Browsing by Author "Alkan, Tülin"
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Item An anatomical and pathological evaluation of middle cerebral artery occlusion in rats(Taylor & Francis, 2000) Kahveci, Nevzat; Alkan, Tülin; Korfalı, Ender; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahisi Anabilim Dalı.; 0000-0003-0841-8201; AAG-7070-2021; AAH-1792-2021Adult male Sprague-Dawley rats (n = 87) weighing 350-400g were used for studying the anatomy of the horizontal segment of middle cerebral artery and infarct area after occlusion of the artery. In the experimental group (n = 27) middle cerebral artery was coagulated 3-4 mm length from the origin of the lateral striate arteries to the inferior cerebral vein and divided. Control rats (n = 20) had all the surgical procedures except occlusion. Another group of rats (n = 40) were used to determine the anatomical variations of middle cerebral artery after intracarotid carbon black injection. Five major patterns of middle cerebral artery were observed and two of them were major and constituted 92.5% of rats. Twenty-four hours after middle cerebral artery occlusion, all animals were neurologically evaluated. On the third day after occlusion the brains were stained with 2% 2,3,5-triphenyltetrozolium chloride. The area of infarction was assessed by computerized analysis method. In our study after determining the Variations of the middle cerebral artery and its branches in our strain of rats, we were able to achieve 92.5% grade III and IV infarcted area.Publication Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury(TÜBİTAK, 2020-05-31) Al, Nevin; Çakir, Aysen; Koç, Cansu; Cansev, Mehmet; Alkan, Tülin; ÇAKIR, AYŞEN; KOÇ, CANSU; CANSEV, MEHMET; ALKAN, TÜLİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; 0000-0001-6466-5042; AAA-4754-2022; A-6819-2018; M-9071-2019; AAH-1792-2021Background/aim: Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting.Materials and methods: Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) - an oxidative stress-sensitive protein.Results: Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia.Conclusion: These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.Item Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury(Springer Wien, 2010-06) Türkkan, Alper; Alkan, Tülin; Gören, Bülent; Kocaeli, Hasan; Akar, Eylem; Korfali, Ender; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; AAH-1792-2021; AAH-1718-2021; 25029159600; 6601953747; 6602543716; 6603500567; 26634688200; 7004641343Ischemic spinal cord injury is a chain of events caused by the reduction and/or cessation of spinal cord blood flow, which results in neuronal degeneration and loss. Ischemic postconditioning is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion and has been shown to reduce the infarct size in cerebral ischemia. Our study aimed to characterize the relationship between the neuronal injury-decreasing effects of citicoline and ischemic postconditioning, which were proven to be effective against the apoptotic process. Spinal cord ischemia was produced in rats using an intrathoracic approach to implement the synchronous arcus aorta and subclavian artery clipping method. In our study, 42 male Sprague-Dawley rats (309 +/- 27 g) were used. Animals were divided into sham operated, spinal ischemia, citicoline, postconditioning, and postconditioning citicoline groups. Postconditioning was generated by six cycles of 1 min occlusion/5 min reperfusion. A 600 mmol/kg dose of citicoline was given intraperitoneally before ischemia in the citicoline and postconditioning citicoline groups. All rats were sacrificed 96 h after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9, and bax immune staining were performed. Caspase 3, caspase 9, bax, and bcl-2 were used as apoptotic and antiapoptotic markers, respectively. The blood pressure values obtained at the onset of reperfusion were significantly lower than the preischemic values. A difference in immunohistochemical scoring was detected between the caspase 3, caspase 9, bax, and bcl-2 groups. When comparisons between the ischemia (groups 2, 3, 4, and 5) and sham groups (group 1) were performed, a significant increase in caspase 3, caspase 9, bax, and bcl-2 was detected. When comparing the subgroups, the average score of caspase 9 was found to be significantly higher in ischemia group 2. The average score of bcl-2 was also found to be significantly higher in