Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
August-2023 Volume 26 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2023 Volume 26 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats

  • Authors:
    • Masato Kobayashi
    • Nobuhiro Moro
    • Atsuo Yoshino
    • Takahiro Kumagawa
    • Katsunori Shijo
    • Takeshi Maeda
    • Hideki Oshima
  • View Affiliations / Copyright

    Affiliations: Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173‑8610, Japan
    Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 378
    |
    Published online on: June 23, 2023
       https://doi.org/10.3892/etm.2023.12077
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Release of large amounts of adenosine triphosphate (ATP), a gliotransmitter, into the extracellular space by traumatic brain injury (TBI) is considered to activate the microglia followed by release of inflammatory cytokines resulting in excessive inflammatory response that induces secondary brain injury. The present study investigated whether antagonists of ATP receptors (P2X4 and/or P2X7) on microglia are beneficial for reducing the post‑injury inflammatory response that leads to secondary injury, a prognostic aggravation factor of TBI. Adult male Sprague‑Dawley rats were subjected to cortical contusion injury (CCI) and randomly assigned to injury and drug treatment conditions, as follows: i) No surgical intervention (naïve group); ii) dimethyl sulfoxide treatment after CCI (CCI‑control group); iii) 5‑BDBD (antagonist of P2X4 receptor) treatment after CCI (CCI‑5‑BDBD group); iv) CCI‑AZ11645373 (antagonist of P2X7 receptor) treatment after CCI (CCI‑AZ11645373 group); v) or 5‑BDBD and AZ11645373 treatment after CCI (CCI‑5‑BDBD + AZ11645373 group). In the CCI‑5‑BDBD, CCI‑AZ11645373, and CCI‑5‑BDBD + AZ11645373 groups, expression of activated microglia was suppressed in the ipsilateral cortex and hippocampus 3 days after the CCI. Western blotting with ionized calcium‑binding adaptor molecule 1 antibody revealed that administration of CCI‑5‑BDBD and/or CCI‑AZ11645373 suppressed expression of microglia and reduced expression of inflammatory cytokine mRNA 3 days after the CCI. Furthermore, the plus maze test, which reflects the spatial memory function and involves the hippocampal function, showed improvement 28 days after secondary injury to the hippocampus. These findings confirmed that blocking the P2X4 and P2X7 receptors, which are ATP receptors central in gliotransmission, suppresses microglial activation and subsequent cytokine expression after brain injury, and demonstrates the potential as an effective treatment for reducing secondary brain injury.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML and Gan WB: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 8:752–758. 2005.PubMed/NCBI View Article : Google Scholar

2 

Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S and Inoue K: UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature. 446:1091–1095. 2007.PubMed/NCBI View Article : Google Scholar

3 

Wyatt SK, Witt T, Barbaro NM, Cohen-Gadol AA and Brewster AL: Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. 295:184–193. 2017.PubMed/NCBI View Article : Google Scholar

4 

Haydon PG and Carmignoto G: Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev. 86:1009–1031. 2006.PubMed/NCBI View Article : Google Scholar

5 

Cornell-Bell AH, Finkbeiner SM, Cooper MS and Smith SJ: Glutamate induces calcium waves in cultured astrocytes: Long-range glial signaling. Science. 247:470–473. 1990.PubMed/NCBI View Article : Google Scholar

6 

Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC and Kater SB: ATP released from astrocytes mediates glial calcium waves. J Neurosci. 19:520–528. 1999.PubMed/NCBI View Article : Google Scholar

7 

Taib T, Leconte C, Van Steenwinckel J, Cho AH, Palmier B, Torsello E, Lai Kuen R, Onyeomah S, Ecomard K, Benedetto C, et al: Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice. PLoS One. 12(e0184811)2017.PubMed/NCBI View Article : Google Scholar

8 

Miller WJ, Leventhal I, Scarsella D, Haydon PG, Janmey P and Meaney DF: Mechanically induced reactive gliosis causes ATP-mediated alterations in astrocyte stiffness. J Neurotrauma. 26:789–797. 2009.PubMed/NCBI View Article : Google Scholar

