DOI QR코드

DOI QR Code

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model

  • Gokhan Gurkan (Department of Neurosurgery, Izmir Katip Celebi University Ataturk Training and Research Hospital) ;
  • Ozum Atasoy (Department of Radiation Oncology, Kartal City Hospital) ;
  • Nilsu Cini (Department of Radiation Oncology, Kartal City Hospital) ;
  • Ibrahim Halil Sever (Department of Radiology, Demiroglu Bilim University) ;
  • Bahattin Ozkul (Department of Radiology, Istanbul Atlas University) ;
  • Gokhan Yaprak (Department of Radiation Oncology, Lutfi Kirdar Kartal Education and Research Hospital) ;
  • Cansin Sirin (Department of Histology and Embryology, Faculty of Medicine, Ege University) ;
  • Yigit Uyanikgil (Department of Histology and Embryology, Faculty of Medicine, Ege University) ;
  • Ceren Kizmazoglu (Department of Neurosurgery, Faculty of Medicine, Dokuz Eylul University) ;
  • Mumin Alper Erdogan (Department of Physiology, Katip Celebi University) ;
  • Oytun Erbas (Department of Physiology, Demiroglu Bilim University)
  • 투고 : 2023.03.07
  • 심사 : 2023.04.24
  • 발행 : 2023.09.01