postconditioning and citicoline group 5. It is thus thought that combining citicoline with postconditioning provides protection by inhibiting the caspase pathway and by increasing the antiapoptotic proteins.Item Deneysel olarak travmatik beyin hasarı oluşturulan ratlarda serum pNF-H düzeyinin beyin hasarını göstermede etkinliği(Bursa Uludağ Üniversitesi, 2021-06-15) Çıkrıklar, Halil İbrahim; Durak, Vahide Aslıhan; Alkan, Tülin; Aydin, Birnur; Sığırlı, Deniz; Salcı, Hakan; Armağan, Erol; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Acil Tıp Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Cerrahi Anabilim Dalı.; 0000-0002-8073-6207; 0000-0003-0836-7862; 0000-0001-6466-5042; 0000-0002-8193-474X; 0000-0002-4006-3263; 0000-0001-6548-8754Çalışmamızın amacı deneysel olarak hafif travmatik beyin hasarı oluşturulan sıçanlardan alınan serum örneklerinde pNF-H düzeyinin hasarı göstermede etkin olup olmadığını araştırmaktır. Marmarou modelinin modifiye edilerek kullanıldığı deneysel çalışmamızda farklı yüksekliklerden farklı ağırlıklarda bilyeler serbest düşme yöntemiyle bırakılarak sırayla 0.05, 0.1, 0.2 ve 0.4 Newton şiddetinde travma oluşturulması hedeflendi. Travmanın indüksiyonundan 2 saat sonra sıçanların kalbinden alınan kanlarda pNF-H düzeyi araştırıldı. Sonuç olarak deneysel olarak hafif travmatik beyin hasarı oluşturduğumuz ratlarda 2.saatte alınan kanlarda pNF-H düzeylerindeki değişiklikler istatistiksel olarak anlamlı bulunmamıştır. Bu sonuçlar hafif travmatik beyin hasarından sonraki 2.saatte kanda çalışılan pNF-H’ın tanısal olarak etkin olmadığını göstermektedir.Item Deneysel travmatik beyin hasarında üridin ve terapötik hipotermi kombinasyonunun olası koruyucu etkinliğinin araştırılması(Bursa Uludağ Üniversitesi, 2022-05-13) Durak, Vahide Aslıhan; Alkan, Tülin; Cansev, Mehmet; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0003-0836-7862Travmatik beyin hasarı dünya çapında morbidite ve mortalitesi yüksek bir acil durumdur. Hastaneye başvuran hastaların çoğuna hafif travmatik beyin hasarı tanısı konmakla birlikte hastalarda uzun dönemde kalıcı hasarlar bırakabilmektedir. Travmatik beyin hasarı fizyopatolojik süreçlerinde birbirini takip eden; primer hasar ve sekonder hasar dönemi yer almaktadır. Primer beyin hasarı travmadan hemen sonra oluşmakta iken sekonder hasar primer hasardan sonra saatler ve günler sonra ortaya çıkmkatadır. Çalışmamızın amacı; deneysel olarak travmatik beyin hasarı modeli uygulaması ile sekonder hasar dönemi ile ilişkili oksidatif, inflamatuar ve apoptotik parametrelerde meydana gelen değişiklikleri incelemek ve Üridin ve/veya hipotermi kombine tedavisinin nöroprotektif etkisini araştırmaktır. Çalışmamızda, Marmarou ve arkadaşlarının tanımladığı serbest ağırlık düşürme modeli kullanılarak travmatik beyin hasarı oluşturulmuş ve hafif hipotermi (32-34.0±1°C) 4 saat boyunca uygulanmıştır. Üridin travmatik beyin hasarını takiben 7 gün boyunca 500mg/kg intraperitoneal uygulanmıştır. Takiben beyin dokusu analizleri, TTC, Western Blot ve ELISA kitleri kullanılarak yapılmıştır. Oksidatif parametreler içerisinden Glutatyon Peroksidaz kombine tedavi uygulaması ile artarken, Katalaz ve Myeloperoksidaz azalmıştır. İnflamatuar belirteçlerden olan İnterlökin-1β ve İnterlökin-6 ise kombine tedavi uygulaması ile azalma göstermiştir. Nekrotik süreçte görev alan Poli ADP-riboz polimeraz-1 ise TBH sonrası artarken, hipotermi, üridin ve kombine tedavi uygulaması ile azalmıştır. Travmatik beyin hasarına yaklaşımda esas hedef sekonder hasar döneminde oluşan etkilere karşı hastayı korumak olup çalışmamızda Üridin-hipotermi kombinasyon tedavisinin etkinliği yedi günlük tedavi uygulaması sonrasında gösterilmiş olup bu açıdan literatürde ilk olma özelliği taşımaktadır. Bu alanda yapılacak diğer çalışmalar ile hafif travmatik beyin hasarında rutin uygulamada kullanılabilecek bir tedavi yaklaşımı olması ve travma hastasının yönetimi kılavuzlarında yer alması hedeflenmektedir. Travmatik beyin hasarı dünya çapında morbidite ve mortalitesi yüksek bir acil durumdur. Hastaneye başvuran hastaların çoğuna hafif travmatik beyin hasarı tanısı konmakla birlikte hastalarda uzun dönemde kalıcı hasarlar bırakabilmektedir. Travmatik beyin hasarı fizyopatolojik süreçlerinde birbirini takip eden; primer hasar ve sekonder hasar dönemi yer almaktadır. Primer beyin hasarı travmadan hemen sonra oluşmakta iken sekonder hasar primer hasardan sonra saatler ve günler sonra ortaya