Skip to main content

Advertisement

SpringerLink
Log in

Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus

  • Original Paper
  • Published:
Child's Nervous System Aims and scope Submit manuscript

Abstract

Purpose

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus.

Methods

Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies.

Results

The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group.

Conclusions

We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Del Bigio MR, Bruni JE, Fewer HD (1985) Human neonatal hydrocephalus. An electron microscopic study of the periventricular tissue. J Neurosurg 63:56–63

    Article  CAS  PubMed  Google Scholar 

  2. Yamada S, Kelly E (2016) Cerebrospinal fluid dynamics and the pathophysiology of hydrocephalus: new concepts. Semin Ultrasound CT MR 37:84–91

    Article  PubMed  Google Scholar 

  3. Socci DJ, Bjugstad KB, Jones HC, Pattisapu JV, Arendash GW (1999) Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Exp Neurol 155:109–117

    Article  CAS  PubMed  Google Scholar 

  4. Cosan TE, Gucuyener D, Dundar E, Arslantas A, Vural M, Uzuner K, Tel E (2001) Cerebral blood flow alterations in progressive communicating hydrocephalus: transcranial Doppler ultrasonography assessment in an experimental model. J Neurosurg 94:265–269

    Article  CAS  PubMed  Google Scholar 

  5. Higashi K, Asahisa H, Ueda N, Kobayashi K, Hara K, Noda Y (1986) Cerebral blood flow and metabolism in experimental hydrocephalus. Neurol Res 8:169–176

    Article  CAS  PubMed  Google Scholar 

  6. da Silva MC, Michowicz S, Drake JM, Chumas PD, Tuor UI (1995) Reduced local cerebral blood flow in periventricular white matter in experimental neonatal hydrocephalus-restoration with CSF shunting. J Cereb Blood Flow Metab 15:1057–1065

    Article  PubMed  Google Scholar 

  7. Shulyakov AV, Buist RJ, Del Bigio MR (2012) Intracranial biomechanics of acute experimental hydrocephalus in live rats. Neurosurgery 71:1032–1040

    Article  PubMed  Google Scholar 

  8. Caner H, Atasever A, Kilinc K, Durgun B, Peker S, Ozcan OE (1993) Lipid peroxide level increase in experimental hydrocephalus. Acta Neurochir 121:68–71

    Article  CAS  PubMed  Google Scholar 

  9. Fersten E, Gordon-Krajcer W, Glowacki M, Mroziak B, Jurkiewicz J, Czernicki Z (2004) Cerebrospinal fluid free-radical peroxidation products and cognitive functioning patterns differentiate varieties of normal pressure hydrocephalus. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences 42:133–140

    CAS  Google Scholar 

  10. Thiong'o GM, Luzzio C, Albright AL (2015) Ventriculoperitoneal shunt perforations of the gastrointestinal tract. J Neurosurg Pediatr: 1–6

  11. Jones HM, Hussain R, Leach P (2015) Patient dependant on ventriculo-atrial shunt after 49 years. Br J Neurosurg: 1–2

  12. Boon AJ, Tans JT, Delwel EJ, Egeler-Peerdeman SM, Hanlo PW, Wurzer HA, Hermans J (1999) Dutch normal-pressure hydrocephalus study: the role of cerebrovascular disease. J Neurosurg 90:221–226

    Article  CAS  PubMed  Google Scholar 

  13. White IK, Shaikh KA, Nyarenchi OM, Kundu MG, Boaz JC, Fulkerson DH (2015) Analysis of the potential risk of central intravenous lines and/or total parenteral nutrition with ventriculoatrial shunts. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 31:563–568

    Article  Google Scholar 

  14. Simon TD, Hall M, Riva-Cambrin J, Albert JE, Jeffries HE, Lafleur B, Dean JM, Kestle JR (2009) Infection rates following initial cerebrospinal fluid shunt placement across pediatric hospitals in the United States. Clinical article. J Neurosurg Pediatr 4:156–165

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ochieng N, Okechi H, Ferson S, Albright AL (2015) Bacteria causing ventriculoperitoneal shunt infections in a Kenyan population. J Neurosurg Pediatr 15:150–155

