Several accidents such as sport and traffic may induce head trauma for inducing mild traumatic brain injuries. Then the mild traumatic brain injuries result in primary and secondary brain injuries for resulting neurodegenerative disorders. Investigation of the traumatic brain injuries in the subject are difficult due to ethical restrictions. In addition, results of postmortem analyses of mild traumatic brain injuries are not valuable for clarifying the etiology of the mild traumatic brain injuries. Therefore, the animal models have great importance for the clarifying etiology of the mild traumatic brain injuries. Today, there are several animal models of mild traumatic brain injuries such as models of Marmarou, Feeney and Maryland (Marmarou et al. 1994; Hiskens et al. 2019). However, they are severe and acute models instead of the mild traumatic brain injuries. Recently, Dr. Mehmet Bilgen from USA discovered a valuable mechanical technique for the injuries (Bilgen, 2005). This presentation, I aimed to examine the literature for variables included in these animal models. Present data on the experimental traumatic brain injury suggested that appropriate animal models can assist in understanding the pathophysiological outcomes of patients with traumatic brain injury. The animal models could be used for discovering new therapies in the treatment of traumatic brain injuries.
体育、交通等几种事故可诱发头部外伤，引起轻度外伤性脑损伤。然后轻度创伤性脑损伤导致原发性和继发性脑损伤，从而导致神经退行性疾病。由于伦理的限制，对该学科的外伤性脑损伤的调查是困难的。此外，对轻度创伤性脑损伤的死后分析结果对明确轻度创伤性脑损伤的病因没有价值。因此，动物模型的建立对阐明轻度外伤性脑损伤的病因具有重要意义。目前，有几种轻度创伤性脑损伤动物模型，如Marmarou, Feeney和Maryland模型(Marmarou et al. 1994;Hiskens et al. 2019)。然而，它们是严重和急性的模型，而不是轻度的创伤性脑损伤。最近，来自美国的Mehmet Bilgen博士发现了一种治疗损伤的有价值的机械技术(Bilgen, 2005)。这次演讲，我的目的是检查这些动物模型中包含的变量的文献。目前关于实验性创伤性脑损伤的数据表明，适当的动物模型有助于了解创伤性脑损伤患者的病理生理结局。该动物模型可用于探索创伤性脑损伤治疗的新方法。
{"title":"Experimental traumatic brain injury models in rodents","authors":"Özgür Öcal","doi":"10.37212/JCNOS.584693","DOIUrl":"https://doi.org/10.37212/JCNOS.584693","url":null,"abstract":"Several accidents such as sport and traffic may induce head trauma for inducing mild traumatic brain injuries. Then the mild traumatic brain injuries result in primary and secondary brain injuries for resulting neurodegenerative disorders. Investigation of the traumatic brain injuries in the subject are difficult due to ethical restrictions. In addition, results of postmortem analyses of mild traumatic brain injuries are not valuable for clarifying the etiology of the mild traumatic brain injuries. Therefore, the animal models have great importance for the clarifying etiology of the mild traumatic brain injuries. Today, there are several animal models of mild traumatic brain injuries such as models of Marmarou, Feeney and Maryland (Marmarou et al. 1994; Hiskens et al. 2019). However, they are severe and acute models instead of the mild traumatic brain injuries. Recently, Dr. Mehmet Bilgen from USA discovered a valuable mechanical technique for the injuries (Bilgen, 2005). This presentation, I aimed to examine the literature for variables included in these animal models. Present data on the experimental traumatic brain injury suggested that appropriate animal models can assist in understanding the pathophysiological outcomes of patients with traumatic brain injury. The animal models could be used for discovering new therapies in the treatment of traumatic brain injuries.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46171265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tumor cells preferentially use the glycolysis process as a source of ATP regardless of the availability of oxygen (Warburg effect). GBM cells are particularly dependent on this process. A PET diagnostic test using a fluoro-labeled 2-DG derivative indicates that GBM cells accumulate 2-DG in their interior. Unfortunately, therapeutic use of 2-DG is limited due to insufficient pharmacokinetic parameters of the compound. However, a chemical modification involving the substitution of -OH groups with acetyl groups leads to an increase in 2-DG permeability across the BBB and its concentrations in GBM cells. Based on previous preliminary results using the O-acetylated 2-DG-2deoxy-3,6-di-O-acetyl-D-glucose derivative (WP1122), we assume that the new halogen (2-BG, 2-IG, 2-CG) and acetyl 2-DG derivatives will be highly cytotoxic to GBM cells. In addition, we anticipate the analysis of a new class of 2-DG derivatives, which may be modulated with ethylbutyrate and VPA, may also modulate the activity of HDAC and thus the expression of genes involved in cell apoptosis. The obtained preliminary results on the in vitro model showed that 2-DG decreases the viability of the U87 and U251 cell lines depending on the dose. The IC50 2-DG is for the following lines: U87-0.6mM, 0.5 mM (46,72h), U251-0.7mM, 0.45mM (48,72h). The percentage of apoptotic cells was evaluated by flow cytometry and cell staining with annexinV and PI. The MTT analysis of WP122 showed that the IC50 is in the cells of U87 line-1.5mM, 0.8mM (48,72h), U2511.25mM, 0.8mM (48,72h). The MTT analyzes of the effects of HDIs: NaBt and VPA determined the IC50 for NaBt: U87-1.48mM, 0.95mM (48,72h), U251-2.1mM, 2mM (48,72h); for VPA: U87-6.2mM, 6.0mM (48,72h), U251-5.3mM, 4.2mM (48,72h). Preliminary studies in the analysis of halo-derivatives interaction with hexokinase allowed to develop a model of expression and obtain a recombinant hexokinase protein, which will then be used for crystallographic analyzes.