çıkmkatadır. Çalışmamızın amacı; deneysel olarak travmatik beyin hasarı modeli uygulaması ile sekonder hasar dönemi ile ilişkili oksidatif, inflamatuar ve apoptotik parametrelerde meydana gelen değişiklikleri incelemek ve Üridin ve/veya hipotermi kombine tedavisinin nöroprotektif etkisini araştırmaktır. Çalışmamızda, Marmarou ve arkadaşlarının tanımladığı serbest ağırlık düşürme modeli kullanılarak travmatik beyin hasarı oluşturulmuş ve hafif hipotermi (32-34.0±1°C) 4 saat boyunca uygulanmıştır. Üridin travmatik beyin hasarını takiben 7 gün boyunca 500mg/kg intraperitoneal uygulanmıştır. Takiben beyin dokusu analizleri, TTC, Western Blot ve ELISA kitleri kullanılarak yapılmıştır. Oksidatif parametreler içerisinden Glutatyon Peroksidaz kombine tedavi uygulaması ile artarken, Katalaz ve Myeloperoksidaz azalmıştır. İnflamatuar belirteçlerden olan İnterlökin-1β ve İnterlökin-6 ise kombine tedavi uygulaması ile azalma göstermiştir. Nekrotik süreçte görev alan Poli ADP-riboz polimeraz-1 ise TBH sonrası artarken, hipotermi, üridin ve kombine tedavi uygulaması ile azalmıştır. Travmatik beyin hasarına yaklaşımda esas hedef sekonder hasar döneminde oluşan etkilere karşı hastayı korumak olup çalışmamızda Üridin-hipotermi kombinasyon tedavisinin etkinliği yedi günlük tedavi uygulaması sonrasında gösterilmiş olup bu açıdan literatürde ilk olma özelliği taşımaktadır. Bu alanda yapılacak diğer çalışmalar ile hafif travmatik beyin hasarında rutin uygulamada kullanılabilecek bir tedavi yaklaşımı olması ve travma hastasının yönetimi kılavuzlarında yer alması hedeflenmektedir.Item Dexamethasone prevents hypoxic-ischemic brain damage in the neonatal rat(Monduzzi Editore, 1997) Alkan, Tülin; Kahveci, Nevzat; Kahveci, Zeynep; Korfalı, Ender; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirurji Anabilim Dalı.; AAH-1792-2021; AAG-7070-2021In our study the effect of dexamethasone 3 hours before the hypoxic-ischemic brain damage were investigated in neonatal rats. 7 day old rats were undergone right CCA ligation followed by 2 hours hypoxic exposure. 7 day after the insult the brains were sectioned coronally +2, -2 mm from bregma and immersed in TTC. In vehicle treated group there was a marked infarction throughout cortex and striatum, disintegration of the structures of the right hemisphere and liquefication. In the Ist coronal slice 18.33% and in the IInd 32.76% of infarct area was detected. H&E and Nissl stainings also showed extensive neuronal degeneration. Dexamethasone group had no gross infarction and histopathological examination. showed only mild degree of ischemic changes.Item Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats(Elsevier, 2010-02) Türeyen, Kudret; Şahin, Soner; Alkan, Tülin; Temel, Şehime Gülsün; Tolunay, Şahsine; Korfali, Ender; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; AAH-2892-2021; AAH-1792-2021; AAG-8385-2021; 8272141000; 6601953747; 6507885442; 6602604390; 7004641343The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operate 1; Group 2, saline; Group 3, citicoline (400 mg/kg intraperitoneal.); Group 4, hypothermia (34 +/- 1 degrees C); Group 5, citicoline + hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical (mean standard deviation, 0.71 +/- 0.75) was lower compared to Groups 3, 4 and 5 (2.33 +/- 0.81; 3.00 +/- 0.00; 2.20 +/- 0.83; p < 0.05). There was higher expression of cispase-3 proteins in Group 2 (2.28 +/- 0.95) compared to Group 5 (1.50 +/- 0.83; p < 0.05). Bax proteins were also increased in Group 2 (1.85 +/- 1.06) compared to Group 5 (0.40 +/- 0.54) and in Group 4 (2.00 +/- 0.00) compared to Group 5 (0.40 +/- 0.54; p < 0.05). Significant differences in caspase-9 immunostaining scores were found in Group 2 (2.29 +/- 0.96) compared to Group 5 (0.20 +/- 0.44) (p < 0.05); Group 3 (1.00 +/- 0.70) compared to Group 5 (0.20 +/- 0.44: p, < 0.05); and Group 4 (3.00 +/- 0.00; p < 0.05) compared to Group 5 (0.40 +/- 0.54; p < 0.05). Thus by suppressing apoptotic processes citicoline with hypothermia is more effective than ;either used alone in ameliorating cerebral damage after transient focal ischemia.Item The effects of drugs on intracranial pressure, cerebral perfusion pressure and histopathological investigation of the infarct areas in focal cerebral ischemia model in rats(Monduzzi Editore, 1997) Kahveci, Nevzat; Alkan, Tülin; Kahveci, Ferda Şöhret; Korfalı, Ender; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Anesteziyoloji ve