    Article  PubMed  Google Scholar 

  16. Catalao CH, Correa DA, Saito ST, Lopes Lda S (2014) Camellia sinensis neuroprotective role in experimentally induced hydrocephalus in Wistar rats. Childs Nerv Syst 30:591–597

    Article  PubMed  Google Scholar 

  17. Ishibashi A, Yoshitake Y, Adachi H (2013) Investigation of effect of edaravone on ischemic stroke. The Kurume medical journal 60:53–57

    Article  CAS  PubMed  Google Scholar 

  18. Dohare P, Hyzinski-Garcia MC, Vipani A, Bowens NH, Nalwalk JW, Feustel PJ, Keller RW, Jr., Jourd'heuil D, Mongin AA (2014) The neuroprotective properties of the superoxide dismutase mimetic tempol correlate with its ability to reduce pathological glutamate release in a rodent model of stroke. Free Radic Biol Med

  19. Kikuchi K, Miura N, Kawahara KI, Murai Y, Morioka M, Lapchak PA, Tanaka E (2013) Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke. Biomedical reports 1:7–12

    CAS  PubMed  Google Scholar 

  20. Nakamura T, Kuroda Y, Yamashita S, Zhang X, Miyamoto O, Tamiya T, Nagao S, Xi G, Keep RF, Itano T (2008) Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke 39:463–469

    Article  CAS  PubMed  Google Scholar 

  21. Noor JI, Ikeda T, Mishima K, Aoo N, Ohta S, Egashira N, Iwasaki K, Fujiwara M, Ikenoue T (2005) Short-term administration of a new free radical scavenger, edaravone, is more effective than its long-term administration for the treatment of neonatal hypoxic-ischemic encephalopathy. Stroke 36:2468–2474

    Article  CAS  PubMed  Google Scholar 

  22. Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, Nagahiro S (2009) Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke 40:626–631

    Article  CAS  PubMed  Google Scholar 

  23. Munakata A, Ohkuma H, Nakano T, Shimamura N, Asano K, Naraoka M (2009) Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 64:423–428 discussion 428-429

    Article  PubMed  Google Scholar 

  24. Ito H, Wate R, Zhang J, Ohnishi S, Kaneko S, Nakano S, Kusaka H (2008) Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Exp Neurol 213:448–455

    Article  CAS  PubMed  Google Scholar 

  25. Itoh T, Satou T, Nishida S, Tsubaki M, Hashimoto S, Ito H (2009) The novel free radical scavenger, edaravone, increases neural stem cell number around the area of damage following rat traumatic brain injury. Neurotox Res 16:378–389

    Article  CAS  PubMed  Google Scholar 

  26. Wang J, Guo G, Wang W, Tang Y, Shun J, Zhou X, Zhang P (2013) Effect of methylprednisolone and edaravone administration on spinal cord injury. Eur Rev Med Pharmacol Sci 17:2766–2772

    CAS  PubMed  Google Scholar 

  27. Kamida T, Fujiki M, Ooba H, Anan M, Abe T, Kobayashi H (2009) Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus. Seizure 18:71–75

    Article  CAS  PubMed  Google Scholar 

  28. Lopes Lda S, Slobodian I, Del Bigio MR (2009) Characterization of juvenile and young adult mice following induction of hydrocephalus with kaolin. Exp Neurol 219:187–196

    Article  PubMed  Google Scholar 

  29. Kamida T, Abe E, Abe T, Ooba H, Fujiki M, Kobayashi H (2009) Edaravone, a free radical scavenger, retards the development of amygdala kindling in rats. Neurosci Lett 461:298–301

    Article  CAS  PubMed  Google Scholar 

  30. Rocha Catalao CH, Leme Correa DA, Bernardino Garcia CA, Dos Santos AC, Garrido Salmon CE, Alves Rocha MJ, da Silva Lopes L (2014) Pre- and postshunting magnetization transfer ratios are in accordance with neurological and behavioral changes in hydrocephalic immature rats. Dev Neurosci 36:520–531

    Article  CAS  PubMed  Google Scholar 

  31. Fox WM (1965) Reflex-ontogeny and behavioural development of the mouse. Anim Behav 13:234–241

    Article  CAS  PubMed  Google Scholar 

  32. Khan OH, Enno TL, Del Bigio MR (2006) Brain damage in neonatal rats following kaolin induction of hydrocephalus. Exp Neurol 200:311–320

