montesinos, and G. Weissmann, “Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFkappaB,” Proc. Natl. Acad. Sci. USA, 96, 6377 (1999), https://doi.org/10.1073/pnas.96.11.6377.

    Article  CAS  Google Scholar 

  47. B. N. Cronstein, “Going with the flow: methotrexate, adenosine, and blood flow,” Ann. Rheum. Dis., 65, 421 (2006), https://doi.org/10.1136/ard.2005.04960116531550.

    Article  CAS  Google Scholar 

  48. R. A. Cunha, “Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity,” Neurochem. Int., 52, 65–72 (2008), https://doi.org/10.1016/j.neuint.2007.06.026.

    Article  CAS  Google Scholar 

  49. M. Das, S. Mohapatra, and S. S. Mohapatra, “New perspectives on central and peripheral immune responses to acute traumatic brain injury,” J. Neuroinflammation, 9, 236 (2012), https://doi.org/10.1186/1742-2094-9-236.

    Article  CAS  Google Scholar 

  50. D. Davalos, J. Grutzendler, G. Yang, et al., “ATP mediates rapid microglial response to local brain injury in vivo,” Nat. Neurosci., 8, 752 (2005), https://doi.org/10.1038/nn1472.

    Article  CAS  Google Scholar 

  51. J. P. de Rivero Vaccari, G. Lotocki, O. F. Alonso, et al., “Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury,” J. Cereb. Blood Flow Metab., 29, 1251 (2009), https://doi.org/10.1038/jcbfm.2009.46.

    Article  CAS  Google Scholar 

  52. A. Del Puerto, F. Wandosell, and J. J. Garrido, “Neuronal and glial purinergic receptors functions in neuron development and brain disease,” Front. Cell. Neurosci, 7, 197 (2013), https://doi.org/10.3389/fncel.2013.0019.

    Article  Google Scholar 

  53. J. M. Deussing and E. Arzt, “P2X7 receptor: a potential therapeutic target for depression?” Trends Mol. Med., 24, 736 (2018), https://doi.org/10.1016/j.molmed.2018.07.005.

    Article  CAS  Google Scholar 

  54. R. Diaz-Arrastia, P. M. Kochanek, P. Bergold, et al., “Pharmaco–therapy of traumatic brain injury: state of the science and the road forward: report of the Department of Defense Neurotrauma Pharmacology Workgroup,” J. Neurotrauma, 31, 135 (2014), https://doi.org/10.1089/neu.2013.3019.

    Article  Google Scholar 

  55. V. Dinet, K. G. Petry, and J. Badaut, “Brain-immune interactions and neuroinflammation after traumatic brain injury,” Front. Neurosci., 13, 1178 (2019), https://doi.org/10.3389/fnins.2019.01178.

    Article  Google Scholar 

  56. A. K. Dixon, A. K. Gubitz, D. J. Sirinathsinghji, et al., “Tissue distribution of adenosine receptor mRNAs in the rat,” Br. J. Pharmacol., 118, 1461 (1996), https://doi.org/10.1111/j.1476-5381.1996.tb15561.x.

    Article  CAS  Google Scholar 

  57. C. K. Donat, G. Scott, S. M. Gentleman, and M. Sastre, “Microglial activation in traumatic brain injury,” Front. Aging Neurosci., 9, 208 (2017), https://doi.org/10.3389/fnagi.2017.00208.

    Article  CAS  Google Scholar 

  58. D. Donnelly-Roberts, S. McGaraughty, C. C. Shieh, et al., “Painful purinergic receptors,” J. Pharmacol. Exp. Ther., 324, 409 (2008), https://doi.org/10.1124/jpet.106.105890.

    Article  CAS  Google Scholar 

  59. C. R. Dorsett, J. L. McGuire, T. L. Niedzielko, et al., “traumatic brain injury induces alterations in cortical glutamate uptake without a reduction in glutamate transporter-1 protein expression,” J. Neurotrauma, 34, 220 (2017), https://doi.org/10.1089/neu.2015.4372.

    Article  Google Scholar 

  60. A. Dos Santos-Rodrigues, N. Grane-Boladeras, A. Bicket, and I. R. Coe, “Nucleoside transporters in the purinome,” Neurochem. Int., 73, 229 (2014), https://doi.org/10.1016/j.neuint.2014.03.014.

    Article  CAS  Google Scholar 

  61. C. Doyle, V. Cristofaro, M. P. Sullivan, and R. M. Adam, “Inosine – a multifunctional treatment for complications of neurologic injury,” Cell. Physiol. Biochem., 49, 2293 (2018), https://doi.org/10.1159/000493831.

