The neuroprotective effects of diet restriction preconditioning on cerebral ischemia model on mice

Sağlığımızın devamlılığını korumak için önemli bir olgu olan beslenme, aynı zamanda sağlık için tehdit de oluşturabilmektedir. Beslenmedeki bozukluklar sonucu, çeşitli hastalıklara yakalanma riskleri arttığı gibi varolan patofizyolojik süreçler de etkilenebilmektedir. Bu hastalıklardan biri de günümüzde dünya ölüm sıralamalarında ilk üçte yer alan beyin felcidir. Bu çalışmada, kısa dönemli diyet kısıtlamasının fare beyin felci modelindeki, hasar alanı, ödem, nöronal sağkalım ve apoptotik hücre ölümüne olan etkileri incelenmiştir. Bu çalışmada etik kurulu alınmış (karar no:35/2017), 90 ve 30 dakikalık (sırasıyla 24 ve 72 saat reperfüzyon) orta serebral arter tıkanması modeli uygulanan 8-12 haftalık erkek BALB/c fareler kullanılmıştır. Fareler operasyondan üç gün önce gruplarına göre hazırlanmış %70 yoğunluktaki (n=7; protein, yağ, karbonhidrat) diyetlerle beslenmişlerdir. Kontrol grubu standart yemle beslenmeye devam ederken, açlık grubunun yemleri çekilerek sadece suya erişimine izin verilmiştir. İstatistik olarak one-way ANOVA yöntemi kullanılmıştır. Yüksek yağlı diyetle beslenen hayvanlarda, 90 ve 30 dakika iskemideki Laser Doppler flowmetri kayıtlarında, kontrol ve diğer gruplara göre hipoperfüzyon gözlenmiştir. Buna ilaveten 90 dakika iskemide yüksek yağlı diyetle beslenen hayvanlarda kontrol grubuna kıyasla beyindeki hasarın ve ödemin anlamlı olarak artmış olduğu görüldü. Hücresel sağkalıma bakıldığında, yüksek yağ ve yüksek karbonhidrat gruplarında kontrol grubuna kıyasla canlı hücre sayısında anlamlı bir azalma izlenmiştir. Bu çalışmada diyet restriksiyonunun fare beyin felci modelindeki etkisi araştırılmıştır. Elde edilen sonuçlar doğrultusunda beslenmenin beyin felci süreçlerini etkilediğini göstermektedir.Nutrition is an important factor in order to maintain our healthy state. However, it can also become a major threat in the cases of malnutrition. Malnutrition affects several pathophysiological processes and also increases susceptibility to a number of diseases. Cerebral ischemia is an example for such diseases and is the third main reason of mortality worldwide. In this study, we examined the effects of short-term diet restriction using a cerebral ischemia model in mice in terms of infarct volume, edema formation, neuronal survival and apoptotic cell death. This study was carried out in 8-12 weeks old BALB/c mice; with the permission from the Medipol University Ethical board (#35/2017). 90 and 30 minutes (followed by 24 and 72 hours of reperfusion, respectively) of middle cerebral artery occlusion were performed. Animals were fed with %70 high density diets (n=7, protein, fat or carbohydrate) three days prior to middle cerebral artery occlusion. The fasting group was given ad libitum access to water only, whereas the control group was fed on standard mice food. The animals that had high-fat diets showed hypoperfusion on the Laser Doppler flowmeter records on both 90 and 30 minutes of middle cerebral artery occlusion when compared with control and the other diet groups. Also, within the same group, the mice that had gone under 90 minutes of occlusion period had increased edema and infarct volume compared with the control group. Furthermore, the decrease in the neuronal survival rates of the high fat and high carbohydrate groups was statistically significant when compared with the control group. This study focuses on the effects of diet restriction on the recovery processes including neuronal survival and apoptotic cell death following cerebral ischemic injury in mice. Our results suggest that nutrition results in differential effects on the recovery processes, and therefore further studies should be conducted to identify the underlying mechanisms of the beneficial effects of dieting