    Article  CAS  PubMed  Google Scholar 

  33. Tatem KS, Quinn JL, Phadke A, Yu Q, Gordish-Dressman H, Nagaraju K (2014) Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases. J Vis Exp: JoVE

  34. Williams MT, Braun AA, Amos-Kroohs RM, McAllister JP, Lindquist DM, Mangano FT, Vorhees CV, Yuan W (2014) Kaolin-induced ventriculomegaly at weaning produces long-term learning, memory, and motor deficits in rats. Int J Dev Neurosci 35:7–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Braun KP, Dijkhuizen RM, de Graaf RA, Nicolay K, Vandertop WP, Gooskens RH, Tulleken KA (1997) Cerebral ischemia and white matter edema in experimental hydrocephalus: a combined in vivo MRI and MRS study. Brain Res 757:295–298

    Article  CAS  PubMed  Google Scholar 

  36. Castro SC, Machado HR, Catalao CH, Siqueira BA, Simoes AL, Lachat JJ, Lopes Lda S (2012) 0.1 T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size. Acta Cir Bras 27:768–772

    Article  PubMed  Google Scholar 

  37. Corkill RG, Garnett MR, Blamire AM, Rajagopalan B, Cadoux-Hudson TA, Styles P (2003) Multi-modal MRI in normal pressure hydrocephalus identifies pre-operative haemodynamic and diffusion coefficient changes in normal appearing white matter correlating with surgical outcome. Clin Neurol Neurosurg 105:193–202

    Article  PubMed  Google Scholar 

  38. Yamada H, Yokota A, Furuta A, Horie A (1992) Reconstitution of shunted mantle in experimental hydrocephalus. J Neurosurg 76:856–862

    Article  CAS  PubMed  Google Scholar 

  39. Yuan W, Mangano FT, Air EL, Holland SK, Jones BV, Altaye M, Bierbrauer K (2009) Anisotropic diffusion properties in infants with hydrocephalus: a diffusion tensor imaging study. AJNR Am J Neuroradiol 30:1792–1798

    Article  CAS  PubMed  Google Scholar 

  40. Newbould RD, Nicholas R, Thomas CL, Quest R, Lee JS, Honeyfield L, Colasanti A, Malik O, Mattoscio M, Matthews PM, Sormani MP, Waldman AD, Muraro PA (2014) Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis. NeuroImage Clinical 4:641–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schmierer K, Wheeler-Kingshott CA, Tozer DJ, Boulby PA, Parkes HG, Yousry TA, Scaravilli F, Barker GJ, Tofts PS, Miller DH (2008) Quantitative magnetic resonance of postmortem multiple sclerosis brain before and after fixation. Magn Reson Med 59:268–277

    Article  PubMed  PubMed Central  Google Scholar 

  42. Levesque I, Sled JG, Narayanan S, Santos AC, Brass SD, Francis SJ, Arnold DL, Pike GB (2005) The role of edema and demyelination in chronic T1 black holes: a quantitative magnetization transfer study. J Magn Reson Imaging 21:103–110

    Article  PubMed  Google Scholar 

  43. Giacomini PS, Levesque IR, Ribeiro L, Narayanan S, Francis SJ, Pike GB, Arnold DL (2009) Measuring demyelination and remyelination in acute multiple sclerosis lesion voxels. Arch Neurol 66:375–381

    PubMed  Google Scholar 

  44. Silver NC, Barker GJ, MacManus DG, Tofts PS, Miller DH (1997) Magnetisation transfer ratio of normal brain white matter: a normative database spanning four decades of life. J Neurol Neurosurg Psychiatry 62:223–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sled JG, Levesque I, Santos AC, Francis SJ, Narayanan S, Brass SD, Arnold DL, Pike GB (2004) Regional variations in normal brain shown by quantitative magnetization transfer imaging. Magn Reson Med 51:299–303

    Article  CAS  PubMed  Google Scholar 

  46. Wang GH, Jiang ZL, Li YC, Li X, Shi H, Gao YQ, Vosler PS, Chen J (2011) Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats. J Neurotrauma 28:2123–2134

