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Platelet-rich Plasma Improves Radiotherapy-induced Emotional Disorder and Cognitive Dysfunction, Neuroinflammation in Aged Rats by Inhibiting the Activation of NLRP3 Inflammasomes

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Abstract

Although radiotherapy (RT) is the preferred treatment for elderly patients with brain tumors, certain negative effects can’t be ignored. Fortunately, platelet-rich plasma (PRP) presents with a promising potential for the treatment of neurological diseases. Therefore, this study aimed to explore the effect of PRP on neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats. Firstly, whole brain RT (WBRT) model was established by whole brain irradiation with 10 Gy of 6-MeV electron beam in rats. Next, twenty 20-month-old female SD rats were divided into four groups (sham group, PRP group, WBRT group, and WBRT + PRP group) according different treatments. After that, the cognitive dysfunction and depression-like behavior of rats were examined by novel object recognition test (NORT), Morris water maze test (MWM), open field test (OFT) and elevated plus maze test (EPM). Besides, immunohistochemistry was used to detect the expression of microglial marker protein Iba-1 in rat hippocampus; enzyme linked immunosorbent assay (ELISA) to examine the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (IL-1β), IL-18, and monocyte chemoattractant protein 1 (MCP-1) in rat hippocampus; real-time quantitative reverse transcription PCR (qRT-PCR) and western blot to measure the levels of neurotrophic factors brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B receptor (TrkB), and nerve growth factor (NGF) in rat hippocampus; and western blot also to observe the protein expression levels of NOD-like receptor protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and IL-1β in rat hippocampus. After experiments, some results obtained were shown as follows. PRP could significantly improve learning and memory ability and depression-like behavior, increase the level of neurotrophic factors, inhibit the activation of microglia and decrease the level of pro-inflammatory factors in WBRT rats. In addition, PRP significantly inhibited the activation of NLRP3 inflammasomes. To sum up, PRP can ameliorate neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats, and the mechanism may be related to its inhibitory effect on NLRP3 inflammasome activation.

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Data Availability

The datasets used and analysed in the current study are available from the corresponding author on reasonable request.

References

  1. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, Alteri R, Robbins AS, Jemal A (2014) Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 64:252–271. https://doi.org/10.3322/caac.21235

    Article  PubMed  Google Scholar 

  2. Makale MT, McDonald CR, Hattangadi-Gluth JA, Kesari S (2017) Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours. Nat Rev Neurol 13:52–64. https://doi.org/10.1038/nrneurol.2016.185

    Article  CAS  PubMed  Google Scholar 

  3. Mitchell TJ, Seitzman BA, Ballard N, Petersen SE, Shimony JS, Leuthardt EC (2020) Human brain Functional Network Organization is disrupted after whole-brain Radiation Therapy. Brain Connect 10:29–38. https://doi.org/10.1089/brain.2019.0713

    Article  PubMed  PubMed Central  Google Scholar 

  4. Surendran HP, Narmadha MP, Kalavagunta S, Sasidharan A, Dutta D (2022) Preservation of cognitive function after brain irradiation. J Oncol Pharm practice: official publication Int Soc Oncol Pharm Practitioners 10781552221077037 Advance online publication. https://doi.org/10.1177/10781552221077037

  5. Lutz ST, Jones J, Chow E (2014) Role of radiation therapy in palliative care of the patient with cancer. J Clin Oncol 32:2913–2919. https://doi.org/10.1200/JCO.2014.55.1143

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nayak D, Roth TL, McGavern DB (2014) Microglia development and function. Annu Rev Immunol 32:367–402. https://doi.org/10.1146/annurev-immunol-032713-120240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kwon HS, Koh SH (2020) Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl Neurodegener 9:42. https://doi.org/10.1186/s40035-020-00221-2

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhao J, Bi W, Xiao S, Lan X, Cheng X, Zhang J, Lu D, Wei W, Wang Y, Li H, Fu Y, Zhu L (2019) Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice. Sci Rep 9:5790. https://doi.org/10.1038/s41598-019-42286-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu YG, Chen JK, Zhang ZT, Ma XJ, Chen YC, Du XM, Liu H, Zong Y, Lu GC (2017) NLRP3 inflammasome activation mediates radiation-induced pyroptosis in bone marrow-derived macrophages. Cell Death Dis 8:e2579. https://doi.org/10.1038/cddis.2016.460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wei J, Wang H, Wang H, Wang B, Meng L, Xin Y, Jiang X (2019) The role of NLRP3 inflammasome activation in radiation damage. Biomed Pharmacother 118:109217. https://doi.org/10.1016/j.biopha.2019.109217

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z (2019) Embelin improves the spatial memory and hippocampal long-term potentiation in a rat model of chronic cerebral hypoperfusion. Sci Rep 9:14507. https://doi.org/10.1038/s41598-019-50954-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zhang Y, Ying G, Ren C, Jizhang Y, Brogan D, Liu Z, Li S, Ding Y, Borlongan CV, Zhang J, Ji X (2015) Administration of human platelet-rich plasma reduces infarction volume and improves motor function in adult rats with focal ischemic stroke. Brain Res 1594:267–273. https://doi.org/10.1016/j.brainres.2014.10.035