{"title":"New derivatives of 2-deoxy-D-glucose (2-DG) in the therapy of glioblastoma multiforme - preliminary studies","authors":"E. Siwiak, M. Sołtyka","doi":"10.37212/JCNOS.584722","DOIUrl":"https://doi.org/10.37212/JCNOS.584722","url":null,"abstract":"Tumor cells preferentially use the glycolysis process as a source of ATP regardless of the availability of oxygen (Warburg effect). GBM cells are particularly dependent on this process. A PET diagnostic test using a fluoro-labeled 2-DG derivative indicates that GBM cells accumulate 2-DG in their interior. Unfortunately, therapeutic use of 2-DG is limited due to insufficient pharmacokinetic parameters of the compound. However, a chemical modification involving the substitution of -OH groups with acetyl groups leads to an increase in 2-DG permeability across the BBB and its concentrations in GBM cells. Based on previous preliminary results using the O-acetylated 2-DG-2deoxy-3,6-di-O-acetyl-D-glucose derivative (WP1122), we assume that the new halogen (2-BG, 2-IG, 2-CG) and acetyl 2-DG derivatives will be highly cytotoxic to GBM cells. In addition, we anticipate the analysis of a new class of 2-DG derivatives, which may be modulated with ethylbutyrate and VPA, may also modulate the activity of HDAC and thus the expression of genes involved in cell apoptosis. The obtained preliminary results on the in vitro model showed that 2-DG decreases the viability of the U87 and U251 cell lines depending on the dose. The IC50 2-DG is for the following lines: U87-0.6mM, 0.5 mM (46,72h), U251-0.7mM, 0.45mM (48,72h). The percentage of apoptotic cells was evaluated by flow cytometry and cell staining with annexinV and PI. The MTT analysis of WP122 showed that the IC50 is in the cells of U87 line-1.5mM, 0.8mM (48,72h), U2511.25mM, 0.8mM (48,72h). The MTT analyzes of the effects of HDIs: NaBt and VPA determined the IC50 for NaBt: U87-1.48mM, 0.95mM (48,72h), U251-2.1mM, 2mM (48,72h); for VPA: U87-6.2mM, 6.0mM (48,72h), U251-5.3mM, 4.2mM (48,72h). Preliminary studies in the analysis of halo-derivatives interaction with hexokinase allowed to develop a model of expression and obtain a recombinant hexokinase protein, which will then be used for crystallographic analyzes.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47921777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calcium ion (Ca2+) is the most prominent secondary messenger of physiological cellular signals and ion channels research (Moeder et al. 2019). Neurotransmission, muscle contraction and fertilization are only a few of the physiological properties that make calcium ion important in most eukaryotic cells (Pharris et al. 2018). The extracellular calcium concentration is 1-3 mM whereas the intracellular concentration is around 80-100 nM. This tremendous difference is tightly controlled by dozens of different ion channels embedded in the membrane (Van Hook et al. 2019). Activation of these channels causes calcium ions to entry into the cell with density gradient. This produce the calcium signal. It is very important to control that prolonged elevation of intracellular calcium concentration due to channelopathies in ion channels due to various nervous system diseases because it activates caspase cascades leading to permanent damage and apoptosis. In this respect, the calcium indicators are unrivaled in terms of taking clear results by photographing all the points in these steps from the stage they were developed to the final stages. The use of these indicators to address the roles of these ion channels in terms of their contribution to the pathogenesis of neurological diseases has been an indispensible method of molecular analysis in recent years (Xu and Dong, 2019). In this presentation, we will discuss the chemical structures of calcium indicators, their contribution to the examination of cellular signaling pathways, their advantages and disadvantages in the investigation of ion channels in neurological diseases.