    Article  CAS  Google Scholar 

  62. T. V. Dunwiddie and S. A. Masino, “The role and regulation of adenosine in the central nervous system,” Annu. Rev. Neurosci., 24, 31 (2001), https://doi.org/10.1146/annurev.neuro.24.1.31.

    Article  CAS  Google Scholar 

  63. M. J. During and D. D. Spencer, “Adenosine: A potential mediator of seizure arrest and postictal refractoriness,” Ann. Neurol., 32, 618 (1992), https://doi.org/10.1002/ana.410320504.

    Article  CAS  Google Scholar 

  64. W. I. Effendi, T. Nagano, K. Kobayashi, and Y. Nishimura, “Focusing on adenosine receptors as a potential targeted therapy in human diseases,” Cells, 9, 785 (2020), https://doi.org/10.3390/cells9030785.

    Article  CAS  Google Scholar 

  65. H. K. Eltzschig, M. Faigle, S. Knapp, et al., “Endothelial catabolism of extracellular adenosine during hypoxia: The role of surface adenosine deaminase and CD26,” Blood, 108, 1602 (2006), https://doi.org/10.1182/blood-2006-02-001016.

    Article  CAS  Google Scholar 

  66. D. F. Emerich, R. L. Dean, 3rd, and R. T. Bartus, “The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct?” Exp. Neurol., 173, 168–81 (2002), https://doi.org/10.1006/exnr.2001.7835.

    Article  Google Scholar 

  67. A. Eser, J. F. Colombel, P. Rutgeerts, et al., “Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active Crohn’s disease: A Randomized placebo-controlled, double-blind, phase IIa study,” Inflamm. Bowel Dis., 21, 2247 (2015), https://doi.org/10.1097/MIB.0000000000000514.

    Article  Google Scholar 

  68. K. M. Fang, C. S. Yang, S. H. Sun, and S. F. Tzeng, “Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X receptor action,” J. Neurochem., 111, 1225–37 (2009), https://doi.org/10.1111/j.1471-4159.2009.06409.x.

    Article  CAS  Google Scholar 

  69. S. A. Farr, S. Cuzzocrea, E. Esposito, et al., “Adenosine A3 receptor as a novel therapeutic target to reduce secondary events and improve neurocognitive functions following traumatic brain injury,” J. Neuroinflammation, 17, 339 (2020), https://doi.org/10.1186/s12974-020-02009-7.

    Article  CAS  Google Scholar 

  70. R. D. Fields and B. Stevens, “ATP: an extracellular signaling molecule between neurons and glia,” Trends Neurosci., 23, 625 (2000), https://doi.org/10.1016/s0166-2236(00)01674-x.

    Article  CAS  Google Scholar 

  71. R. Franco and D. Fernandez-Suarez, “Alternatively activated microglia and macrophages in the central nervous system,” Prog. Neurobiol., 131, 65 (2015), https://doi.org/10.1016/j.pneurobio.2015.05.003.

    Article  CAS  Google Scholar 

  72. H. Franke, U. Krügel, and P. Illes, “P2 receptors and neuronal injury,” Pflugers Arch., 452, 622 (2006), https://doi.org/10.1007/s00424-006-0071-8.

    Article  CAS  Google Scholar 

  73. H. Franke, C. Schepper, P. Illes, and U. Krugel, “Involvement of P2X and P2Y receptors in microglial activation in vivo,” Purinergic Signal., 3, 435 (2007), https://doi.org/10.1007/s11302-007-9082-y.

    Article  CAS  Google Scholar 

  74. M. Ganesana and B. J. Venton, “Early changes in transient adenosine during cerebral ischemia and reperfusion injury,” PLoS One, 13, e0196932 (2018), https://doi.org/10.1371/journal.pone.0196932.

    Article  CAS  Google Scholar 

  75. H. M. Gebril, R. M. Rose, R. Gesese, et al., “Adenosine kinase inhibition promotes proliferation of neural stem cells after traumatic brain injury,” Brain Commun., 2, fcaa017 (2020), https://doi.org/10.1093/braincomms/fcaa017.

  76. J. R. Gever, D. A. Cockayne, M. P. Dillon, et al., “Pharmacology of P2X channels,” Pflugers Arch., 452, 513–37 (2006), https://doi.org/10.1007/s00424-006-0070-9.

    Article  CAS  Google Scholar 

  77. D. F. Gilbert, M. J. Stebbing, K. Kuenzel, et al., “Store-operated Ca2+ entry (SOCE) and purinergic receptor-mediated Ca2+ homeostasis in murine bv2 microglia cells: Early cellular responses to ATP-mediated microglia activation,” Front. Mol. Neurosci., 28, 111 (2016), https://doi.org/10.3389/fnmol.2016.00111.