    Article  CAS  PubMed  Google Scholar 

  14. Emer J (2019) Platelet-Rich plasma (PRP): current applications in Dermatology. Skin Therapy Lett 24:1–6

    PubMed  Google Scholar 

  15. Bayat M, Zabihi S, Karbalaei N, Haghani M (2020) Time-dependent effects of platelet-rich plasma on the memory and hippocampal synaptic plasticity impairment in vascular dementia induced by chronic cerebral hypoperfusion. Brain Res Bull 164:299–306. https://doi.org/10.1016/j.brainresbull.2020.08.033

    Article  CAS  PubMed  Google Scholar 

  16. Borhani-Haghighi M, Mohamadi Y (2019) The therapeutic effect of platelet-rich plasma on the experimental autoimmune encephalomyelitis mice. J Neuroimmunol 333:476958. https://doi.org/10.1016/j.jneuroim.2019.04.018

    Article  CAS  PubMed  Google Scholar 

  17. Anitua E, Pascual C, Perez-Gonzalez R, Orive G, Carro E (2015) Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-kappaB-dependent inflammation process in a mouse model of Parkinson’s disease. J Control Release 203:170–180. https://doi.org/10.1016/j.jconrel.2015.02.030

    Article  CAS  PubMed  Google Scholar 

  18. Yang J, Guo A, Li Q, Wu J (2021) Platelet-rich plasma attenuates interleukin-1beta-induced apoptosis and inflammation in chondrocytes through targeting hypoxia-inducible factor-2alpha. Tissue Cell 73:101646. https://doi.org/10.1016/j.tice.2021.101646

    Article  CAS  PubMed  Google Scholar 

  19. Park G, Qian W, Zhang MJ, Chen YH, Ma LW, Zeng N, Lu Q, Li YY, Ma WW, Yin XF, Zhou BR, Luo D (2021) Platelet-rich plasma regulating the repair of ultraviolet B-induced acute tissue inflammation: adjusting macrophage polarization through the activin receptor-follistatin system. Bioengineered 12:3125–3136. https://doi.org/10.1080/21655979.2021.1944026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dohan Ehrenfest DM, Rasmusson L, Albrektsson T (2009) Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends Biotechnol 27:158–167. https://doi.org/10.1016/j.tibtech.2008.11.009

    Article  CAS  PubMed  Google Scholar 

  21. Schindler MK, Forbes ME, Robbins ME, Riddle DR (2008) Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys 70:826–834. https://doi.org/10.1016/j.ijrobp.2007.10.054

    Article  PubMed  Google Scholar 

  22. Leger M, Quiedeville A, Bouet V, Haelewyn B, Boulouard M, Schumann-Bard P, Freret T (2013) Object recognition test in mice. Nat Protoc 8:2531–2537. https://doi.org/10.1038/nprot.2013.155

    Article  CAS  PubMed  Google Scholar 

  23. Gould TD, Dao DT, Kovacsics CE (2009) The Open Field Test. Neuromethods 83:1–20

    Google Scholar 

  24. Kraeuter AK, Guest PC, Sarnyai Z (2019) The elevated plus maze test for measuring anxiety-like Behavior in rodents. Methods Mol Biol 1916:69–74. https://doi.org/10.1007/978-1-4939-8994-2_4

    Article  CAS  PubMed  Google Scholar 

  25. Knight P, Chellian R, Wilson R, Behnood-Rod A, Panunzio S, Bruijnzeel AW (2021) Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats. Pharmacology, biochemistry, and behavior. 204:173168. https://doi.org/10.1016/j.pbb.2021.173168

  26. Bromley-Brits K, Deng Y, Song W (2011) Morris water maze test for learning and memory deficits in Alzheimer’s disease model mice. J Vis Exp 2920. https://doi.org/10.3791/2920

  27. Chen NF, Sung CS, Wen ZH, Chen CH, Feng CW, Hung HC, Yang SN, Tsui KH, Chen WF (2018) Therapeutic effect of platelet-rich plasma in rat spinal cord injuries. Front NeuroSci 12:252. https://doi.org/10.3389/fnins.2018.00252

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wei X, Jin XH, Meng XW, Hua J, Ji FH, Wang LN, Yang JP (2020) Platelet-rich plasma improves chronic inflammatory pain by inhibiting PKM2-mediated aerobic glycolysis in astrocytes. Annals of translational medicine 8(21):1456. https://doi.org/10.21037/atm-20-6502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Huang SH, Wu SH, Lee SS, Lin YN, Chai CY, Lai CS, Wang HD (2018) Platelet-Rich plasma injection in burn scar areas alleviates Neuropathic Scar Pain. Int J Med Sci 15(3):238–247. https://doi.org/10.7150/ijms.22563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z (2013) Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy 15(7):792–804. https://doi.org/10.1016/j.jcyt.2013.04.004

