Ulus Travma Acil Cerrahi Derg. 2015; 21(1): 1-8 | DOI: 10.5505/tjtes.2015.57894

Therapeutic evaluation of interleukin 1-beta antagonist Anakinra against traumatic brain injury in rats

Askin Esen Hasturk¹, Erdal Resit Yilmaz², Erhan Turkoglu², Hayri Kertmen², Bahriye Horasanli³, Nazli Hayirli⁴, Imge Berrin Erguder⁵, Oya Evirgen^4
1Department Of Neurosurgery, Oncology Training And Research Hospital, Ankara, Turkey
²Department Of Neurosurgery, Diskapi Yildirim Beyazit Training And Research Hospital, Ankara, Turkey
³Department Of Neurology, Baskent University Faculty Of Medicine, Ankara, Turkey
⁴Department Histology And Embryology, Ankara University Faculty Of Medicine, Ankara, Turkey
⁵Department Of Biochemistry, Ankara University Faculty Of Medicine, Ankara, Turkey

BACKGROUND: The aim of this study was to evaluate the therapeutic efficiency of Anakinra, an IL-1β antagonist with anti-inflammatory effects, in an experimental model of traumatic brain injury (TBI).
METHODS: Fifty-four rats underwent TBI after a weighted object was dropped onto a metal disc secured to their skulls. Animals were randomized into 3 main groups: control (n=18), TBI + saline (n=18; six animals per time-point) with samples obtained at the first, sixth and twenty-fourth h postoperatively, and TBI + Anakinra (n=18; six animals per time-point) with brain samples obtained at the first, sixth and twenty-fourth h postoperatively. Brain tissue and blood serum were extracted for the analysis of IL-1β, malondialdehyde, glutathione peroxidase, superoxide dismutase, and catalase levels. Tissue sections were evaluated histopathologically under a light microscope.
RESULTS: After trauma, tissue and serum IL-1β levels were significantly elevated and after Anakinra administration, these levels substantially decreased. Glutathione peroxidase, superoxide dismutase, and catalase activity decreased following TBI and Anakinra administration proved effective in increasing the activity of these antioxidant enzymes. Histopathological analysis confirmed that Anakinra might protect the brain tissue and nerve cells from injury.
CONCLUSION: Results demonstrate that Anakinra reduces the development of inflammation and tissue injury events associated with TBI.

Keywords: Antioxidant, anakinra, interleukin-1; neuroprotection; traumatic brain injury.

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Ýnterlökin 1-beta inhibitörü Anakinra’nýn sýçanlarda travmatik beyin hasarýna karþý terapötik etkinliðinin deðerlendirmesi

Askin Esen Hasturk¹, Erdal Resit Yilmaz², Erhan Turkoglu², Hayri Kertmen², Bahriye Horasanli³, Nazli Hayirli⁴, Imge Berrin Erguder⁵, Oya Evirgen^4
1Onkoloji Eðitim Ve Araþtýrma Hastanesi, Beyin Ve Sinir Cerrahisi Bölümü, Ankara, Türkiye
²Dýþkapý Yýldýrým Beyazýt Eðitim Ve Araþtýrma Hastanesi, Beyin Ve Sinir Cerrahisi Bölümü, Ankara, Türkiye
³Baþkent Üniversitesi Týp Fakültesi, Nöroloji Departmaný, Ankara, Türkiye
⁴Ankara Üniversitesi Týp Fakültesi, Histoloji Ve Embriyoloji Departmaný, Ankara, Türkiye
⁵Ankara Üniversitesi Týp Fakültesi, Biyokimya Departmaný, Ankara, Türkiye

AMAÇ: Bu çalýþmanýn amacý, deneysel travmatik beyin hasarý (TBH) modelinde interlökin 1 beta (IL-1β) inhibitörü Anakinra’nýn tedavi edici etkinliðinin deðerlendirilmesidir.
GEREÇ VE YÖNTEM: Elli dört Wistar albino sýçana anestezi uygulamasý sonrasý kafatasý üzerine konan bir metal disk üzerine 2 metreden 450 g aðýrlýk düþürülerek deneysel kapalý kafa travmasý oluþturuldu. Hayvanlar üç ana gruba ayrýldý: Kontrol (n=18), TBH + salin (n=18; zaman baþýna altý hayvan) numuneler bir, altý ve 24 saat sonra alýndý ve TBH + Anakinra (n=18; zaman baþýna altý hayvan) numuneler bir, altý ve 24 saat sonra alýndý. IL-
1β, malondialdehit, glutatyon peroksidaz, süperoksit dismutaz ve katalaz düzeylerinin analizi için beyin dokusu ve kan örnekleri alýndý. Doku kesitleri histopatolojik olarak ýþýk mikroskobunda deðerlendirildi.
BULGULAR: Travma sonrasý, doku ve serum IL-1β düzeyleri önemli ölçüde artmýþtý ve bu düzeyler Anakinra verilmesinden sonra azaldý. TBH takiben glutatyon peroksidaz, süperoksit dismutaz ve katalaz aktivitesi azalmýþ ve Anakinra uygulanmasý bu antioksidan enzimlerin aktivitesini artýrmada etkili olmuþtur. Histopatolojik analiz Anakinra’nýn beyin dokusu ve sinir hücrelerini travmadan koruyabileðini doðrulamýþtýr.
TARTIÞMA: Anakinra’nýn TBH ile ortaya çýkan enflamasyon ve doku hasarý geliþimini azalttýðýný göstermektedir.

Anahtar Kelimeler: Anakinra, antioksidan, interlökin-1; nöroproteksiyon; travmatik beyin hasarý.

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