초록

Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

키워드

참고문헌

  1. Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, et al. : Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury. PLoS One 9 : e90953, 2014
  2. Albensi BC : What is nuclear factor kappa B (NF-κB) doing in and to the mitochondrion? Front Cell Dev Biol 7 : 154, 2019
  3. Bajwa NM, Halavi S, Hamer M, Semple BD, Noble-Haeusslein LJ, Baghchechi M, et al. : Mild concussion, but not moderate traumatic brain injury, is associated with long-term depression-like phenotype in mice. PLoS One 11 : e0146886, 2016
  4. Bathina S, Das UN : Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 11 : 1164-1178, 2015 https://doi.org/10.5114/aoms.2015.56342
  5. Broussard JI, Redell JB, Zhao J, Maynard ME, Kobori N, Perez A, et al. : Mild traumatic brain injury decreases spatial information content and reduces place field stability of hippocampal CA1 neurons. J Neurotrauma 37 : 227-235, 2020 https://doi.org/10.1089/neu.2019.6766
  6. Carpenter KL, Jalloh I, Hutchinson PJ : Glycolysis and the significance of lactate in traumatic brain injury. Front Neurosci 9 : 112, 2015
  7. Dela Pena I, Sanberg PR, Acosta S, Tajiri N, Lin SZ, Borlongan CV : Stem cells and G-CSF for treating neuroinflammation in traumatic brain injury: aging as a comorbidity factor. J Neurosurg Sci 58 : 145-149, 2014
  8. Dumbuya JS, Chen L, Wu JY, Wang B : The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status. J Neuroinflammation 18 : 55, 2021
  9. Eakin K, Miller JP : Mild traumatic brain injury is associated with impaired hippocampal spatiotemporal representation in the absence of histological changes. J Neurotrauma 29 : 1180-1187, 2012 https://doi.org/10.1089/neu.2011.2192
  10. Erbas O, Erdogan MA, Khalilnezhad A, Gurkan FT, Yigitturk G, Meral A, et al. : Neurobehavioral effects of long-term maternal fructose intake in rat offspring. Int J Dev Neurosci 69 : 68-79, 2018 https://doi.org/10.1016/j.ijdevneu.2018.07.001
  11. Goshen INBAL, Yirmiya R : The role of pro-inflammatory cytokines in memory processes and neural plasticity. Psychoneuroimmunology 4 : 337-378, 2007 https://doi.org/10.1016/B978-012088576-3/50021-6
  12. Horakova L, Ondrejickova O, Bachrata K, Vajdova M : Preventive effect of several antioxidants after oxidative stress on rat brain homogenates. Gen Physiol Biophys 19 : 195-206, 2000
  13. Izci Y, Erbas YC : Hipokampus: yapisi ve fonksiyonlari. Turk Norosir Derg 25 : 287-295, 2015
  14. Kerman M, Cirak B, Ozguner MF, Dagtekin A, Sutcu R, Altuntas I, et al. : Does melatonin protect or treat brain damage from traumatic oxidative stress? Exp Brain Res 163 : 406-410, 2005 https://doi.org/10.1007/s00221-005-2338-2
  15. Li H, Linjuan-Li, Wang Y : G-CSF improves CUMS-induced depressive behaviors through downregulating Ras/ERK/MAPK signaling pathway. Biochem Biophys Res Commun 479 : 827-832, 2016 https://doi.org/10.1016/j.bbrc.2016.09.123
  16. Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, et al. : Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25 : 1481-1488, 1994 https://doi.org/10.1161/01.STR.25.7.1481
  17. Meral R : Radyasyonun bilissel fonksiyonlara etkisi. Turk Norosirurji Dergisi 17 : 139-148, 2007
  18. Moy SS, Nadler JJ, Young NB, Nonneman RJ, Segall SK, Andrade GM, et al. : Social approach and repetitive behavior in eleven inbred mouse strains. Behav Brain Res 191 : 118-129, 2008 https://doi.org/10.1016/j.bbr.2008.03.015
  19. Nadler JJ, Moy SS, Dold G, Trang D, Simmons N, Perez A, et al. : Automated apparatus for quantitation of social approach behaviors in mice. Genes Brain Behav 3 : 303-314, 2004 https://doi.org/10.1111/j.1601-183X.2004.00071.x
  20. Nolan A, Hennessy E, Krukowski K, Guglielmetti C, Chaumeil MM, Sohal VS, et al. : Repeated mild head injury leads to wide-ranging deficits in higher-order cognitive functions associated with the prefrontal cortex. J Neurotrauma 35 : 2425-2434, 2018 https://doi.org/10.1089/neu.2018.5731
  21. Paolin A, Nardin L, Gaetani P, Rodriguez Y Baena R, Pansarasa O, Marzatico F : Oxidative damage after severe head injury and its relationship to neurological outcome. Neurosurgery 51 : 949-954; discussion 954-955, 2002
  22. Park CH, Joa KL, Lee MO, Yoon SH, Kim MO : The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury. J Spinal Cord Med 43 : 339-346, 2020 https://doi.org/10.1080/10790268.2018.1521567
  23. Pendergrass JC, Targum SD, Harrison JE : Cognitive impairment associated with cancer: a brief review. Innov Clin Neurosci 15 : 36-44, 2018
  24. Rahman R, Sulman E, Haas-Kogan D, Cagney DN : Update on radiation therapy for central nervous system tumors. Hematol Oncol Clin North Am 36 : 77-93, 2022 https://doi.org/10.1016/j.hoc.2021.08.006
  25. Rowland LM, Pradhan S, Korenic S, Wijtenburg SA, Hong LE, Edden RA, et al. : Elevated brain lactate in schizophrenia: a 7T magnetic resonance spectroscopy study. Transl Psychiatry 6 : e967, 2016
  26. Salberg S, Yamakawa G, Christensen J, Kolb B, Mychasiuk R : Assessment of a nutritional supplement containing resveratrol, prebiotic fiber, and omega-3 fatty acids for the prevention and treatment of mild traumatic brain injury in rats. Neuroscience 365 : 146-157, 2017 https://doi.org/10.1016/j.neuroscience.2017.09.053
  27. Schneider A, Kruger C, Steigleder T, Weber D, Pitzer C, Laage R, et al. The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 115 : 2083-2098, 2005 https://doi.org/10.1172/JCI23559
  28. Scorza CA, Marques MJG, Gomes da Silva S, Naffah-Mazzacoratti MDG, Scorza FA, Cavalheiro EA : Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis. Neurosci Lett 668 : 169-173, 2018 https://doi.org/10.1016/j.neulet.2017.02.049
  29. Shibamoto Y : Radiation therapy for primary central nervous system lymphoma. Oncol Rev 7 : e4, 2013
  30. Shih RH, Wang CY, Yang CM : NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci 8 : 77, 2015
  31. Shyu WC, Lin SZ, Lee CC, Liu DD, Li H : Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. CMAJ 174 : 927-933, 2006 https://doi.org/10.1503/cmaj.051322
  32. Sikoglu EM, Heffernan ME, Tam K, Sicard KM, Bratane BT, Quan M, et al. : Enhancement in cognitive function recovery by granulocyte-colony stimulating factor in a rodent model of traumatic brain injury. Behav Brain Res 259 : 354-356, 2014
  33. Solaroglu I, Cahill J, Jadhav V, Zhang JH : A novel neuroprotectant granulocyte-colony stimulating factor. Stroke 37 : 1123-1128, 2006 https://doi.org/10.1161/01.STR.0000208205.26253.96
  34. Solmaz V, Erdogan MA, Alnak A, Meral A, Erbas O : Erythropoietin shows gender dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide induced rat model of autism. Neuropeptides 83 : 102073, 2020
  35. Song S, Kong X, Acosta S, Sava V, Borlongan C, Sanchez-Ramos J : Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury. J Neurosci Res 94 : 409-423, 2016 https://doi.org/10.1002/jnr.23714
  36. Tan XL, Wright DK, Liu S, Hovens C, O'Brien TJ, Shultz SR : Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes. Neuropharmacology 108 : 382-393, 2016 https://doi.org/10.1016/j.neuropharm.2016.05.001
  37. Taphoorn MJ, Klein M : Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3 : 159-168, 2004 https://doi.org/10.1016/S1474-4422(04)00680-5
  38. Warner DS, Sheng H, Batinic-Haberle I : Oxidants, antioxidants and the ischemic brain. J Exp Biol 207(Pt 18) : 3221-3231, 2004 https://doi.org/10.1242/jeb.01022
  39. Yagmur EN, Yildiz N, Adiguzel S, Femir B, Senyer S, Sen M, et al. : The role of NF-κb in neuronal plasticity and neurodegenerative diseases. Deneysel Tip Arastirma Enstitusu Dergisi 7 : 71-85, 2017
  40. Yang DY, Chen YJ, Wang MF, Pan HC, Chen SY, Cheng FC : Granulocyte colony-stimulating factor enhances cellular proliferation and motor function recovery on rats subjected to traumatic brain injury. Neurol Res 32 : 1041-1049, 2010 https://doi.org/10.1179/016164110X12807570510013
  41. Yang Z, Wang KK : Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci 38 : 364-374, 2015 https://doi.org/10.1016/j.tins.2015.04.003