    Article  CAS  PubMed  Google Scholar 

  31. Bayat M, Khalili A, Bayat G, Akbari S, Yousefi Nejad A, Borhani Haghighi A, Haghani M (2022) Effects of platelet-rich plasma on the memory impairment, apoptosis, and hippocampal synaptic plasticity in a rat model of hepatic encephalopathy. Brain and behavior 12(1):e2447. https://doi.org/10.1002/brb3.2447

    Article  CAS  PubMed  Google Scholar 

  32. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS Statistical Report: primary brain and other Central Nervous System Tumors diagnosed in the United States in 2012–2016. Neuro Oncol 21:v1–v100. https://doi.org/10.1093/neuonc/noz150

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kim J, Lee S, Kang S, Kim SH, Kim JC, Yang M, Moon C (2017) Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration. Neural Regen Res 12(10):1733–1741. https://doi.org/10.4103/1673-5374.217353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Castro MV, Silva M, Chiarotto GB, Volpe BB, Santana MH, Malheiros Luzo AC, Oliveira ALR (2019) Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP). Brain Res Bull 152:212–224. https://doi.org/10.1016/j.brainresbull.2019.07.024

    Article  CAS  PubMed  Google Scholar 

  35. Ince B, Yildirim MEC, Kilinc I, Oltulu P, Dadaci M (2019) Investigation of the development of hypersensitivity and Hyperalgesia after repeated application of platelet-rich plasma in rats: an experimental study. Aesthet Surg J 39:1139–1145. https://doi.org/10.1093/asj/sjz113

    Article  PubMed  Google Scholar 

  36. Akeda K, Yamada J, Linn ET, Sudo A, Masuda K (2019) Platelet-rich plasma in the management of chronic low back pain: a critical review. J Pain Res 12:753–767. https://doi.org/10.2147/JPR.S153085

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tong S, Zhang C, Liu J (2017) Platelet-rich plasma exhibits beneficial effects for rheumatoid arthritis mice by suppressing inflammatory factors. Mol Med Rep 16:4082–4088. https://doi.org/10.3892/mmr.2017.7091

    Article  CAS  PubMed  Google Scholar 

  38. Monje ML, Mizumatsu S, Fike JR, Palmer TD (2002) Irradiation induces neural precursor-cell dysfunction. Nat Med 8:955–962. https://doi.org/10.1038/nm749

    Article  CAS  PubMed  Google Scholar 

  39. Acharya MM, Green KN, Allen BD, Najafi AR, Syage A, Minasyan H, Le MT, Kawashita T, Giedzinski E, Parihar VK, West BL, Baulch JE, Limoli CL (2016) Elimination of microglia improves cognitive function following cranial irradiation. Sci Rep 6:31545. https://doi.org/10.1038/srep31545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhao H, Wang M, Huang X, Wu X, Xiao H, Jin F, Lv J, Cheng J, Zhao Y, Zhang C (2022) Wasp venom from Vespa magnifica acts as a neuroprotective agent to alleviate neuronal damage after stroke in rats. Pharm Biol 60:334–346. https://doi.org/10.1080/13880209.2022.2032207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Houtman J, Freitag K, Gimber N, Schmoranzer J, Heppner FL, Jendrach M (2019) Beclin1-driven autophagy modulates the inflammatory response of microglia via NLRP3. EMBO J 38:e99430. https://doi.org/10.15252/embj.201899430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E (2018) Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov 17:588–606. https://doi.org/10.1038/nrd.2018.97

    Article  CAS  PubMed  Google Scholar 

  43. Qian J, Wang X, Su G, Shu X, Huang Z, Jiang H, Zhu Q (2022) Platelet-rich plasma-derived exosomes attenuate intervertebral disc degeneration by promoting NLRP3 autophagic degradation in macrophages. Int Immunopharmacol 110:108962. https://doi.org/10.1016/j.intimp.2022.108962

    Article  CAS  PubMed  Google Scholar 

  44. Zhu C, Chen L, Chen N, Ye Y, Lin D (2022) Dexmedetomidine ameliorates Morris Water Maze Learning in rats with postoperative cognitive dysfunction by enhancing Mitophagy and inhibiting the activation of the NLRP3 inflammasome. J Biol Regul Homeost Agents 36:1397–1407. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223605.150

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China

    Lu Ji

  2. Department of security, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China

    Rong-jie Jin

  3. Respiratory department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121000, China

    Lin Li

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  1. Lu Ji
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Lu Ji was responsible for project design and conducting experiments, Rong-jie Jin conducted experiments, data analysis and interpretation. Lin Li drafted the manuscript. All authors reviewed the manuscript.

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Ji, L., Jin, Rj. & Li, L. Platelet-rich Plasma Improves Radiotherapy-induced Emotional Disorder and Cognitive Dysfunction, Neuroinflammation in Aged Rats by Inhibiting the Activation of NLRP3 Inflammasomes. Neurochem Res 48, 2531–2541 (2023). https://doi.org/10.1007/s11064-023-03933-9

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