Investigation of the role of REV-ERBA and REV-ERBβ after acute brain injury

Dünyada ölüm nedenleri bakımından ikinci sırada yer alan inmenin insidansı sirkadiyen bir dağılım göstermektedir. Tüm fizyolojik durumlarımızı düzenleyen sirkadiyen ritmin hem inmenin tetiklenmesine hem de inme sonrasında gelişen patofizyolojik süreçlere önemli etkileri bulunmaktadır. Son yıllarda yapılan çalışmalar sirkadiyen ritmin düzenlemesinde ve devam ettirilmesinde görevli olduğu bilinen nükleer reseptörler RevErbα ve RevErbβ'nın (RevErbα/β) patofizyolojik süreçlerde önemli rollerinin olabileceğini göstermektedir. Bu tez kapsamında nükleer reseptörler olan RevErbα/β'nın (lentivirüs aracılığı ile) protein ifadelerinin artırılmasının veya baskılanmasının fare akut iskemi modelindeki etkileri araştırılmıştır. Beyin hasarı sonrası elde edilen beyin dokularından enfarktüs hacmi, beyin ödemi ve kan beyin bariyeri geçirgenliği araştırılmıştır. Ayrıca geniş ölçekli sıvı kromatografisi/kütle spektrometresi aracılı proteomik analizlerle RevErbα/β'nın etkilediği protein profili gösterilmiştir. Protein ifadesi artırılan grupta hasar hacmi, ödem hacmi ve kan beyin bariyeri geçirgenliğinin azaldığı görülmüştür. Tersine, protein ifadesi baskılanan grupta ise, hasar hacmi, ödem hacmi ve kan beyin bariyeri geçirgenliğinin arttığı gözlemlenmiştir. Yapılan proteom analizinde RevErbα/β protein ifadesi artırılan gruplarda 291, baskılanan gruplarda ise 50 farklı proteinin anlatımının istatistiksel olarak anlamlı ölçüde değiştiği gösterilmiştir. Elde edilen sonuçlar, RevErbα/β protein ifadelerinin artırılması veya baskılanmasının iskemik inmenin patofizyolojisi üzerine farklı etkileri olduğunu göstermektedir. Bu tez, TÜBİTAK tarafından 1001 proje kapsamında 219S913 nolu proje tarafından desteklenmiştir.The incidence of stroke, which ranks second in the world in terms of causes of death, shows a circadian distribution. The circadian rhythm, that regulates all our physiological states, has important effects on both the triggering of stroke and the pathophysiological processes that develop after stroke. Recent studies have shown that the nuclear receptors RevErbα and RevErbβ (RevErbα/β), which are known to be involved in the regulation and maintenance of circadian rhythm, may have important roles in pathophysiological processes of stroke. Within the scope of this thesis, the effects of increasing or suppressing the protein expressions of the nuclear receptors RevErbα/β (lentivirus-mediated) in the mouse acute ischemia model were investigated. Infarction volume, cerebral edema and blood brain barrier permeability were investigated from brain tissues obtained from mice after sacrification. In addition, large-scale liquid chromatography/mass spectrometry-mediated proteomic analyses have shown the protein profile affected by RevErbα/β. It was observed that the infarct volume, edema volume and blood brain barrier permeability decreased in the group with increased protein expression. Conversely, in the group with suppressed protein expression was observed that the infarct volume, cerebral edema and blood-brain barrier permeability increased. In the proteome analysis, it was shown that the expression of 291 different proteins changed in the groups whose RevErbα/β protein expression was increased, and in the suppressed groups, the expression of 50 different proteins changed. The results obtained show that increasing or suppressing RevErbα/β protein expressions have different effects on the pathophysiology of ischemic stroke. This thesis was supported by the TUBITAK project No: 219S913 within the scope of the 1001 project

Generalized papular and sclerodermoid eruption: Scleromyxedema

Scleromyxedema (SM) is a rare chronic progressive and highly intractable cutaneous disease with unknown etiology, affecting both genders equally between 30 and 50 years. The disease is characterized with mucin deposits in the skin and/or other organs. In fact it is a clinicopathological subset of lichen myxedematosus (LM) according to a new classification. Sclerodermiform plaques and lichenoid papules are characteristic cutaneous lesions. An elevation of IgG λ (lambda) chain exists in most cases and extracutaneous involvement occurring with variable systemic findings is also detected. Generalized form is quite difficult to treat and may even be fatal. Herein, we present a male patient with typical features of generalized papular and sclerodermoid LM variety and with benign outcome by isotretinoin

The role of ERK pathway in the neuroprotective effect of memantine

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Neuroprotective effect of diet restricted preconditioning on cerebral ischemia in mice

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Normobaric oxygen treatment improves neuronal survival functional recovery and axonal plasticity after newborn hypoxia-ischemia