9 

Moro N, Ghavim SS and Sutton RL: Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain injury. Exp Ther Med. 21(575)2021.PubMed/NCBI View Article : Google Scholar

10 

Hua Y, Schallert T, Keep RF, Wu J, Hoff JT and Xi G: Behavioral tests after intracerebral hemorrhage in the rat. Stroke. 33:2478–2484. 2002.PubMed/NCBI View Article : Google Scholar

11 

Thelin EP, Frostell A, Mulder J, Mitsios N, Damberg P, Aski SN, Risling M, Svensson M, Morganti-Kossmann MC and Bellander BM: Lesion size is exacerbated in hypoxic rats whereas hypoxia-inducible factor-1 alpha and vascular endothelial growth factor increase in injured normoxic rats: A prospective cohort study of secondary hypoxia in focal traumatic brain injury. Front Neurol. 7(23)2016.PubMed/NCBI View Article : Google Scholar

12 

Xu L, He D and Bai Y: Microglia-mediated inflammation and neurodegenerative disease. Mol Neurobiol. 53:6709–6715. 2016.PubMed/NCBI View Article : Google Scholar

13 

Delekate A, Füchtemeier M, Schumacher T, Ulbrich C, Foddis M and Petzold GC: Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer's disease mouse model. Nat Commun. 5(5422)2014.PubMed/NCBI View Article : Google Scholar

14 

Choo AM, Miller WJ, Chen YC, Nibley P, Patel TP, Goletiani C, Morrison B III, Kutzing MK, Firestein BL, Sul JY, et al: Antagonism of purinergic signalling improves recovery from traumatic brain injury. Brain. 136:65–80. 2013.PubMed/NCBI View Article : Google Scholar

15 

Kumagawa T, Moro N, Maeda T, Kobayashi M, Furukawa Y, Shijo K and Yoshino A: Anti-inflammatory effect of P2Y1 receptor blocker MRS2179 in a rat model of traumatic brain injury. Brain Res Bull. 181:46–54. 2022.PubMed/NCBI View Article : Google Scholar

16 

Filiano AJ, Gadani SP and Kipnis J: Interactions of innate and adaptive immunity in brain development and function. Brain Res. 1617:18–27. 2015.PubMed/NCBI View Article : Google Scholar

17 

Sordillo PP, Sordillo LA and Helson L: Bifunctional role of pro-inflammatory cytokines after traumatic brain injury. Brain Inj. 30:1043–1053. 2016.PubMed/NCBI View Article : Google Scholar

18 

Moro N, Ghavim SS, Harris NG, Hovda DA and Sutton RL: Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury. Brain Res. 1642:270–277. 2016.PubMed/NCBI View Article : Google Scholar

19 

Goodman JC, Cherian L, Bryan RM Jr and Robertson CS: Lateral cortical impact injury in rats: Pathologic effects of varying cortical compression and impact velocity. J Neurotrauma. 11:587–597. 1994.PubMed/NCBI View Article : Google Scholar

20 

Dalgard CL, Cole JT, Kean WS, Lucky JJ, Sukumar G, McMullen DC, Pollard HB and Watson WD: The cytokine temporal profile in rat cortex after controlled cortical impact. Front Mol Neurosci. 5(6)2012.PubMed/NCBI View Article : Google Scholar

21 

Sofroniew MV and Vinters HV: Astrocytes: Biology and pathology. Acta Neuropathol. 119:7–35. 2010.PubMed/NCBI View Article : Google Scholar

22 

Zhang L, Schallert T, Zhang ZG, Jiang Q, Arniego P, Li Q, Lu M and Chopp M: A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia. J Neurosci Methods. 117:207–214. 2002.PubMed/NCBI View Article : Google Scholar

23 

Gharbawie OA, Whishaw PA and Whishaw IQ: The topography of three-dimensional exploration: A new quantification of vertical and horizontal exploration, postural support, and exploratory bouts in the cylinder test. Behav Brain Res. 151:125–135. 2004.PubMed/NCBI View Article : Google Scholar