钙离子(Ca2+)是生理细胞信号和离子通道研究中最突出的次级信使(Moeder et al. 2019)。神经传递、肌肉收缩和受精只是使钙离子在大多数真核细胞中发挥重要作用的几个生理特性(Pharris et al. 2018)。细胞外钙浓度为1-3 mM，而细胞内钙浓度约为80-100 nM。这种巨大的差异受到嵌入膜中的数十种不同离子通道的严格控制(Van Hook et al. 2019)。这些通道的激活导致钙离子以密度梯度进入细胞。这就产生了钙信号。控制由各种神经系统疾病引起的离子通道病变引起的细胞内钙浓度的长期升高是非常重要的，因为它激活了caspase级联反应，导致永久性损伤和细胞凋亡。在这方面，钙指标是无与伦比的，因为它通过拍摄从开发阶段到最后阶段的这些步骤中的所有点来获得清晰的结果。近年来，利用这些指标来解决这些离子通道在神经系统疾病发病机制中的作用已成为分子分析不可或缺的方法(Xu and Dong, 2019)。在本次演讲中，我们将讨论钙指示剂的化学结构，它们对细胞信号通路检测的贡献，以及它们在神经系统疾病离子通道研究中的优缺点。
{"title":"Using fluorescent calcium indicators in neuronal ion channel studies","authors":"B. Çiğ","doi":"10.37212/JCNOS.584674","DOIUrl":"https://doi.org/10.37212/JCNOS.584674","url":null,"abstract":"Calcium ion (Ca2+) is the most prominent secondary messenger of physiological cellular signals and ion channels research (Moeder et al. 2019). Neurotransmission, muscle contraction and fertilization are only a few of the physiological properties that make calcium ion important in most eukaryotic cells (Pharris et al. 2018). The extracellular calcium concentration is 1-3 mM whereas the intracellular concentration is around 80-100 nM. This tremendous difference is tightly controlled by dozens of different ion channels embedded in the membrane (Van Hook et al. 2019). Activation of these channels causes calcium ions to entry into the cell with density gradient. This produce the calcium signal. It is very important to control that prolonged elevation of intracellular calcium concentration due to channelopathies in ion channels due to various nervous system diseases because it activates caspase cascades leading to permanent damage and apoptosis. In this respect, the calcium indicators are unrivaled in terms of taking clear results by photographing all the points in these steps from the stage they were developed to the final stages. The use of these indicators to address the roles of these ion channels in terms of their contribution to the pathogenesis of neurological diseases has been an indispensible method of molecular analysis in recent years (Xu and Dong, 2019). In this presentation, we will discuss the chemical structures of calcium indicators, their contribution to the examination of cellular signaling pathways, their advantages and disadvantages in the investigation of ion channels in neurological diseases.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47827670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abnormalities of intracellular free Ca+2 concentration is caused through activation of mitochondrial membrane depolarization by excessive levels of reactive oxygen species (ROS). In etiology of cerebral ischemia, the abnormalities of intracellular free Ca+2 concentration and excessive productions of ROS play an important role in the pathophysiology of cerebral ischemia (Chinopoulos and Adam-Vizi, 2006). Ca2+ influx occurs through activation of different cation channels. Well-known cations channels in cell membrane are chemical and voltage gated channels. Apart from the well-known cation channels, there is transient receptor potential (TRP) superfamily. The TRP superfamily is containing 28 members in 7 subfamilies in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the wellknown calcium channels. TRPM2 channel is activated by ADP-ribose NAD+. Another member of TRP superfamily is TRPV1 channel and it is activated several stimuli, including capsaicin, heat (≥43 °C) and acidic pH (≤ 6) (Chinopoulos and Adam-Vizi, 2006; Toda et al, 2019). Both channels are also activated by oxidative stress. Recent data indicated protective roles of some drugs on cerebral ischemia in rodents. One of the drug is duloxetine (DULOX) and it reduced the effects of Ca2+ entry and ROS through inhibition of TRPM2 channel (Toda et al. 2019). Another drug is dexmedetomidine (DEX) and it is an important drug for long-term sedation in intensive care patients, because it induces a rapid response. In addition to the intensive care patients, it has been started to use for sedation and analgesia in emergency medicine patients (McMorrow and Abramo, 2012). Recently, the protective role of DEX through inhibition of TRPM2 and TRPV1 channels on experimental cerebral ischemia in rats was reported (Akpinar et al. 2016). In the oral presentation, I discussed novel effects of TRPM2, TRPV1 and oxidative stress on the cerebral ischemia in rodents and human. I concluded that the results of current data suggest that antioxidant drugs such as DEX and DULOX treatments reduce cerebral ischemia-induced oxidative stress and intracellular Ca2+ signaling through inhibition of TRPM2 and TRPV1 channels. It seems to that the exact relationship between TRP channel activation and the drugs in cerebral ischemia still remains to be determined.