Background: Newborn hypoxia ischemia (HI) is one of the most prevalent cases in the emergency and can result from fetal hypoxia during delivery. In HI, restricted blood supply to the fetal brain may cause epilepsy or mental disorders.Methods: In the present study, seven-day-old pups were subjected HI and treated with different normobaric oxygen (NBO) concentrations (21%, 70% or 100%). In the acute phase, we analyzed infarct area, disseminate neuronal injury and surviving neurons. In addition, we studied the regulation of PTEN and MMP-9 proteins which were suggested to be activated by HI in the ischemic tissue. Moreover, long-term effects of NBO treatments were evaluated with open field, rotarod and Barnes maze tests. We also examined axonal plasticity with EGFP-AAV injection.Results: Here, we demonstrate that hyperoxic NBO concentration causes an increase in cellular survival and a decrease in the number of apoptotic cells, meanwhile inhibiting the proteins involved in cellular death mechanisms. Moreover, we found that hyperoxia decreases anxiety, promotes motor coordination and improve spatial learning and memory. Notably that axonal sprouting was promoted by hyperoxia.Conclusion: Our data suggest that NBO is a promising approach for the treatment of newborn HI, which encourage proof-of-concept studies in newborn.Turkish Academy of Sciences Necmettin Erbakan Universit

The effect of Oatp1a5 on drug accumulation and injury upon ischemic stroke

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Effects of repetitive transcranial magnetic stimulation on motor activity and neuronal survival after spinal cord injury

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Cinnamon polyphenol extract exerts neuroprotective activity in traumatic brain injury in male mice

WOS: 000441417400005PubMed ID: 29714150Introduction: Cinnamon polyphenol extract is a traditional spice commonly used in different areas of the world for the treatment of different disease conditions which are associated with inflammation and oxidative stress. Despite many preclinical studies showing the anti-oxidative and anti-inflammatory effects of cinnamon, the underlying mechanisms in signaling pathways via which cinnamon protects the brain after brain trauma remained largely unknown. However, there is still no preclinical study delineating the possible molecular mechanism of neuroprotective effects cinnamon polyphenol extract in Traumatic Brain Injury (TBI). The primary aim of the current study was to test the hypothesis that cinnamon polyphenol extract administration would improve the histopathological outcomes and exert neuroprotective activity through its antioxidative and anti-inflammatory properties following TBI. Methods: To investigate the effects of cinnamon, we induced brain injury using a cold trauma model in male mice that were treated with cinnamon polyphenol extract (10 mg/kg) or vehicle via intraperitoneal administration just after TBI. Mice were divided into two groups: TBI+vehicle group and TBI+ cinnamon polyphenol extract group. Brain samples were collected 24 h later for analysis. Results: We have shown that cinnamon polyphenol extract effectively reduced infarct and edema formation which were associated with significant alterations in inflammatory and oxidative parameters, including nuclear factor-KB, interleukin 1-beta, interleukin 6, nuclear factor erythroid 2-related factor 2, glial fibrillary acidic protein, neural cell adhesion molecule, malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase. Conclusion: Our results identify an important neuroprotective role of cinnamon polyphenol extract in TBI which is mediated by its capability to suppress the inflammation and oxidative injury. Further, specially designed experimental studies to understand the molecular cross-talk between signaling pathways would provide valuable evidence for the therapeutic role of cinnamon in TBI and other TBI related conditions

Neuroprotective effect of lithium in cold- induced traumatic brain injury in mice

Apart from its well-established therapeutic activity on bipolar disorder and depression, lithium exerts neuroprotective activity upon neurodegenerative disorders, such as traumatic brain injury (TBI). However, the cellular signaling mechanisms mediating lithium's neuroprotective activity and long-term dose- and time-dependent effects on close and remote proximity are largely unknown. Herein, we tested prophylactic and acute effects of lithium (2 mmol/kg) after cold- induced TBI. In both conditions, treatments with lithium resulted in reduced infarct volume and apoptosis. Its acute treatment resulted in the increase of Akt, ERK-1/2 and GSK-3 alpha/beta phosphoylations. Interestingly, its prophylactic treatment instead resulted in decreased phosphorylations of Akt, ERK-1/2, p38, JNK-1 moderately and GSK-3 alpha/beta significantly. Then, we tested subacute (35-day follow-up) role of low (0.2 mmol/kg) and high dose (2 mmol/kg) lithium and revealed that high dose lithium group was the most mobile so the least depressed in the tail suspension test. Anxiety level was assessed by light-dark test, all groups' anxiety levels were decreased with time, but lithium had no effect on anxiety like behavior. When subacute effects of injury and drug treatment were evaluated on the defined brain regions, infarct volume was decreased in the high dose lithium group significantly. In contrast to other brain regions, hippocampal atrophies were observed in both lithium treatment groups, which were significant in the low dose lithium group in both hemispheres, which was associated with the reduced cell proliferation and neurogenesis. Our data demonstrate that lithium treatment protects neurons from TBI. However, long term particularly low-dose lithium causes hippocampal atrophy and decreased neurogenesis.Turkish Academy of Science