Sıçanlarda Deneysel Beyin İskemisinde 2 Haftalık Naringin Uygulamasının Nörogenezis ve BDNF Düzeylerine Etkisi
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2023
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Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
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info:eu-repo/semantics/openAccess
Abstract
İskemik inme, dünya çapında önde gelen ölüm ve engelillik nedenidir ve hayatta kalanların
yarısından fazlası ciddi nörolojik sorunlarla yaşamlarına devam etmek zorunda kalır. Bu nedenle son
zamanlarda tıbbi çalışma alanında iskemik inme çok dikkat çekmiştir. Bu çalışmanın amacı deneysel
beyin iskemi-reperfüzyonunda naringin tedavisinin beyinde nörogenezis ve beyinden türetilen
nörotrofik faktör (BDNF) düzeylerine olan etkisini belirlemekti. Araştırma Selçuk Üniversitesi Deney
Hayvanları Araştırma ve Uygulama merkezinden temin edilen 8 haftalık 40 adet erkek Wistar tipi sıçan
üzerinde gerçekleştirildi. Deney grupları şu şekilde oluşturuldu; 1) Kontrol grubu, 2) Sham grubu, 3)
Beyin iskemi-reperfüzyonu grubu, 4) Beyin iskemi-reperfüzyon + çözücü grubu (14 gün uygulama), 5)
Beyin iskemi-reperfüzyon + Naringin (50 mg/kg/gün) (14 gün uygulama) grubu.
İskemi reperfüzyon gruplarında 30 dakika süreyle sağ ve sol karotid arter ligasyonu ile beyinde
global iskemi gerçekleştirildi. Naringin reperfüzyonu takiben, 14 gün boyunca intraperitoneal yolla
deney hayvanlarına uygulandı. İskemi-reperfüzyon uygulamasından 4 gün önce yeni nesne tanıma testi
ve rotarod testinin alıştırma fazına başlandı ve ameliyatten bir gün önce ve ameliyat sonrası 1., 7. ve 14,
günlerde rotarod ve yeni nesne tanıma testlerinin, test fazı ve nörolojik skorlama yapıldı. Deneylerin
bitiminde genel anestezi altındaki hayvanlar sakrifiye edildi ve beyinden hipokampus ve frontal korteks
dokuları alındı. Hipokampus ve frontal korteks dokularında çift kortin belirteci (DCX), nöronal çekirdek
belirteci (NeuN) ve BDNF, Real-Time qPCR analizi ve immunohistokimya yöntemleri ile
değerlendirildi.
İskemi-reperfüzyon nörolojik skor değerlerini yükseltirken, hipokampus ve frontal korteks
dokularında iskemi sonrası DCX, NeuN ve BDNF seviyeleri önemli şekilde düşüş gösterdi. Ancak
naringin takviyesi meydana gelen bozulmaları belirli oranda düzeltti (P<0.001).
Çalışmanın sonuçları 2 haftalık naringin tedavisinin sıçanlarda beyin iskemi ve reperfüzyonu
sonrası oluşan nörogenezis ve BDNF düzeylerinde bozulmalar üzerinde düzeltici etkilere sahip
olabileceğini göstermektedir.
Ischemic stroke is the leading cause of mortalitiy and disability worldwide with more than the half of survivors live with serious neurological sequelae thus; it has recently attracted a lot of attention in the field of medical study. The aim of this study was to determine the effect of naringin treatment on neurogenesis and brain-derived neurotrophic factor (BDNF) levels in the brain in experimental brain ischemia-reperfusion. The research was carried out on 40 8-weeks-old male Wistar type rats obtained from the Experimental Animals Research and Application Center of Selçuk University. Experimental groups were as follows; 1) Control group, 2) Sham group, 3) Brain ischemia-reperfusion group, 4) Brain ischemia-reperfusion + vehicle group (administered for 14 days), 5) Brain ischemia-reperfusion + Naringin group (100 mg/kg/day administered for 14 days). In the ischemia-reperfusion groups, global ischemia was performed in the brain by ligation of the right and left carotid arteries for 30 minutes. Naringin was administered to experimental animals by intragastric route for 14 days following reperfusion. The trainig phase of the new object recognition and rotarod tests, was started 4 days before ischemia-repefusion, and the test phase of each test together with neurological scoring were performed the day before and 1, 7 and 14 days after the operation. At the end of the experiment, animals have been sacrified and then hippocampus and frontal cortex tissues were taken from the brain. Double cortin marker (DCX), neuronal nuclear antigen marker (NeuN) and BDNF were evaluated in hippocampus and frontal cortex tissues by Real-Time qPCR analysis and immunohistochemistry methods. While ischemia-reperfusion increased the neurological score values, DCX, NeuN and BDNF levels decreased significantly after ischemia in hippocampus and frontal cortex tissues. However, naringin supplementation restored the deterioration to a certain extent. The results of the study show that 2-weeks naringin treatment may have protective effects on impaired neurogenesis and BDNF levels after brain ischemia and reperfusion in rats.
Ischemic stroke is the leading cause of mortalitiy and disability worldwide with more than the half of survivors live with serious neurological sequelae thus; it has recently attracted a lot of attention in the field of medical study. The aim of this study was to determine the effect of naringin treatment on neurogenesis and brain-derived neurotrophic factor (BDNF) levels in the brain in experimental brain ischemia-reperfusion. The research was carried out on 40 8-weeks-old male Wistar type rats obtained from the Experimental Animals Research and Application Center of Selçuk University. Experimental groups were as follows; 1) Control group, 2) Sham group, 3) Brain ischemia-reperfusion group, 4) Brain ischemia-reperfusion + vehicle group (administered for 14 days), 5) Brain ischemia-reperfusion + Naringin group (100 mg/kg/day administered for 14 days). In the ischemia-reperfusion groups, global ischemia was performed in the brain by ligation of the right and left carotid arteries for 30 minutes. Naringin was administered to experimental animals by intragastric route for 14 days following reperfusion. The trainig phase of the new object recognition and rotarod tests, was started 4 days before ischemia-repefusion, and the test phase of each test together with neurological scoring were performed the day before and 1, 7 and 14 days after the operation. At the end of the experiment, animals have been sacrified and then hippocampus and frontal cortex tissues were taken from the brain. Double cortin marker (DCX), neuronal nuclear antigen marker (NeuN) and BDNF were evaluated in hippocampus and frontal cortex tissues by Real-Time qPCR analysis and immunohistochemistry methods. While ischemia-reperfusion increased the neurological score values, DCX, NeuN and BDNF levels decreased significantly after ischemia in hippocampus and frontal cortex tissues. However, naringin supplementation restored the deterioration to a certain extent. The results of the study show that 2-weeks naringin treatment may have protective effects on impaired neurogenesis and BDNF levels after brain ischemia and reperfusion in rats.
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BDNF, DCX, Flavonoid, Naringin, NeuN, Nörogenezis, Neurogenesis
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Yılmaz, E., (2023). Sıçanlarda Deneysel Beyin İskemisinde 2 Haftalık Naringin Uygulamasının Nörogenezis ve BDNF Düzeylerine Etkisi. (Doktora Tezi). Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü, Konya.