24 

Chao OY, Pum ME, Li JS and Huston JP: The grid-walking test: Assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle. Neuroscience. 202:318–325. 2012.PubMed/NCBI View Article : Google Scholar

25 

McNay EC, Fries TM and Gold PE: Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task. Proc Natl Acad Sci USA. 97:2881–2885. 2000.PubMed/NCBI View Article : Google Scholar

26 

Taylor AN, Rahman SU, Sanders NC, Tio DL, Prolo P and Sutton RL: Injury severity differentially affects short- and long-term neuroendocrine outcomes of traumatic brain injury. J Neurotrauma. 25:311–323. 2008.PubMed/NCBI View Article : Google Scholar

27 

Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA and Mullan M: Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Science. 286:2352–2355. 1999.PubMed/NCBI View Article : Google Scholar

28 

Faroqi AH, Lim MJ, Kee EC, Lee JH, Burgess JD, Chen R, Di Virgilio F, Delenclos M and McLean PJ: In vivo detection of extracellular adenosine triphosphate in a mouse model of traumatic brain injury. J Neurotrauma. 38:655–664. 2021.PubMed/NCBI View Article : Google Scholar

29 

Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M and Pedata F: ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int. 47:442–448. 2005.PubMed/NCBI View Article : Google Scholar

30 

Peng J, Liu Y, Umpierre AD, Xie M, Tian DS, Richardson JR and Wu LJ: Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice. Mol Brain. 12(71)2019.PubMed/NCBI View Article : Google Scholar

31 

Abiega O, Beccari S, Diaz-Aparicio I, Nadjar A, Layé S, Leyrolle Q, Gómez-Nicola D, Domercq M, Pérez-Samartín A, Sánchez-Zafra V, 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.PubMed/NCBI View Article : Google Scholar

32 

Trapp BD, Bö L, Mörk S and Chang A: Pathogenesis of tissue injury in MS lesions. J Neuroimmunol. 98:49–56. 1999.PubMed/NCBI View Article : Google Scholar

33 

Aboud O, Mrak RE, Boop F and Griffin ST: Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience. BMC Med. 10(35)2012.PubMed/NCBI View Article : Google Scholar

34 

Osipova ED, Semyachkina-Glushkovskaya OV, Morgun AV, Pisareva NV, Malinovskaya NA, Boitsova EB, Pozhilenkova EA, Belova OA, Salmin VV, Taranushenko TE, et al: Gliotransmitters and cytokines in the control of blood-brain barrier permeability. Rev Neurosci. 29:567–591. 2018.PubMed/NCBI View Article : Google Scholar

35 

Perez-Polo JR, Rea HC, Johnson KM, Parsley MA, Unabia GC, Xu GY, Prough D, DeWitt DS, Paulucci-Holthauzen AA, Werrbach-Perez K and Hulsebosch CE: Inflammatory cytokine receptor blockade in a rodent model of mild traumatic brain injury. J Neurosci Res. 94:27–38. 2016.PubMed/NCBI View Article : Google Scholar

36 

Jassam YN, Izzy S, Whalen M, McGavern DB and El Khoury J: Neuroimmunology of traumatic brain injury: Time for a paradigm shift. Neuron. 95:1246–1265. 2017.PubMed/NCBI View Article : Google Scholar

37 

Xu H, Wang Z, Li J, Wu H, Peng Y, Fan L, Chen J, Gu C, Yan F, Wang L and Chen G: The polarization states of microglia in TBI: A new paradigm for pharmacological intervention. Neural Plast. 2017(5405104)2017.PubMed/NCBI View Article : Google Scholar

38 

Menzel L, Kleber L, Friedrich C, Hummel R, Dangel L, Winter J, Schmitz K, Tegeder I and Schäfer MK: Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury. Glia. 65:278–292. 2017.PubMed/NCBI View Article : Google Scholar

39 

Nikolic L, Shen W, Nobili P, Virenque A, Ulmann L and Audinat E: Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis. Glia. 66:2673–2683. 2018.PubMed/NCBI View Article : Google Scholar

40 

Silver J and Miller JH: Regeneration beyond the glial scar. Nat Rev Neurosci. 5:146–156. 2004.PubMed/NCBI View Article : Google Scholar

