Absans epilepsili WAG/RİJ sıçanlarda N-(P-amilsinnamoil) antranilik asitin hipokampal endoplazmik retikulum stresi ve kan-beyin bariyeri bütünlüğü üzerine nöroprotektif etkisinin araştırılması
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2021
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İnönü Üniversitesi
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info:eu-repo/semantics/openAccess
Özet
Amaç: Absans epilepsi, genellikle kısa süreli bilinç kaybıyla karakterize nörolojik bir hastalıktır. Çalışmada amaç; ACA'nın absans epilepside koruyucu etkinliği olup olmadığını, ER stres ile KBB bütünlüğüne etkisini ortaya koymaktır. Ayrıca epilepsi tedavisinde kullanılan ancak ciddi yan etkileri olan hidrokortizonun, ACA'yla etkilerini karşılaştırarak, tedavide alternatif ajan olup olamayacağını saptamaktır. ER stres ve KBB bozulmasında patofizyolojik mekanizmayı açıklamak, epilepsi tedavisinde yeni yaklaşımların oluşumuna katkı sağlamaktır. Materyal ve Metot: Çalışmada 32 adet WAG/Rij dişi ve erkek sıçan kullanılarak, kontrol, DMSO+PBS, hidrokortizon ve ACA şeklinde 4 gruba ayrıldı (n=8). Kontrol grubundaki sıçanlara bir madde verilmedi. DMSO+PBS grubuna DMSO+PBS çözeltisi, ACA grubuna; 25 mg/kg/gün ACA, hidrokortizon grubuna 2.25 mg/kg/gün hidrokortizon (i.p.) günde bir kez, tek doz verildi. Sıçanların nöbetleri izlenerek, ağırlıkları ile yemler tartıldı. Perfüzyon-fiksasyondan sonra, dekapite edilen sıçanların hipokampüs ve somatosensoriyel kortekslerindeki ATF4, ATF6, CHOP ve GRP78 seviyeleri Western Blot ile ölçüldü. ZO-1, GFAP ve okludin seviyeleri immünohistokimyasal olarak incelendi. Bulgular: ACA, absans epilepsi nöbet sayısını ve ER stres indikatörlerini azaltmada daha etkili olurken, hidrokortizonun KBB hasarı üzerine daha koruyucu bir etkisinin olduğu tespit edilmiştir. Sonuç: ACA'nın absans epilepsi nöbet sayısını ve ER stresi azaltmada daha etkili olduğu, KBB bozulması üzerine hidrokortizon gibi koruyucu rolü olduğu bulundu. Anahtar Kelimeler: Absans epilepsi, ACA, ATF4, ATF6, CHOP, ER stres, GFAP, GRP78, hidrokortizon, KBB, okludin, WAG/Rij sıçan, ZO-1.
Aim: Absence epilepsy is a neurological disease characterized by short-term loss of consciousness. Purpose of the study; to reveal whether ACA has a protective effect in absence epilepsy, ER stress, BBB impairment. To determine whether hydrocortisone, which is used in the treatment of epilepsy but has serious side effects, can be an alternative agent in the treatment by comparing effects with ACA. To explain the pathophysiological mechanism in ER stress and BBB, contribute to the formation of new approaches in epilepsy treatment. Material and method: In the study, 32 WAG/Rij female, male rats were divided into 4 groups; control, DMSO+PBS, hydrocortisone, ACA (n=8). No substance was given to rats in control group. DMSO + PBS solution to DMSO + PBS group, ACA group; ACA of 25 mg/kg/day, hydrocortisone (i.p.), 2.25 mg/kg/day were administered once a day as a single dose to hydrocortisone group. Seizures of the rats were monitored, feeds and their weight were weighed. After perfusion-fixation, ATF4, ATF6, CHOP, GRP78 levels in the hippocampus and somatosensory cortex of decapitated rats were measured byWestern Blot. ZO-1, GFAP, occludin levels were examined by immunohistochemistry. Results: ACA was more effective in reducing the number of absence epilepsy seizures and ER stress indicators, while hydrocortisone was found to have a more protective effect on BBB damage. Conclusion: It was found that ACA was more effective in reducing number of absence epilepsy seizures and ER stress, and had a protective role like hydrocortisone on BBB impairment. Key Words: Absence epilepsy, ACA, ATF4, ATF6, BBB, CHOP, ER stress, GFAP, GRP78, hydrocortisone, occludin, WAG/Rij rat, ZO-1.
Aim: Absence epilepsy is a neurological disease characterized by short-term loss of consciousness. Purpose of the study; to reveal whether ACA has a protective effect in absence epilepsy, ER stress, BBB impairment. To determine whether hydrocortisone, which is used in the treatment of epilepsy but has serious side effects, can be an alternative agent in the treatment by comparing effects with ACA. To explain the pathophysiological mechanism in ER stress and BBB, contribute to the formation of new approaches in epilepsy treatment. Material and method: In the study, 32 WAG/Rij female, male rats were divided into 4 groups; control, DMSO+PBS, hydrocortisone, ACA (n=8). No substance was given to rats in control group. DMSO + PBS solution to DMSO + PBS group, ACA group; ACA of 25 mg/kg/day, hydrocortisone (i.p.), 2.25 mg/kg/day were administered once a day as a single dose to hydrocortisone group. Seizures of the rats were monitored, feeds and their weight were weighed. After perfusion-fixation, ATF4, ATF6, CHOP, GRP78 levels in the hippocampus and somatosensory cortex of decapitated rats were measured byWestern Blot. ZO-1, GFAP, occludin levels were examined by immunohistochemistry. Results: ACA was more effective in reducing the number of absence epilepsy seizures and ER stress indicators, while hydrocortisone was found to have a more protective effect on BBB damage. Conclusion: It was found that ACA was more effective in reducing number of absence epilepsy seizures and ER stress, and had a protective role like hydrocortisone on BBB impairment. Key Words: Absence epilepsy, ACA, ATF4, ATF6, BBB, CHOP, ER stress, GFAP, GRP78, hydrocortisone, occludin, WAG/Rij rat, ZO-1.
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Kaya, G,B, (2021), Absans epilepsili WAG/RİJ sıçanlarda N-(P-amilsinnamoil) antranilik asitin hipokampal endoplazmik retikulum stresi ve kan-beyin bariyeri bütünlüğü üzerine nöroprotektif etkisinin araştırılması İnönü Üniversitesi, Yayınlanmış, Doktora Tezi ,Malatya