    Article  CAS  Google Scholar 

  78. A. L. Giuliani, A. C. Sarti, S. Falzoni, and F. Di Virgilio, “The P2X7 receptor-interleukin-1 liaison,” Front. Pharmacol., 8, 123, (2017), https://doi.org/10.3389/fphar.2017.00123.

  79. J. J. V. Gompel, M. R. Bower, G. A. Worrell, et al., “Increased cortical extracellular adenosine correlates with seizure termination,” Epilepsia, 55, 233 (2014), https://doi.org/10.1111/epi.12511.

    Article  CAS  Google Scholar 

  80. G. Gruenbacher, H. Gander, A. Rahm, et al., “The human G protein-coupled ATP receptor P2Y11 is associated with IL-10 driven macrophage differentiation,” Front. Immunol., 10, 1870 (2019), https://doi.org/10.3389/fimmu.2019.018700.

    Article  CAS  Google Scholar 

  81. S. V. Gudkov, I. N. Shtarkman, V. S. Smirnova, et al., “Guanosine and inosine as natural antioxidants and radioprotectors for mice exposed to lethal doses of gamma-radiation,” Dokl. Biochem. Biophys., 407, 47 (2006), https://doi.org/10.1134/s1607672906020013.

    Article  CAS  Google Scholar 

  82. M. M. Halassa, T. Fellin, and P. G. Haydon, “The tripartite synapse: roles for gliotransmission in health and disease,” Trends Mol. Med., 13, 54 (2007), https://doi.org/10.1016/j.molmed.2006.12.005.

    Article  CAS  Google Scholar 

  83. U. K. Hanisch and H. Kettenmann, “Microglia: active sensor and versatile effector cells in the normal and pathologic brain,” Nat. Neurosci., 10, 1387 (2007), https://doi.org/10.1038/nn1997.

    Article  CAS  Google Scholar 

  84. M. L. Haselkorn, D. K. Shellington, E. K. Jackson, et al., “Adenosine A1 receptor activation as a brake on the microglial response after experimental traumatic brain injury in mice,” J. Neurotrauma, 27, 901 (2010), https://doi.org/10.1089/neu.2009.1075.

    Article  Google Scholar 

  85. G. Haskó, L. Antonioli, and B. N. Cronstein, “Adenosine metabolism, immunity and joint health,” Biochem. Pharmacol., 151, 307 (2018), https://doi.org/10.1016/j.bcp.2018.02.002.

    Article  CAS  Google Scholar 

  86. G. Haskó, M. V. Sitkovsky, and C. Szabó, “Immunomodulatory and neuroprotective effects of inosine,” Trends Pharmacol. Sci., 25, 152 (2004), https://doi.org/10.1016/j.tips.2004.01.006.

    Article  CAS  Google Scholar 

  87. P. G. Haydon and G. Carmignoto, “Astrocyte control of synaptic transmission and neurovascular coupling,” Physiol. Rev., 86, 1009 (2006), https://doi.org/10.1152/physrev.00049.2005.

    Article  CAS  Google Scholar 

  88. S. E. Haynes, G. Hollopeter, G. Yang, et al., “The P2Y12 receptor regulates microglial activation by extracellular nucleotides,” Nat. Neurosci., 12, 1512 (2006), https://doi.org/10.1038/nn1805.

    Article  CAS  Google Scholar 

  89. J. Hazeldine, J. M. Lord, and A. Belli, “Traumatic brain injury and peripheral immune suppression: primer and prospectus,” Front. Neurol., 6, 235 (2015), https://doi.org/10.3389/fneur.2015.00235.

    Article  Google Scholar 

  90. H. Hirbec, F. Rassendren, and E. Audinat, “Microglia reactivity: Heterogeneous pathological phenotypes,” Methods Mol. Biol., 2034, 41 (2019), https://doi.org/10.1007/978-1-4939-9658-2_4.

    Article  CAS  Google Scholar 

  91. A. L. Horenstein, A. Chillemi, G. Zaccarello, et al., “A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes,” Oncoimmunology, 2, e26246 (2013), https://doi.org/10.4161/onci.26246.

    Article  Google Scholar 

  92. A. L. Horenstein, V. Quarona, D. Toscani, et al., “Adenosine generated in the bone marrow niche through a CD38-mediated pathway correlates with progression of human myeloma,” Mol. Med., 22, 694 (2016), https://doi.org/10.2119/molmed.2016.00198.

    Article  CAS  Google Scholar 

  93. B. R. Huber, J. S. Meabon, Z. S. Hoffer, et al., “Blast exposure causes dynamic microglial/macrophage responses and microdomains of brain microvessel dysfunction,” Neuroscience, 319, 206 (2016), https://doi.org/10.1016/j.neuroscience.2016.01.022.

