title: The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study.
abstract: OBJECTIVE
  In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock.
  
  
  METHODS
  Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40-50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups.
  
  
  RESULTS
  The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05).
  
  
  CONCLUSIONS
  The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey. drolcayeser@hotmail.com.|PK:29 03000, Afyonkarahisar, Turkey. drolcayeser@hotmail.com.
authors.forename: Olcay
authors.initials: O
authors.lastname: Eser
authors.affiliation: Department of Neurosurgery, Faculty of Meram Medicine, Selcuk University, Konya, Turkey.
authors.forename: Erdal
authors.initials: E
authors.lastname: Kalkan
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Cosar
authors.affiliation: Department of Neurology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yaman
authors.affiliation: Department Biochemistry, Faculty of Meram Medicine, Selcuk University, Konya, Turkey.
authors.forename: Sadik
authors.initials: S
authors.lastname: Büyükbaş
authors.affiliation: Department of Pathology, Faculty of Meram Medicine, Selcuk University, Konya, Turkey.
authors.forename: Mustafa Cihat
authors.initials: MC
authors.lastname: Avunduk
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, Afyon Kocatepe University, Afyonkarahisar, Turkey.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Fidan
keywords: Brain injury; FK 506; Hemorrhagic shock; Ischemia-reperfusion; Tacrolimus