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ishikawa A, Yoshida H, Metoki N, Toki T, Imaizumi T, Matsumiya T, Yamashita K, Taima K, Satoh K (2007) Edaravone inhibits the expression of vascular endothelial growth factor in human astrocytes exposed to hypoxia. Neurosci Res 59:406–412

    Article  CAS  PubMed  Google Scholar 

  48. Botfield H, Gonzalez AM, Abdullah O, Skjolding AD, Berry M, McAllister JP, Logan A (2013) Decorin prevents the development of juvenile communicating hydrocephalus. Brain 136:2842–2858

    Article  PubMed  Google Scholar 

  49. Xu H, Tan G, Zhang S, Zhu H, Liu F, Huang C, Zhang F, Wang Z (2012) Minocycline reduces reactive gliosis in the rat model of hydrocephalus. BMC Neurosci 13:148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Di Curzio DL, Turner-Brannen E, Mao X, Del Bigio MR (2016) Magnesium sulfate treatment for juvenile ferrets following induction of hydrocephalus with kaolin. Fluids Barriers CNS 13:7

    Article  PubMed  PubMed Central  Google Scholar 

  51. Li X, Li L, Li J, Sipple J, Schick J, Mehta PA, Davies SM, Dasgupta B, Waclaw RR, Pang Q (2014) Concomitant inactivation of foxo3a and fancc or fancd2 reveals a two-tier protection from oxidative stress-induced hydrocephalus. Antioxid Redox Signal

  52. Di Curzio DL, Turner-Brannen E, Del Bigio MR (2014) Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus. Fluids Barriers CNS 11:23

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N (2006) Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev 12:9–20

    Article  CAS  PubMed  Google Scholar 

  54. Li Q, Bi MJ, Bi WK, Kang H, Yan LJ, Guo YL (2014) Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress. Environ Toxicol

  55. Tsuruoka A, Atsumi C, Mizukami H, Imai T, Hagiwara Y, Hasegawa Y (2014) Effects of edaravone, a free radical scavenger, on circulating levels of MMP-9 and hemorrhagic transformation in patients with intravenous thrombolysis using low-dose alteplase. J Stroke Cerebrovasc Dis

  56. Shokrzadeh M, Shaki F, Mohammadi E, Rezagholizadeh N, Ebrahimi F (2014) Edaravone decreases paraquat toxicity in a549 cells and lung isolated mitochondria. Iran J Pharm Res 13:675–681

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was funded by a grant and regulates assistance from FAPESP—Foundation of São Paulo Research. Camila A B Garcia was a recipient of FAPESP scholarship (grant number 2013/04130-6). The authors are grateful to Antonio Renato Meirelles e Silva for his assistance with the microscope photographs and to Prof Dr. João Pereira Leite for his assistance with the immunofluorescence analysis (Department of Neuroscience and Behavioral Sciences, Faculty of Medicine of Ribeirão Preto, University of São Paulo).

Author information

Authors and Affiliations

  1. Department of Surgery and Anatomy, Division of Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, 3900 Av. dos Bandeirantes, Ribeirao Preto, SP, 14049-900, Brazil

    Camila Araújo Bernardino Garcia, Hélio Rubens Machado, Ivair Matias Júnior, Thais Helena Romeiro, Marcelo Volpon Santos & Luiza da Silva Lopes

  2. Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil

    Carlos Henrique Rocha Catalão & José Eduardo Peixoto-Santos

Authors
  1. Camila Araújo Bernardino Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Henrique Rocha Catalão
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hélio Rubens Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivair Matias Júnior
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thais Helena Romeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José Eduardo Peixoto-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcelo Volpon Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luiza da Silva Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luiza da Silva Lopes.

Ethics declarations

This study was designed according to the ethical guidelines published by the Brazilian College of Animal Experimentation (COBEA), protocol number 114/2012, and was approved by the Ethics Committee of Animal Experimentation of Ribeirao Preto Medical School, University of Sao Paulo (CETEA/FMRP-USP).

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the reported research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garcia, C.A.B., Catalão, C.H.R., Machado, H.R. et al. Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus. Childs Nerv Syst 33, 419–428 (2017). https://doi.org/10.1007/s00381-016-3313-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00381-016-3313-x

Keywords

Search

Navigation