41 

Kaiser M, Penk A, Franke H, Krügel U, Nörenberg W, Huster D and Schaefer M: Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion. Purinergic Signal. 12:453–463. 2016.PubMed/NCBI View Article : Google Scholar

42 

Ekmark-Lewén S, Flygt J, Fridgeirsdottir GA, Kiwanuka O, Hånell A, Meyerson BJ, Mir AK, Gram H, Lewén A, Clausen F, et al: Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β. Eur J Neurosci. 43:1016–1033. 2016.PubMed/NCBI View Article : Google Scholar

43 

Helmy A, Guilfoyle MR, Carpenter KLH, Pickard JD, Menon DK and Hutchinson PJ: Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury. J Cereb Blood Flow Metab. 36:1434–1448. 2016.PubMed/NCBI View Article : Google Scholar

44 

Fehily B and Fitzgerald M: Repeated mild traumatic brain injury: Potential mechanisms of damage. Cell Transplant. 26:1131–1155. 2017.PubMed/NCBI View Article : Google Scholar

45 

Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA and Murphy TH: Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci. 23:3394–3406. 2003.PubMed/NCBI View Article : Google Scholar

46 

Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH and Sofroniew MV: Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 23:297–308. 1999.PubMed/NCBI View Article : Google Scholar

47 

Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP and Welty DF: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron. 16:675–686. 1996.PubMed/NCBI View Article : Google Scholar

48 

Li L, Lundkvist A, Andersson D, Wilhelmsson U, Nagai N, Pardo AC, Nodin C, Ståhlberg A, Aprico K, Larsson K, et al: Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab. 28:468–481. 2008.PubMed/NCBI View Article : Google Scholar

49 

Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, Yamane J, Yoshimura A, Iwamoto Y, Toyama Y and Okano H: Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med. 12:829–834. 2006.PubMed/NCBI View Article : Google Scholar

50 

Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S and Sofroniew MV: Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci. 29:11511–11522. 2009.PubMed/NCBI View Article : Google Scholar

51 

Oberheim NA, Tian GF, Han X, Peng W, Takano T, Ransom B and Nedergaard M: Loss of astrocytic domain organization in the epileptic brain. J Neurosci. 28:3264–3276. 2008.PubMed/NCBI View Article : Google Scholar

52 

Norden DM, Trojanowski PJ, Villanueva E, Navarro E and Godbout JP: Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. 64:300–316. 2016.PubMed/NCBI View Article : Google Scholar

53 

Scherbel U, Raghupathi R, Nakamura M, Saatman KE, Trojanowski JQ, Neugebauer E, Marino MW and McIntosh TK: Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci USA. 96:8721–8726. 1999.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kobayashi M, Moro N, Yoshino A, Kumagawa T, Shijo K, Maeda T and Oshima H: Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats. Exp Ther Med 26: 378, 2023.
APA
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., & Oshima, H. (2023). Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats. Experimental and Therapeutic Medicine, 26, 378. https://doi.org/10.3892/etm.2023.12077
MLA
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., Oshima, H."Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats". Experimental and Therapeutic Medicine 26.2 (2023): 378.
Chicago
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., Oshima, H."Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats". Experimental and Therapeutic Medicine 26, no. 2 (2023): 378. https://doi.org/10.3892/etm.2023.12077
Copy and paste a formatted citation
x
Spandidos Publications style
Kobayashi M, Moro N, Yoshino A, Kumagawa T, Shijo K, Maeda T and Oshima H: Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats. Exp Ther Med 26: 378, 2023.
APA
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., & Oshima, H. (2023). Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats. Experimental and Therapeutic Medicine, 26, 378. https://doi.org/10.3892/etm.2023.12077
MLA
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., Oshima, H."Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats". Experimental and Therapeutic Medicine 26.2 (2023): 378.
Chicago
Kobayashi, M., Moro, N., Yoshino, A., Kumagawa, T., Shijo, K., Maeda, T., Oshima, H."Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats". Experimental and Therapeutic Medicine 26, no. 2 (2023): 378. https://doi.org/10.3892/etm.2023.12077
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team