Reanimasyon Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirurji Anabilim Dalı.; AAH-1792-2021; AAG-7070-2021The effects of neuroprotective drugs in focal cerebral ischemia induced after MCA occlusion were investigated in adults rats. Group I rats (n:10) received nimodipine (1 mg/kg/min); Group II (n:10) etomidate (75 mg/kg, iv + 0.5 mg/kg/min iv maintenance); Group III (n:10) lidocaine (5 mg/kg iv + 0.4 mg/kg/min iv maintenance); Group IV (n:12) vehicle solution. In all groups rats were observed 300 min after MCAO and MABP, ICP measurements were recorded at 30 min intervals. There was no change in MABP values in Group I and II whilst these values decreased in Group III and IV. ICP increased in all groups. 24 h after occlusion in TTC stained brain sections smaller infarct areas were observed in Group I and II comparing to Group III and IV. Histopathological examination confirmed the findings. In conclusion, nimodipine has a protective effect on ICP, CPP and infarct area whereas etomidate has limited and lidocaine no effect at all.Item Effects of hypoxic preconditioning in antioxidant enzyme activities in hypoxic-ischemic brain damage in immature rats(Türk Nöroşurji Derneği, 2008-04) Alkan, Tülin; Gören, Bülent; Vatansever, Ebru; Sarandöl, Emre; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0001-6466-5042; 0000-0002-2593-7196; AAH-1792-2021; ABE-1716-2020; AAH-1718-2021; 6601953747; 6602543716; 16070622700; 55943324800Aim: HI (hypoxic-ischemic) brain injury is a major cause of neonatal mortality and longterm neurological morbidity. The aim of the present study was to investigate the effects of HPC (hypoxic preconditioning) on the oxidative-antioxidative status in the neonatal HI brain model. Material and Methods: Fifty five 7-day-old rats were placed into; Control, HPC, HPC+HI insult, and HI insult groups. HPC, The HPC+HI insult groups were subjected to hypoxia (37°C, 8%O2) and the control group to normoxia for 2.5 hrs. Twenty-four hours later, the rats in the HPC+HI insult and HI insult groups were exposed to cerebral HI produced by unilateral right common carotid artery (CCA) occlusion combined with 90 min hypoxia. Four hours after recovery, the malondialdehyde (MDA) level and the activities of superoxide dismutase (SOD), and glutathione peroxidase (GPx) were determined in the brain tissues of the rats. Results: The findings of the present study suggest increased lipid peroxidation and/or decreased antioxidant activity in the brain of the HI rats. Conclusion: The beneficial effects of HPC might not be related to the alterations in the antioxidative activity.Item Effects of intranigral vs intrastriatal fetal mesencephalic neural grafts on motor behavior disorders in a rat Parkinson model(Elsevier, 2005) Gören, Bülent; Kahveci, Nevzat; Eyigör, Özhan; Alkan, Tülin; Korfalı, Ender; Özlük, Kasım; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahisi Anabilim Dalı.; 0000-0003-3463-7483; 0000-0003-0841-8201; ABE-5128-2020; AAH-1718-2021; AAG-7070-2021; 6602543716; 6602597846; 6603109907; 6601953747; 7004641343; 6602676331Background: Numerous experimental and clinical studies have shown that intrastriatal fetal mesencephalic grafts grow, survive, and reinnervate host brain tissue, resulting in partial recovery of motor deficits. In addition, pharmacological evidence indicates that these grafts increase dopamine secretion in lesioned brain. However, to date, no grafting method has completely restored the nigrostriatal pathway, and there is no consensus on optimal graft numbers or locations. This study compared outcomes with multiple striatal grafts vs a single intranigral graft in a rat model of Parkinson disease. Methods: Forty-one female Wistar rats weighing 200 to 250 g were used. First, baseline rotational behavior testing with amphetamine injection was done to identify each animal's dominant nigrostriatal pathway (left vs right hemisphere). Some rats then received a unilateral intranigral injection of 6-hydroxydopamine (4 mu L [8 mu g]) to produce the Parkinson model lesion, and rotational testing was repeated. One group of the lesioned rats received a single intranigral injection of suspended fetal ventral mesencephalic cells (n = 11), and another received multiple intrastriatal grafts of the same type (n = 11). Results: Both grafted groups showed significant improvement on rotational testing with amphetamine and apomorphine at 6 weeks "postgrafting" (P <.001 for "postlesioning" vs postgrafting results in each of the 2 groups); however, the animals with multiple intrastriatal grafts showed complete recovery from motor asymmetry, whereas the rats with single intranigral grafts showed only partial improvement. Conclusion: The findings indicate that multiple intrastriatal grafts result in significantly greater functional improvement than single intranigral grafts in this rat Parkinson model.Item Experimental subarachnoid haemorrhage models in rats(Springer-Verlag Wien, 2002) Kanpolat, Y.; Alkan, Tülin; Korfalı, Ender; Kahveci, Nevzat; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0003-0841-8201; AAG-7070-2021; 6601953747; 7004641343; 6602597846There is no comprehensive and reliable model available in small animals that are suitable for the study of subarachnoid haemorrhage (SAH). In the study we reviewed the advantages and disadvantages of available SAH models in rats and presented our model. Experimental SAH was induced in a group of 350-450 g SpragueDawley rats. A 2 mm-diameter burr hole was drilled and, working under a microscope, haemorrhage was produced by transclival puncture of the basilar artery with a 20 mum thick piece of glass. The rats were assigned to either the experimental group (n: 7) or the control group (n: 7). Local cerebral blood flow (LCBF), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured for 60 min after SAH, after which the rats were decapitated. Microscopic examinations were done on three different segments of the basilar artery. There was a significant and sharp drop in LCBF just after SAH was induced (56.17 +/- 12.80 mILD/min/100 g and 13.57 +/- 5.85 mILD/min/100 g for baseline and post-SAH, respectively; p < 0.001), the flow slowly increased by the end of the experiment but never recovered to pre-SAH values (43,63 +/- 7.6 mILD/min/ 100 g, p < 0.05). ICP (baseline 7.33 +/- 0.8 mmHg) increased acutely to 70.6 +/- 9.2 mmHg, and also returned to normal levels by 60 min after SAH. CPP (baseline 75.1 +/- 4.9 mmHg) dropped accordingly (to 21.0 +/- 6.3 mmHg) and then increased, reaching 70.1 +/- 4.9 mmHg at 60 min after SAH. Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer. We present an inexpensive and reliable model of SAH in the rat that allows single and multiple haemorrhages and to study the early and late course of pathological changes.Item Hipoksik iskemik beyin hasarı oluşturulan yenidoğan sıçanlarda histon deasetilaz aktivitesinin nöroproteksiyona etkisi(Uludağ Üniversitesi, 2014-06-16) Koyuncuoğlu, Türkan; Alkan, Tülin; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Fizyoloji Anabilim Dalı.Neonatal hipoksik-iskemik beyin hasarı serebral palsi, epilepsi, öğrenme güçlüğü ve neonatal mortalite gibi nörolojik defisitlere sebep olur. Bu çalışmada, sağ kommon karotid arter oklüzyonu ile iskemi oluşturularak, hipoksiye maruz bırakılan sıçanlarda üridin tedavisi ile gözlemlenen nöroproteksiyonda histon asetilazların katılımı araştırıldı. Anestezi altında yedi günlük sıçanlara sağ kommon karotid arter koterizasyonunu takiben 150 dakika süre ile hipoksik karışım solutuldu. Deney hayvanları; Sham grubu (n:8); intraperitoneal (i.p.) olarak serum fizyolojik uygulanan Kontrol grubu (n:14) ve i.p. 500 mg/kg doz üridin uygulanan Üridin grubu (n:14) olmak üzere 3 gruba ayrıldılar. Serum fizyolojik ve üridinin ilk dozu iskemi-hipoksi uygulamasından hemen sonra, 2. ve 3. dozları ise yavru sıçanlar sırasıyla 8 ve 9 günlük iken uygulandılar. Bu çalışmada hipoksi-iskemi sürecinde 7 günlük yenidoğan sıçanlarda üridin uygulamasının histon deasetilaz aktivitesini azaltarak nöroprotektif etki gösterdiği gözlemlenmiştir.Item Hypothermia in neuronal protection(Lippincott Williams & Wilkins, 2001-06) Alkan, Tülin; Bekar, Ahmet; Korfalı, Ender; Uludağ Üniversitesi/Tıp Fakültesi/Psikiyatri Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroşurji Bölümü.; AAH-1792-2021; 6601953747; 6603677218; 7004641343During the past decade, it has been repeatedly shown that mild to moderate hypothermia (32-34 degreesC) reduces neurologic injury in animal models of focal or global ischemia, and of traumatic injury. This has led to renewed interest in the application of hypothermia for managing head injury, stroke, and cardiac arrest and for undertaking aneurysm surgery. This article reviews the relevant literature and presents the authors' experience with intracerebral hemorrhage treated under hypothermia.Item Long-term