    Article  CAS  Google Scholar 

  94. P. Illes, P. Rubini, H. Ulrich, et al., “Regulation of microglial functions by purinergic mechanisms in the healthy and diseased CNS,” Cells, 9, 1108 (2020), https://doi.org/10.3390/cells9051108.

    Article  CAS  Google Scholar 

  95. K. A. Jacobson and C. E. Müller, “Medicinal chemistry of adenosine, P2Y and P2X receptors,” Neuropharmacology, 104, 31 (2016), https://doi.org/10.1016/j.neuropharm.2015.12.001.

    Article  CAS  Google Scholar 

  96. A. Jarrahi, M. Braun, and M. Ahluwalia, et al., “revisiting traumatic brain injury: From molecular mechanisms to therapeutic interventions,” Biomedicines, 8, 389 (2020), https://doi.org/10.3390/biomedicines8100389.

    Article  CAS  Google Scholar 

  97. Y. N. Jassam, S. Izzy, M. Whalen, et al., “Neuroimmunology of traumatic brain injury: Time for a paradigm shift,” Neuron, 95, 1246 (2017), https://doi.org/10.1016/j.neuron.2017.07.010.

    Article  CAS  Google Scholar 

  98. S. Y. Jeong, R. Jeon, Y. K. Choi, et al., “Activation of microglial Toll-like receptor 3 promotes neuronal survival against cerebral ischemia,” J. Neurochem., 136, 851 (2016), https://doi.org/10.1111/jnc.13441.

    Article  CAS  Google Scholar 

  99. W. Jin, W. Xu, J. Chen, et al., “Adenosine kinase facilitated astrogliosis-induced cortical neuronal death in traumatic brain injury,” J. Mol. Histol., 47, 259 (2016), https://doi.org/10.1007/s10735-016-9670-7.

    Article  CAS  Google Scholar 

  100. A. Karasawa and T. Kawate, “Structural basis for subtype-specific inhibition of the P2X7 receptor,” eLife, 5, e22153 (2016), https://doi.org/10.7554/eLife.22153.

    Article  Google Scholar 

  101. M. Karmakar, M. A. Katsnelson, G. R. Dubyak, and E. Pearlman, “Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP,” Nat. Commun., 7, 10555 (2016), https://doi.org/10.1038/ncomms10555.

    Article  CAS  Google Scholar 

  102. N. Kelley, D. Jeltema, Y. Duan, and Y. He, “The NLRP3 inflammasome: An overview of mechanisms of activation and regulation,” Int. J. Mol. Sci., 20, 3328 (2019), https://doi.org/10.3390/ijms20133328.

    Article  CAS  Google Scholar 

  103. D. Kempuraj, M. E. Ahmed, G. P. Selvakumar, et al., “Mast cell activation, neuroinflammation, and tight junction protein derangement in acute traumatic brain injury,” Mediators Inflamm., 2020, 4243953 (2020), https://doi.org/10.1155/2020/4243953.

    Article  CAS  Google Scholar 

  104. E. C. Keystone, M. M. Wang, M. Layton, et al., “Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine,” Ann. Rheum. Dis., 71, 1630 (2012), https://doi.org/10.1136/annrheumdis-2011-143578.

    Article  CAS  Google Scholar 

  105. K. A. Kigerl, J. C. Gensel, D. P. Ankeny, et al., “Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord,” J. Neurosci., 29, 13435 (2009), https://doi.org/10.1523/JNEUROSCI.3257-09.2009.

    Article  CAS  Google Scholar 

  106. E. Kim, E. C. Lauterbach, A. Reeve, et al., “Neuropsychiatric complications of traumatic brain injury: a critical review of the literature (a report by the ANPA Committee on Research),” J. Neuropsychiatr. Clin. Neurosci., 19, 106 (2007), https://doi.org/10.1176/jnp.2007.19.2.106.

    Article  Google Scholar 

  107. S. W. Kim, D. Davaanyam, S. I. Seol, et al., “Adenosine triphosphate accumulated following cerebral ischemia induces neutrophil extracellular trap formation,” Int. J. Mol. Sci., 21, 7668 (2020), https://doi.org/10.3390/ijms21207668.

    Article  CAS  Google Scholar 

  108. D. E. Kimbler, J. Shields, N. Yanasak, et al., “Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice,” PLoS One, 7, e41229 (2012), https://doi.org/10.1371/journal.pone.0041229.

    Article  CAS  Google Scholar 

  109. H. Koizumi, M. Arito, W. Endo, et al., “Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes,” Mod. Rheumatol., 25, 522 (2015), https://doi.org/10.3109/14397595.2014.995874.

