Ulus Travma Acil Cerrahi Derg. 2023; 29(2): 155-162 | DOI: 10.14744/tjtes.2023.33644

Deneysel kafa travma araþtýrmasýnda takrolimus’un histopatolojik etkinliði

Ali Atadað¹, Ýbrahim Erkutlu², Ahmet Sarper Bozkurt³, Ömer Eronat⁴, Yýldýz Büyükdereli Atadað⁵, Necati Üçler², Abidin Murat Geyik^2
1Abdulkadir Yüksel Devlet Hastanesi, Beyin ve Sinir Cerrahisi Kliniði, Gaziantep
²Gaziantep Üniversitesi Týp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalý, Gaziantep
³Gaziantep Üniversitesi Týp Fakültesi, Fizyoloji Anabilim Dalý, Gaziantep
⁴Gaziantep Üniversitesi Týp Fakültesi, Patoloji Anabilim Dalý, Gaziantep
⁵Abdulkadir Yüksel Devlet Hastanesi, Aile Hekimliði Kliniði, Gaziantep

AMAÇ: Deneysel kafa travmasý oluþturulan sýçanlarda, bir immunsupresif ajan olan takrolimus’un (FK506) oluþacak sekonder beyin hasarýna karþý koruyucu etkisini araþtýrmak amaçlandý.
GEREÇ VE YÖNTEM: Kýrk adet Sprague-Dawley tipi 250-350 gr aðýrlýðýnda 10–12 haftalýk sýçanlar cinsiyet seçimi yapýlmaksýzýn kullanýldý. Her grupta sekiz sýçan olacak þekilde beþ gruba (Sham kontrol, Negatif kontrol, Pozitif kontrol, Vehicle kontrol, Tedavi) ayrýlan denekler, uygun þartlarda kafa travmasý oluþturulduktan bir ay sonra sakrifiye edilerek beyinleri en blok olarak çýkarýldý ve histopatolojik olarak deðerlendirildi. Sekonder beyin hasarý, beyin dokusunda oluþacak gliosizin GFAP boyanmasý sonrasý Immun Reaktivite Skoru (IRS) ile deðerlendirildi.
BULGULAR: Tüm gruplarýn histopatolojik IRS deðerleri deðerlendirildiðinde tüm gruplar arasýnda anlamlý istatistiki farklarýn olduðu gözlendi. Daha sonra ikili gruplar þeklinde IRS deðerinin en fazla tedavi grubunda arttýðý (p<0.05) fakat Negatif Kontrol, Pozitif Kontrol ve Taþýyýcý Kontrol gruplarýnda artmasýna raðmen istatistiki anlam ifade etmediði gözlendi. Sham grubunda ileri derece bir histopatolojik reaksiyon skorunun en az oranda görüldüðü tespit edildi.
TARTIÞMA: FK506 verilen grupta travmatik alandaki gliozisin diðer kontrol gruplarýna göre istatistiki olarak belirgin olarak artýþ gösterdiði görüldü. Bu durum FK506’nýn henüz açýklanamayan bir mekanizma ile gliozisi engelleyemediði hatta arttýrdýðýný göstermektedir. Sonuç olarak, FK506 immunosupresif ajanýnýn beklenin aksine beyindeki travma sonrasý hasarý azaltmadýðý, aksine gliozisi arttýrdýðý ortadadýr.

Anahtar Kelimeler: FK506, gliozis; kafa travmasý; sekonder beyin hasarý; takrolimus.

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Histopathological efficacy of tacrolimus in an experimental head trauma study

Ali Atadað¹, Ýbrahim Erkutlu², Ahmet Sarper Bozkurt³, Ömer Eronat⁴, Yýldýz Büyükdereli Atadað⁵, Necati Üçler², Abidin Murat Geyik^2
1Department of Neurosurgery, Abdulkadir Yüksel State Hospital, Gaziantep-Türkiye
²Department of Neurosurgery, Gaziantep University Faculty of Medicine, Gaziantep-Türkiye
³Department of Physiology, Gaziantep University Faculty of Medicine, Gaziantep-Türkiye
⁴Department of Pathology, Gaziantep University Faculty of Medicine, Gaziantep-Türkiye
⁵Department of Family Medicine, Abdulkadir Yüksel State Hospital, Gaziantep-Türkiye

BACKGROUND: This study aimed to investigate the protective effect of tacrolimus (FK506), an immunosuppressive agent, on secondary brain damage in rats with experimental head trauma.
METHODS: 40 Sprague-Dawley rats, aged 10–12 weeks and weighing 250–350 g, were used without gender selection. The subjects that were divided into five groups of 8 rats per group (sham control, negative control, positive control, vehicle control, and treatment) were sacrificed 1 month after head trauma was induced under appropriate conditions, their brains were then removed en bloc and evaluated histopathologically. Secondary brain injury was evaluated with the immunoreactive score (IRS) after Glial Fibrillary Acid Protein staining of gliosis that would occur in brain tissue.
RESULTS: The evaluation of the histopathological IRS values of all groups showed significant statistical differences between all groups. The pairwise group comparison revealed the highest increase in IRS value in the treatment group (p<0.05), with no statistical significance despite the increase in the negative control, positive control, and vehicle control groups. The sham group had the lowest rate of severe histopathological reaction score.
CONCLUSION: It was observed that the group treated with FK506 had a statistically significant increase in gliosis in the traumatic area compared to the other control groups. This shows that FK506 cannot prevent and even increase gliosis by a mechanism that has not yet been clarified. In conclusion, it is obvious that the FK506 immunosuppressive agent does not reduce post-traumatic brain injury; on the contrary, it increases gliosis.

Keywords: K506, gliosis; head trauma; secondary brain injury; tacrolimus.

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