cognitive effects of uridine treatment in a neonatal rat model of hypoxic-ischemic encephalopathy(Elsevier, 2017-01-20) Gören, Bülent; Çakır, Aysen; Öçalan, Buşra; Koçoğlu, Sema Serter; Alkan, Tülin; Cansev, Mehmet; Kahveci, Nevzat; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0001-7729-7373; 0000-0002-3405-3640; 0000-0001-6466-5042; 0000-0003-0841-8201; 0000-0003-2918-5064; A-6819-2018; M-9071-2019; AAH-1718-2021; N-9927-2019; AAH-1792-2021; AAG-7070-2021; 0000-0001-6466-5042; 6602543716; 57191915856; 57191911801; 57193141905; 6601953747; 8872816100; 6602597846Hypoxic-ischemic encephalopathy (HIE), is the most common brain disorder in neonates during the perinatal period, which, to date, can only be managed to some extent by hypothermia. Uridine is the principal circulating pyrimidine in humans which is utilized as a precursor for membrane phospholipid biosynthesis. Uridine has recently been shown to provide clinical benefit in treatment of Alzheimer's disease due to its involvement in increasing number of brain synapses along with other phospholipid precursors. We previously showed that uridine treatment ameliorated brain damage by reducing apoptosis in a rat model of neonatal HIE. The aim of the present study was to investigate the effects of uridine administration on cognitive functions during periadolescent period in rats subjected to hypoxic-ischemic (HI) brain damage in neonatal period. Male newborn rats were subjected to HI insult on postnatal day 7 (P7) and were injected intraperitoneally with either saline or uridine (500 mg/kg) for three consecutive days. Part of pups in each group were sacrificed on P10 to collect brain samples for active Caspase-3 analyses and the remaining pups were raised through P40 to evaluate early reflexes, sensorimotor coordination and learning and memory functions by Negative Geotaxis (NG), Beam Walking (BW) and Morris Water Maze (MWM) tasks, respectively. Confirming our previous findings, we showed that uridine administration reduced apoptotic cell damage on P10. No significant difference was observed between uridine and saline groups in early reflexes or sensorimotor coordination. On the other hand, rats receiving uridine displayed improved learning and memory in MWM during periadolescent period. We conclude that uridine treatment improves learning and memory in the long term by, probably, reducing apoptotic cell death in early newborn period. This is the first study to show beneficial cognitive effects of uridine in rats with brain damage.Item Neonatal sıçanlarda hipoksik-iskemik infarkt üzerine NMDA reseptör antagonistleri ile hipoterminin nöron koruyucu etkilerinin araştırılması(Uludağ Üniversitesi, 1996) Alkan, Tülin; Özlük, Kasım; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Fizyoloji Anabilim Dalı.Iskemik nöronal harabiyetin ortaya çıkmasındaki majör mekanizmanın glutamatla ortaya çıkarılan eksitotoksisite olduğu kabul edilmektedir. Glutamerjik etkiyi değiştirdiği gösterilen serebral korunma yöntemlerinden N-metil-D-aspartat reseptör antagonisti MK801 ve hafif hipoterminin (30-32 °C) etkileri yenidoğan hipoksik-iskemik beyin modelinde araştırılmıştır. Çalışmamızda isofloran anestezisi altında, 7 günlük ağırlığı 12 g’dan büyük sıçanlara sağ arteria karotis kommunis oklüzyonunu takiben %8 O2 + %92 N2O, 500 mİ cam fanus içinde her bir gruptan birer tane olmak üzere aynı anda iki deneğe 120 dakika süreyle solutuldu. MK801 (0.5 mg/kg sk deneyin 45. ve 120. dakikasında) veya tuzlu su, normotermik (34-36 °C) ve hipotermik (30-32 °C) gruplara verildi. Hipotermiye arteria karotis kommunis ligasyonundan sonra başlanıldı ve hipoksik periyodun sonuna kadar devam edildi. Intrahemisferik sıcaklık, sağ serebral hemisferin içine lambdoid süturun 2 mm anterior, 2 mm lateralinden 2 mm derinliğine yerleştirilen sıcaklık probu ile devamlı olarak ölçüldü ve 15 dakika aralarla kaydedildi. Hipoksik-iskemik beyin harabiyetinden 3 gün sonra tüm denekler öldürülerek beyinleri çıkarıldı. Bregmanın 2 mm anterior ve posteriorundan koronal kesitler alınarak infarkt alanlarının belirlenmesi için 2,3,5- Triphenyltetrazolium Chloride (TTC) ile boyandı. Beyin kesitlerinin slayt çekimlerinden sonra kağıt üzerine projekte edilerek infarkt alanları işaretlendi ve infarkt volümleri kompüter analiz yöntemi ile hesaplandı. Nöronal hasarlanmanın ağırlığı, hipokampustan alınan kesitlerden histolojik olarak Hematoksilen Eosinle (H&E) boyanarak değerlendirildi. Korpus