Progesteron Serebral İskemi Yapılan Erkek Ratlarda İskemik Hasarı Artırır

Year 2019, , 183 - 194, 31.08.2019

Mustafa Öğden , Bülent Bakar , Canan Altunkaya , Ahmet Turan Dağlı , Alemiddin Özdemir , Mehmet Faik Özveren

https://doi.org/10.24938/kutfd.531788

Abstract

Amaç: Günümüzde akut iskemik inme tedavisine yönelik literatürde
çok az sayıda kabul edilmiş etkili farmakolojik tedavi yöntemi bulunmaktadır. Bu
deneysel çalışma progesteronun erkek ratlarda oluşturulan geçici iskemi/ reperfüzyon
hasarı üzerine olan etkilerini araştırmak amacıyla yapıldı.

Gereç ve Yöntemler: Kontrol grubu (n=5) dışında, 20 adet Wistar albino erkek
sıçanı (Sham-A, Sham-C, PRG-A, PRG-C) dört gruba dağıtıldı ve geçici anevrizma klipleri
30 dakika boyunca internal karotid artere uygulandı. Klipler alındıktan dört saat
sonra, PRG-A ve PRG-C gruplarına intraperitoneal olarak progesteron uygulandı. Tüm
hayvanlar sakrifiye edildikten sonra, hipokampal cornu ammnonis CA 1, CA2, CA3 ve
parietal korteksteki piknotik ve nekrotik nöronal hücreler histopatolojik olarak
sayıldı. Ek olarak, doku interlökin (IL)-6, IL-10, kaspaz-3, HIF1 gen ekspresyon
seviyeleri ve real time polimeraz zincir reaksiyonu değerlendirildi.

Bulgular: Progesteronun iskeminin hem akut hemde kronik döneminde
iskemik nöronal doku hasarı üzerinde histopatolojik ve biyokimyasal veriler bakımından
iyileştirici etkilerinin olmadığı görüldü. Hatta progesteronun iskemi bulgularını
hem akut dönemde ve hem de kronik dönemde sağlıklı dokulara göre ve hatta sadece
cerrahi girişim yapılıp hiçbir deneysel ajan verilmeyen deney gruplarına göre belirgin
şekilde arttırdığı gözlendi.

Sonuç: Bu çalışma sonunda progesteronun erkek cinsiyetteki ratlarda
oluşturulan serebral iskemi/reperfüzyon hasarında tedavi edici etkinliğinin olmadığı
ve bu hasarı daha da artırdığı düşünüldü.

Keywords

Progesteron, inme, interlökin, HIF1, apopitozis

PROGESTERONE INCREASES THE ISCHEMIC DAMAGE IN MALE RATS WITH CEREBRAL ISCHEMIA REPERFUSION INJURY

Abstract

Objective: In
the current literature, there are few accepted pharmacological treatment
methods for acute ischemic stroke. This study was conducted to investigate the
effects of progesterone on transient ischemia / reperfusion injury in male
rats.

Material and Methods: A
total of 25 Wistar albino male and young rats were divided into 5 groups called
Control group, acute stage groups (Sham-A and PRG-A), and chronic stage groups (Sham-C
and PRG-C), randomly and their internal carotid arteries were compressed using
temporary aneurysm clips for 30 minutes. At 4 hours after removal of the clips,
progesterone was injected to the animals of the PRG-A and PRG-C group via intraperitoneal
route. After sacrifice of all animals, pyknotic and necrotic neuronal cells were
counted in hippocampal cornu amnonis (CA)1, CA2, CA3 and parietal cortical
regions, histopathologically. Tissue interleukin (IL)-6, IL-10, caspase-3, and hypoxia-inducible
factor-1 (HIF1) gene expression levels were evaluated using real time polymerase
chain reaction assay.

Results: Histopathological
and biochemical findings revealed that progesterone has no healing effects on
ischaemic neuronal tissue damage in either acute or chronic period. Moreover,
progesterone was found to significantly increase symptoms of ischaemia in both
acute and chronic periods compared to healthy control group and even compared
to Sham groups where I/R injury was applied and no experimental agent was
administered.

Conclusion: At
the end of this study, it was thought that progesterone had no therapeutic
effect on cerebral ischemia / reperfusion injury in male sex rats and it could
lead to increase it further, unfortunately.

Keywords

Progesterone, stroke, interleukin, HIF1, apoptosis

References

• 1. Elijovich L, Chong JY. Current and future use of intravenous thrombolysis for acute ischemic stroke. Curr Atherosclerol Rep. 2010;12(5):316-21.
• 2. Ishrat T, Sayeed I, Atif F, Stein DG. Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats. Brain Res. 2009;1257:94-101.
• 3. Espinosa-Garcia C, Aguilar-Hernandez A, Cervantes M, Moralí G. Effects of progesterone on neurite growth inhibitors in the hippocampus following global cerebral ischemia. Brain Res. 2014;1545:23-34.
• 4. Schumacher M, Robel P, Baulieu EE. Development and regeneration of the nervous system: a role for neurosteroids. Dev Neurosci. 1996;18(1-2):6-21.
• 5. Yousuf S, Atif F, Sayeed I, Tang H, Stein DG. Progesterone in transient ischemic stroke: a dose-response study. Psychopharmacology (Berl). 2014;231(17):3313-23.
• 6. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD. Gender-linked brain injury in experimental stroke. Stroke. 1998;29(1):159-66.
• 7. Murphy SJ, Traystman RJ, Hurn PD, Duckles SP. Progesterone exacerbates striatal stroke injury in progesterone-deficient female animals. Stroke. 2000;31(5):1173-8.
• 8. Coomber B, Gibson CL. Sustained levels of progesterone prior to the onset of cerebral ischemia are not beneficial to female mice. Brain Res. 2010;1361:124-32.
• 9. Wong R, Renton C, Gibson CL, Murphy SJ, Kendall DA, Bath PM. Progesterone treatment for experimental stroke: an individual animal meta-analysis. J Cereb Blood Flow Metab. 2013;33(9):1362-72.
• 10. Calvert JW, Cahill J, Yamaguchi-Okada M, Zhang JH. Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1alpha and its downstream target genes. J Appl Physiol. 2006;101(3):853-65.
• 11. Gredal H, Thomsen BB, Boza-Serrano A, Garosi L, Rusbridge C, Anthony D et al. Interleukin-6 is increased in plasma and cerebrospinal fluid of community-dwelling domestic dogs with acute ischaemic stroke. Neuroreport. 2017;28(3):134-140.
• 12. Li SJ, Liu W, Wang JL, Zhang Y, Zhao DJ, Wang TJ et al. The role of TNF-α, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy. Eur Rev Med Pharmacol Sci. 2014;18(6):905-9.
• 13. Waje-Andreassen U, Kråkenes J, Ulvestad E, Thomassen L, Myhr KM, Aarseth J et al. IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol Scand. 2005;111(6):360-5.
• 14. Habib P, Dang J, Slowik A, Victor M, Beyer C. Hypoxia-induced gene expression of aquaporin-4, cyclooxygenase-2 and hypoxia-inducible factor 1α in rat cortical astroglia is inhibited by 17β-estradiol and progesterone. Neuroendocrinology. 2014;99(3-4):156-67.
• 15. Mohamed RA, Agha AM, Nassar NN. SCH58261 the selective adenosine A (2A) receptor blocker modulates ischemia reperfusion injury following bilateral carotid occlusion: role of inflammatory mediators. Neurochem Res. 2012;37(3):538-47.