    Article  CAS  Google Scholar 

  110. S. Koizumi, K. Ohsawa, K. Inoue, and S. Kohsaka, “Purinergic receptors in microGlia: Functional modal shifts of microGlia mediated by P2 and P1 receptors,” Glia, 61, 47 (2013), https://doi.org/10.1002/glia.22358.

    Article  Google Scholar 

  111. V. Kumar, “Toll-like receptors in the pathogenesis of neuroinflammation,” J. Neuroimmunol., 332, 16 (2019), https://doi.org/10.1016/j.jneuroim.2019.03.012.

    Article  CAS  Google Scholar 

  112. S. Latini and F. Pedata, “Adenosine in the central nervous system: release mechanisms and extracellular concentrations,” J. Neurochem., 79, 463 (2001), https://doi.org/10.1046/j.1471-4159.2001.00607.x.

    Article  CAS  Google Scholar 

  113. E. R. Lazarowski, “Vesicular and conductive mechanisms of nucleotide release,” Purinergic Signal., 8, 359 (2012), https://doi.org/10.1007/s11302-012-9304-9.

    Article  CAS  Google Scholar 

  114. J. Li, E. R. Ramenaden, J. Peng, et al., “Tumor necrosis factor α mediates lipopolysaccharide-induced microglial toxicity to developing oligodendrocytes when astrocytes are present,” J. Neurosci., 28, 5321 (2008), https://doi.org/10.1523/JNEUROSCI.3995-07.2008.

    Article  CAS  Google Scholar 

  115. F. Lipmann, Adv. Enzymol., 1, 99 (1941), https://doi.org/10.1002/9780470122464.ch4.

    Article  CAS  Google Scholar 

  116. X. Liu, Z. Zhao, R. Ji, et al., “Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats,” Purinergic Signal., 13, 529 (2017), https://doi.org/10.1007/s11302-017-9579-y.

    Article  CAS  Google Scholar 

  117. L. Luongo, F. Guida, R. Imperatore, et al., “The A1 adenosine receptor as a new player in microglia physiology,” Glia, 62, 122 (2014), https://doi.org/10.1002/glia.22592.

    Article  CAS  Google Scholar 

  118. T. A. Lusardi, “Adenosine neuromodulation and traumatic brain injury,” Curr. Neuropharmacol., 7, 228 (2009), https://doi.org/10.2174/157015909789152137.

    Article  CAS  Google Scholar 

  119. C. E. Markowitz, S. Spitsin, V. Zimmerman, et al., “The treatment of multiple sclerosis with inosine,” J. Altern. Complement Med., 15, 619 (2009), https://doi.org/10.1089/acm.2008.0513.

    Article  Google Scholar 

  120. F. O. Martinez, A. Sica, A. Mantovani, and M. Locati, “Macrophage activation and polarization,” Front. Biosci., 13, 453 (2008), https://doi.org/10.2741/2692.

    Article  CAS  Google Scholar 

  121. C. Matute, “P2X7 receptors in oligodendrocytes: a novel target for neuroprotection,” Mol. Neurobiol., 38, 123 (2008), https://doi.org/10.1007/s12035-008-8028-x.

    Article  CAS  Google Scholar 

  122. K. McInnes, C. L. Friesen, D. E. MacKenzie, et al., “Mild traumatic brain injury (mTBI) and chronic cognitive impairment: A scoping review,” PLoS One, 12, e0174847 (2017), https://doi.org/10.1371/journal.pone.0174847.

    Article  CAS  Google Scholar 

  123. F. Meng, Z. Guo, Y. Hu, et al., “CD73-derived adenosine controls inflammation and neurodegeneration by modulating dopamine signaling,” Brain, 142, 700 (2019), https://doi.org/10.1093/brain/awy351.

    Article  Google Scholar 

  124. S. Merighi, E. Battistello, L. Giacomelli, et al., “Targeting A3 and A2A adenosine receptors in the fight against cancer,” Expert Opin. Ther. Targets, 23, 669–678 (2019), https://doi.org/10.1080/14728222.2019.1630380.

    Article  CAS  Google Scholar 

  125. G. Milior, M. Morin-Brureau, F. Chali, et al., “Distinct P2Y receptors mediate extension and retraction of microglial processes in epileptic and peritumoral human tissue,” J. Neurosci., 40, 1373 (2020), https://doi.org/10.1523/JNEUROSCI.0218-19.2019.

    Article  CAS  Google Scholar 

  126. L. Morabito, M. C. Montesinos, D. M. Schreibman, et al., “Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5’-nucleotidase-mediated conversion of adenine nucleotides,” J. Clin. Invest., 101, 295–300 (1998), https://doi.org/10.1172/JCI1554.

