Hindawi Publishing Corporation Stroke Research and Treatment Volume 2012, Article ID 809417, 8 pages doi:10.1155/2012/809417 Research Article Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat Zahra-Nadia Sharifi, 1 Farid Abolhassani, 2 Mohammad Reza Zarrindast, 3 Shabnam Movassaghi, 4 Nasrin Rahimian, 5 and Gholamreza Hassanzadeh 2 1 Institute for Cognitive Science Studies, Pezeshkpour Alley, Vali-e-Asr Street, 15948-34111 Tehran, Iran 2 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Enghelab Street, 14176-13151 Tehran, Iran 3 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Enghelab Street, 14176-13151 Tehran, Iran 4 Department of Anatomy, School of Medicine, Tehran Medical Branch, Islamic Azad University, Shariati Street, Zargandeh Street, 19168 Tehran, Iran 5 Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Dr. Gharib Street, 14197-31357 Tehran, Iran Correspondence should be addressed to Gholamreza Hassanzadeh, hassanzadeh@tums.ac.ir Received 22 May 2011; Revised 11 July 2011; Accepted 14 July 2011 Academic Editor: Arijana Lovrencic-Huzjan Copyright © 2012 Zahra-Nadia Sharifi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6mg/kg) was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP) 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage. 1. Introduction Reperfusion injury plays an important role in the brain ischemia cascade, which is involved in stroke and brain trauma. It is due to the inflammatory response of injured tissues [1]. Returned blood flow can reintroduce oxygen which can damage proteins, DNA, and plasma membranes of the cells. Plasma membrane damage may in turn induce the release of more free radicals. These processes may play an important role in redox signaling indirectly and cause cell apoptosis [2]. Certain areas of the brain and certain types of neurons which are more sensitive to cerebral ischemia are pyramidal neurons of the CA1 region of the hippocampus [3, 4]. Apoptosis is the most important process in CA1 neurons exposed to transient global ischemia. Apoptotic cell death of neurons can be limited by inhibition of macromolecular synthesis and of caspase activity [5]. Therefore, the attempts have predominantly been concentrated on prevention of acute cell death to help stroke patients. More than one hundred agents have proven to be neuroprotective in experi- mental models [6]. Unlike the promising results from animal models in preventing these types of cell death, unfortunately, no ef- fective pharmacologic strategy has been found to deal with the problem of ischemia. This may be due to lack of efficacy and presence of unwanted side effects [7, 8]. Recently, using immunophilin ligands has been consid- ered as a potential and appropriate strategy for neuroprotec- tion. Since it was observed that tacrolimus (FK506), a useful immunosuppressant used in organ transplantation, provides