striatumdaki doku harabiyetini saptamak için HPLC yöntemi ile dopamin (DA) ve dihidroksifenilasetik asit (DOPAC) ölçümleri yapıldı. I. ve II. koronal kesitlerde sadece normotermik grupta infarkt alanı saptandı ve diğer gruplardan istatistiksel olarak anlamlı oranda farklı bulundu (p<0.0001). Nöropatolojik değerlendirme ve striatal doku DA ve DOPAC seviyeleri de yoğun nöronal harabiyeti kanıtladı. MK801 ve hipoterminin tek başlarına uygulandıklarında benzer nöron koruyucu etkileri olduğu buna karşın birlikte kullanılmalarının daha iyi korunma ortaya çıkarttığı gözlenildi.Item Neuronal protective effects of focal ischemic pre-and/or postconditioning on the model of transient focal cerebral ischemia in rats(Elsevier, 2009-05) Türeyen, Kudret; Taşkapılıoğlu, Mevlüt Özgür; Alkan, Tülin; Gören, Bülent; Şahin, Söner; Taşkapılıoğlu, Özlem; Korfalı, Ender; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0001-5472-9065; AAH-1718-2021; ABB-8161-2020; AAH-1792-2021; AAW-5254-2020; AAK-6623-2020; 25936798300; 6601953747; 6602543716; 8272141000; 23037226400; 7004641343We investigated the neuroprotective effects of pre-and postconditioning on infarct volume in the transient middle cerebral artery occlusion (MCAo) model in rats. Thirty-two male rats were divided into occlusion, preconditioning, postconditioning and both pre- and postconditioning groups. MCAo (120 minutes) was monitored with continuous cerebral tissue oxygen (O-2) pressure (PtiO(2)). Pre-conditioning comprised 10 minutes of MC-Ao, 24 hours prior to the 120 minute MCAo. The postconditioning algorithm was 30 seconds of reperfusion followed by 30 seconds of MCAo. This cycle was repeated 3 times at the onset of reperfusion. Comparison of infarct volumes showed a significant difference between the conditioned groups and occlusion group. Although there was better protection in the preconditioning group compared with the other two conditioned groups, the results did not reach statistically significant levels. The results suggest that preconditioning, postconditioning and pre/post conditioning have protective effects on cerebral ischemia.Item Neuroproctective effects of ischemic tolerance (preconditioning) and postconditioning(Türk Nöroşirürji Derneği, 2009-10) Alkan, Tülin; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0001-6466-5042; AAH-1792-2021; 6601953747Elucidation of the endogenous cell survival pathways involved in ischemic tolerance (preconditioning) and postconditioning has significant clinical implications for preventing neuronal damage in susceptible patients. Ischemic tolerance is a phenomenon in which the brain protects itself against future injury by adapting to low doses of noxious insults. Ischemic postconditioning is defined as brief periods of reperfusion alternating with re-occlusion applied during the very early minutes of reperfusion that mechanically alters the hydrodynamics of reperfusion. Similar pathways and molecules play a role in pre-and postconditioning but their roles and timing are different in each conditioning. Understanding the neuroprotective effects of mechanisms underlying conditionings has been elusive, but NNMA receptor activation, nitric oxide, inflammatory cytokines, and suppression of the innate immune system appear to have a role. Reactive oxygen species and classical ligand stimuli play a role in postconditioning with KATP channels and protein kinase C pathways acting as mediators.Item Neuroprotective effects of melatonin administered alone or in combination with topiramate in neonatal hypoxic-ischemic rat model(IOS Press, 2012) Özyener, Fadıl; Çetinkaya, Merih; Alkan, Tülin; Gören, Bülent; Kafa, İlker Mustafa; Kurt, Mustafa Ayberk; Köksal, Nilgün; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı/Neonatoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; 0000-0002-4606-6596; 0000-0003-3368-8123; AAH-1792-2021; AAH-1718-2021; AAG-8393-2021; AAH-1641-2021; AAG-7125-2021; AAR-4341-2020; 6506242143; 23994946300; 6601953747; 6602543716; 8450193200; 35603735000; 7003323615Purpose: The objective of this study was to compare the effects of two neuroprotective agents; melatonin, a free radical scavenger and topiramate, AMPA/kainate receptor antagonist, administered alone or in combination in neonatal hypoxic-ischemic model. Methods: After being anesthetized, 7-day-old pups underwent ischemia followed by exposure to hypoxia. The pups were divided into 4 groups in order to