    Article  CAS  Google Scholar 

  127. J. C. Morote-Garcia, P. Rosenberger, J. Kuhlicke, and H. K. Eltzschig, “HIF-1-dependent repression of adenosine kinase attenuates hypoxia-induced vascular leak,” Blood, 111, 5571 (2008), https://doi.org/10.1182/blood-2007-11-126763.

    Article  CAS  Google Scholar 

  128. M. Morra, M. Zubiaur, C. Terhorst, et al., “CD38 is functionally dependent on the TCR/CD3 complex in human T cells,” FASEB J., 12, 581 (1998), https://doi.org/10.1096/fasebj.12.7.581.

    Article  CAS  Google Scholar 

  129. P. J. Murray, J. E. Allen, S. K. Biswas, et al., “Macrophage activation and polarization: Nomenclature and experimental guidelines,” Immunity, 41, 14 (2014), https://doi.org/10.1016/j.immuni.2014.06.008.

    Article  CAS  Google Scholar 

  130. C. A. Mutch, J. F. Talbott, and A. Gean, “Imaging evaluation of acute traumatic brain injury,” Neurosurg. Clin. N. Am., 27, 409 (2016), https://doi.org/10.1016/j.nec.2016.05.011.

    Article  Google Scholar 

  131. K. Nakajima, Y. Tohyama, S. Maeda, et al., “Neuronal regulation by which microglia enhance the production of neurotrophic factors for GABAergic, catecholaminergic, and cholinergic neurons,” Neurochem. Int., 50, 807–20 (2007), https://doi.org/10.1016/j.neuint.2007.02.006.

    Article  CAS  Google Scholar 

  132. N. Nedeljkovic, I. Bjelobaba, I. Lavrnja, et al., “Early temporal changes in ecto-nucleotidase activity after cortical stab injury in rat,” Neurochem. Res., 33, 873 (2008), https://doi.org/10.1007/s11064-007-9529-0.

    Article  CAS  Google Scholar 

  133. R. Nguyen, K. M. Fiest, J. McChesney, et al., “The international incidence of traumatic brain injury: A systematic review and meta-analysis,” Can. J. Neurol. Sci., 43, 774 (2016), https://doi.org/10.1017/cjn.2016.290.

    Article  Google Scholar 

  134. J. Niemelä, I. Ifergan, G. G. Yegutkin, et al., “IFN-beta regulates CD73 and adenosine expression at the blood–brain barrier,” Eur. J. Immunol., 38, 2718 (2008), https://doi.org/10.1002/eji.200838437.

    Article  CAS  Google Scholar 

  135. A. Nimmerjahn, F. Kirchhoff, and F. Helmchen, “Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo,” Science, 308, 1314 (2005), https://doi.org/10.1126/science.1110647.

    Article  CAS  Google Scholar 

  136. K. Ohsawa, Y. Irino, Y. Nakamura, et al., “Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis,” Glia, 55, 604 (2007), https://doi.org/10.1002/glia.20489.

    Article  Google Scholar 

  137. J. K. Olson and S. D. Miller, “Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs,” J. Immunol., 173, 3916 (2004), https://doi.org/10.4049/jimmunol.173.6.3916.

    Article  CAS  Google Scholar 

  138. C. Palmer, R. L. Roberts, and P. I. Young, “Timing of neutrophil depletion influences long-term neuroprotection in neonatal rat hypoxic-ischemic brain injury,” Pediatr. Res., 55, 549 (2004), https://doi.org/10.1203/01.PDR.0000113546.03897.FC.

  139. A. J. Pawson, J. L. Sharman, H. E. Benson, et al., “The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands,” Nucleic Acids Res., 42 (database issue): D1098-106 (2014), https://doi.org/10.1093/nar/gkt1143.

  140. F. Pedata, A. Melani, A. M. Pugliese, et al., “The role of ATP and adenosine in the brain under normoxic and ischemic conditions,” Purinergic Signal., 3, 299 (2007), https://doi.org/10.1007/s11302-007-9085-8.

    Article  CAS  Google Scholar 

  141. F. Pedata, I. Dettori, E. Coppi, et al., “Purinergic signalling in brain ischemia,” Neuropharmacology, 104, 105 (2016), https://doi.org/10.1016/j.neuropharm.2015.11.007.

    Article  CAS  Google Scholar 

  142. V. H. Perry, J. A. Nicoll, and C. Holmes, “Microglia in neurodegenerative disease,” Nat. Dev. Neurol., 6, 193 (2010), https://doi.org/10.1038/nrneurol.2010.17.

    Article  Google Scholar 

  143. V. Quarona, G. Zaccarello, A. Chillemi, et al., “CD38 and CD157: a long journey from activation markers to multifunctional molecules,” Cytometry B Clin. Cytom., 84, 207 (2013), https://doi.org/10.1002/cyto.b.21092.

    Article  CAS  Google Scholar 

  144. B. Relja and W. G. Land, “Damage-associated molecular patterns in trauma,” Eur. J. Trauma Emerg. Surg., 46, 751 (2020), https://doi.org/10.1007/s00068-019-01235-w.

    Article  Google Scholar 

  145. C. L. Robertson, M. J. Bell, P. M. Kochanek, et al., “Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity,” Crit. Care Med., 29, 2287 (2001), https://doi.org/10.1097/00003246-200112000-00009.

    Article  CAS  Google Scholar 

  146. K. Roszek and J. Czarnecka, “Is ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)-based therapy of central nervous system disorders possible?” Mini Rev Med. Chem., 15, 5 (2015), https://doi.org/10.2174/1389557515666150219114416.

    Article  CAS  Google Scholar 

  147. T. L. Roth, D. Nayak, T. Atanasijevic, et al., “Transcranial amelioration of inflammation and cell death after brain injury,” Nature, 505, 223 (2014), https://doi.org/10.1038/nature12808.

    Article  CAS  Google Scholar 

  148. P. Ruhal and D. Dhingra, “Inosine improves cognitive function and decreases aging-induced oxidative stress and neuroinflammation in aged female rats,” Inflammopharmacology, 26, 1317 (2018), https://doi.org/10.1007/s10787-018-0476-y.

    Article  CAS  Google Scholar 

  149. M. Schilling, J. K. Strecker, E. B. Ringelstein, et al., “The role of CC chemokine receptor 2 on microglia activation and blood-borne cell recruitment after transient focal cerebral ischemia in mice,” Brain Res., 1289, 79 (2009), https://doi.org/10.1016/j.brainres.2009.06.054.

    Article  CAS  Google Scholar 

  150. M. Schneider, K. Prudic, A. Pippel, et al., “Interaction of purinergic P2X4 and P2X7 receptor subunits,” Front. Pharmacol., 8, 860 (2017), https://doi.org/10.3389/fphar.2017.00860.

    Article  CAS  Google Scholar 

  151. V. M. Sciotti and D. G. Van Wylen, “Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase,” J. Cereb. Blood Flow Metab., 13, 201 (1993), https://doi.org/10.1038/jcbfm.1993.24.

    Article  CAS  Google Scholar 

  152. S. Sheth, R. Brito, D. Mukherjea, et al., “Adenosine receptors: expression, function and regulation,” Int. J. Mol. Sci., 15, 2024, https://doi.org/10.3390/ijms15022024.

  153. D. W. Simon, M. J. McGeachy, H. Bayır, et al., “The far-reaching scope of neuroinflammation after traumatic brain injury,” Nat. Dev. Neurol., 13, 171 (2017), https://doi.org/10.1038/nrneurol.2017.13.

    Article  Google Scholar 

  154. G. Sipe, R. Lowery, M. È. Tremblay, et al., “Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex,” Nat. Commun., 7, 10905 (2016), https://doi.org/10.1038/ncomms10905.

    Article  CAS  Google Scholar 

  155. A. Solini, P. Chiozzi, A. Morelli, et al., “Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release,” J. Cell Sci., 112, 297; PMID: 9885283 (1999).

  156. R. Sluyter, J. G. Dalitz, and J. S. Wiley, “P2X7 receptor polymorphism impairs extracellular adenosine 5'-triphosphate-induced interleukin-18 release from human monocytes,” Genes Immun., 5, 588 (2004), https://doi.org/10.1038/sj.gene.6364127.

    Article  CAS  Google Scholar 

  157. A. Sofoluwe, M. Bacchetta, M. Badaoui, et al., “ATP amplifies NADPH-dependent and -independent neutrophil extracellular trap formation,” Sci. Rep., 9, 16556 (2019), https://doi.org/10.1038/s41598-019-53058-9.

    Article  CAS  Google Scholar 

  158. B. Sperlágh, E. S. Vizi, K. Wirkner, and P. Illes, “P2X7 receptors in the nervous system,” Prog. Neurobiol., 78, 327 (2006), https://doi.org/10.1016/j.pneurobio.2006.03.007.

    Article  CAS  Google Scholar 

  159. S. Spitsin, D. C. Hooper, T. Leist, et al., “Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease,” Mult. Scler., 7, 313 (2001), https://doi.org/10.1177/135245850100700507.

    Article  CAS  Google Scholar 

  160. T. C. Stock, B. J. Bloom, N. Wei, et al., “Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate,” J. Rheumatol., 39, 720 (2012), https://doi.org/10.3899/jrheum.110874.

    Article  CAS  Google Scholar 

  161. L. Talley Watts, S. Sprague, W. Zheng, et al., “Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model,” J. Neurotrauma, 30, 55 (2013), https://doi.org/10.1089/neu.2012.2488.