receive the vehicle, melatonin, topiramate and combination of topiramate and melatonin. These were administered intraperitoneally for three times; the first before ischemia, the second after hypoxia and the third 24 hours after the second dose. After sacrification, infarct volume and apoptosis were evaluated. Results: Percent infarcted brain volume was significantly reduced in rats which received drugs compared with those which received the vehicle. The number of TUNEL positive cells per unit area in hippocampus and cortex were markedly reduced in drug treated groups compared with control group. No significant differences were found regarding percent infarcted brain volume and number of TUNEL positive cells among drug-treated groups. Conclusions: Melatonin and topiramate, administered either alone or in combination significantly reduced the percent infarcted brain volume and number of TUNEL positive cells suggesting that these agents may confer benefit in treatment of infants with hypoxic-ischemic encephalopathy.Item Neuroprotective effects of postconditioning on lipid peroxidation and apoptosis after focal cerebral ischemia/reperfusion injury in rats(Türkiye Nöroşirürji Derneği, 2010-01) Abaş, Faruk; Alkan, Tülin; Gören, Bülent; Taşkapılıoğlu, Özgür; Sarandöl, Emre; Tolunay, Şahsine; Uludağ Üniversitesi/Tıp Fakültesi/Beyin ve Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; 0000-0002-2593-7196; ABE-1716-2020; AAH-1718-2021; ABB-8161-2020; AAH-1792-2021; 8546184300; 6601953747; 6602543716; 6506852772; 55943324800; 6602604390AIM: Apoptosis after cerebral ischemia/reperfusion (I/R) injury leads to the process of cell death. The deal therapeutic approach would target the apoptosis after I/R. Ischemic postconditioning is a recently discovered neuroprotective strategy that involves the application of brief mechanical reperfusion with a specific algorithm at the onset of reperfusion following an ischemic period. MATERIAL and METHODS: Transient MCAo was performed on male SD (275 +/- 25g) rats with intraluminal thread insertion for 2hrs. Rats (n:36) were treated with postconditioning after 60 minutes of occlusion. The postconditioning algorithm was 30 secs of brief reperfusion followed by 30 secs of MCAo and this cycle was repeated 3 times at the onset of reperfusion. RESULTS: After I/R injury, % change of the malonyldialdehyde (MDA) levels in the cortex, which is an index of lipid peroxidation, was found significantly higher in the I/R group. On the other hand postconditioning upregulated Bcl-2 and Bax translocation to the mitochondria, and caspase-3 activity and also reduced oxidative stress levels. CONCLUSION: These findings indicated this neuroprotective effect is most likely achieved by antiapoptotic mechanisms through caspase pathways.Item Neuroprotective effects of uridine in a rat model of neonatal hypoxic-ischemic encephalopathy(Elsevier Ireland, 2013-05) Cansev, Mehmet; Minbay, Zehra; Gören, Bülent; Yaylagül, Esra Örenlili; Çetinkaya, Merih; Köksal, Nilgün; Alkan, Tülin; Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Neonatoloji Anabilim Dalı.; 0000-0001-6466-5042; 0000-0002-5206-1185; 0000-0002-5206-1185; 0000-0001-5757-8450; AAH-1792-2021; AAH-1718-2021; ABC-1475-2020; AAG-8393-2021; V-4209-2018; M-9071-2019; ABH-4915-2020; 8872816100; 8220935200; 6602543716; 55618956600; 23994946300; 7003323615; 6601953747Neonatal hypoxic ischemic encephalopathy (HIE) is a major cause of neurological disability requiring newer therapeutic strategies. Uridine is the principal circulating pyrimidine in humans and a substrate for nucleotides and membrane phospholipids. The objective of this study was to investigate the effects of uridine in a neonatal rat model of HIE. Rat pups subjected to hypoxic ischemic insult on postnatal day 7 were injected intraperitoneally with either saline or uridine (100, 300 or 500 mg/kg) for three consecutive days and brains were collected for evaluation of brain infarct volume and apoptosis. Compared with Control group, uridine at 300 and 500 mg/kg doses significantly reduced percent infarct volume, TUNEL(+) cell ratio and active Caspase-3 immunoreactivity in the cortex, as well as in CA1 and CA3 regions of the hippocampus. Uridine (300 and 500 mg/kg) also decreased active Caspase-3 expression in the ipsilateral hemisphere. These data indicate that uridine dose-dependently reduces brain injury in a rat model of neonatal HIE by decreasing apoptosis.