    Article  Google Scholar 

  162. A. Taruno, “ATP release channels,” Int. J. Mol. Sci., 19, 808 (2018), https://doi.org/10.3390/ijms19030808.

    Article  CAS  Google Scholar 

  163. F. C. Teixeira, J. M. Gutierres, M. S. P. Soares, et al., “Inosine protects against impairment of memory induced by experimental model of Alzheimer disease: a nucleoside with multitarget brain actions,” Psychopharmacology (Berlin), 237, 811 (2020), https://doi.org/10.1007/s00213-019-05419-5.

    Article  CAS  Google Scholar 

  164. A. Trautmann, “Extracellular ATP in the immune system: more than just a “danger signal”,” Sci. Signal, 2, pe6 (2009), https://doi.org/10.1126/scisignal.256pe6.

    Article  CAS  Google Scholar 

  165. J. F. Vazquez, H. W. Clement, O. Sommer, et al., “Local stimulation of the adenosine A2B receptors induces an increased release of IL-6 in mouse striatum: an in vivo microdialysis study,” J. Neurochem., 105, 904 (2008), https://doi.org/10.1111/j.1471-4159.2007.05191.x.

    Article  CAS  Google Scholar 

  166. G. Veres, T. Radovits, L. Seres, et al., “Effects of inosine on reperfusion injury after cardiopulmonary bypass,” J. Cardiothorac. Surg., 5, 106 (2010), https://doi.org/10.1186/1749-8090-5-106.

    Article  Google Scholar 

  167. P. Vespa, M. Bergsneider, N. Hattori, et al., “Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study,” J. Cereb. Blood Flow Metab., 25, 763 (2005), https://doi.org/10.1038/sj.jcbfm.9600073.

    Article  CAS  Google Scholar 

  168. F. Vincenzi, S. Pasquini, P. A. Borea, and K. Varani, “Targeting adenosine receptors: A potential pharmacological avenue for acute and chronic pain,” Int. J. Mol. Sci., 21, 8710 (2020), https://doi.org/10.3390/ijms21228710.

    Article  CAS  Google Scholar 

  169. I. von Kügelgen, “Pharmacological profiles of cloned mammalian P2Y-receptor subtypes,” Pharmacol. Ther., 110, 415 (2006), https://doi.org/10.1016/j.pharmthera.2005.08.014.

    Article  CAS  Google Scholar 

  170. K. R. Walker and G. Tesco, “Molecular mechanisms of cognitive dysfunction following traumatic brain injury,” Front. Aging Neurosci., 5, 29 (2013), https://doi.org/10.3389/fnagi.2013.00029.

    Article  Google Scholar 

  171. Z. Xiang, M. Chen, J. Ping, et al., “Microglial morphology and its transformation after challenge by extracellular ATP in vitro,” J. Neurosci. Res., 83, 91 (2006), https://doi.org/10.1002/jnr.20709.

    Article  CAS  Google Scholar 

  172. H. Zarrinmayeh and P. Territo, “Purinergic receptors of the central nervous system: Biology, PET ligands, and their applications,” Mol. Imaging, 19, 1 (2020), https://doi.org/10.1177/1536012120927609.

    Article  CAS  Google Scholar 

  173. A. M. Zhou, W. B. Li, Q. J. Li, et al., “A short cerebral ischemic preconditioning up-regulates adenosine receptors in the hippocampal CA1 region of rats,” Neurosci. Res., 48, 397 (2004), https://doi.org/10.1016/j.neures.2003.12.010.

    Article  CAS  Google Scholar 

  174. H. Zimmermann, “Extracellular metabolism of ATP and other nucleotides,” Naunyn Schmiedebergs Arch. Pharmacol., 362, 299 (2000), https://doi.org/10.1007/s002100000309.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Experimental Medicine, Russian Federation Ministry of Education and Science, St. Petersburg, Russia

    N. B. Serebryanaya & E. E. Fomicheva

  2. St. Petersburg Peter the Great Polytechnic University, Russian Federation Ministry of Education and Science, St. Petersburg, Russia

    P. P. Yakutseni

Authors
  1. N. B. Serebryanaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. E. Fomicheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. P. Yakutseni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. B. Serebryanaya.

Additional information

Translated from Uspekhi Fiziologicheskikh Nauk, Vol. 52, No. 3, pp. 24–40, July–September, 2021.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Serebryanaya, N.B., Fomicheva, E.E. & Yakutseni, P.P. Purinergic Regulation of Neuroinflammation in Traumatic Brain Injury. Neurosci Behav Physi 52, 1093–1106 (2022). https://doi.org/10.1007/s11055-022-01337-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-022-01337-w

Keywords

Search

Navigation