{"title":"Involvement of oxidative stress and TRP channels in cerebral ischemia","authors":"H. Armağan","doi":"10.37212/JCNOS.584688","DOIUrl":"https://doi.org/10.37212/JCNOS.584688","url":null,"abstract":"Abnormalities of intracellular free Ca+2 concentration is caused through activation of mitochondrial membrane depolarization by excessive levels of reactive oxygen species (ROS). In etiology of cerebral ischemia, the abnormalities of intracellular free Ca+2 concentration and excessive productions of ROS play an important role in the pathophysiology of cerebral ischemia (Chinopoulos and Adam-Vizi, 2006). Ca2+ influx occurs through activation of different cation channels. Well-known cations channels in cell membrane are chemical and voltage gated channels. Apart from the well-known cation channels, there is transient receptor potential (TRP) superfamily. The TRP superfamily is containing 28 members in 7 subfamilies in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the wellknown calcium channels. TRPM2 channel is activated by ADP-ribose NAD+. Another member of TRP superfamily is TRPV1 channel and it is activated several stimuli, including capsaicin, heat (≥43 °C) and acidic pH (≤ 6) (Chinopoulos and Adam-Vizi, 2006; Toda et al, 2019). Both channels are also activated by oxidative stress. Recent data indicated protective roles of some drugs on cerebral ischemia in rodents. One of the drug is duloxetine (DULOX) and it reduced the effects of Ca2+ entry and ROS through inhibition of TRPM2 channel (Toda et al. 2019). Another drug is dexmedetomidine (DEX) and it is an important drug for long-term sedation in intensive care patients, because it induces a rapid response. In addition to the intensive care patients, it has been started to use for sedation and analgesia in emergency medicine patients (McMorrow and Abramo, 2012). Recently, the protective role of DEX through inhibition of TRPM2 and TRPV1 channels on experimental cerebral ischemia in rats was reported (Akpinar et al. 2016). In the oral presentation, I discussed novel effects of TRPM2, TRPV1 and oxidative stress on the cerebral ischemia in rodents and human. I concluded that the results of current data suggest that antioxidant drugs such as DEX and DULOX treatments reduce cerebral ischemia-induced oxidative stress and intracellular Ca2+ signaling through inhibition of TRPM2 and TRPV1 channels. It seems to that the exact relationship between TRP channel activation and the drugs in cerebral ischemia still remains to be determined.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44560176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The failure of all the clinical trials focused on the treatment of Alzheimer’s disease (AD), including the Phase 3 aducanumab trial, is another warning that the field must take a different approach. Some authors have already called for a rejection of the amyloid hypothesis, new and old players like tau-related pathology microglia activation and neuroinflammation are now looming on the horizon, but the core of the issue is that the reductionist approach that has dominated modern medicine should be abandoned. We need an epistemological leap forward, a change in paradigm, and an embrace of a complex view of the disease as a condition resulting from the converging failure of many health-controlling systems and networks, a condition that is shaped, in each subject, by the combination of the individual “omic” lookout and its modulation by the environment. Moreover, we need to leave behind the illusion that a single bullet/intervention can be the cure and adopt a systems-biology approach (Greene and Loscalzo, 2017). The talks will discuss the multifactorial nature of AD, a condition in which, along with Aβ accumulation, the convergence of many genetic, environmental, vascular, metabolic, and inflammatory factors promotes the neurodegenerative process. All these conditions find fertile ground, inside and outside of the central nervous system, provided by the aging process. In that respect, converging approaches targeting co-morbidity factors represent one of the more promising areas of intervention as, at least, we need to remind ourselves that a third of AD cases are strongly dependent on the concerted activity of modifiable factors like low education, midlife hypertension, midlife obesity, diabetes, physical inactivity, smoking, and depression (Brem and Sensi 2018). Thus, in line with a more modern, we need to reconcile ourselves to the fact that complex, nontransmissible chronic conditions must be treated with a multifaceted approach.
{"title":"Alzheimer’s disease, the road ahead","authors":"S. Sensi","doi":"10.37212/JCNOS.584665","DOIUrl":"https://doi.org/10.37212/JCNOS.584665","url":null,"abstract":"The failure of all the clinical trials focused on the treatment of Alzheimer’s disease (AD), including the Phase 3 aducanumab trial, is another warning that the field must take a different approach. Some authors have already called for a rejection of the amyloid hypothesis, new and old players like tau-related pathology microglia activation and neuroinflammation are now looming on the horizon, but the core of the issue is that the reductionist approach that has dominated modern medicine should be abandoned. We need an epistemological leap forward, a change in paradigm, and an embrace of a complex view of the disease as a condition resulting from the converging failure of many health-controlling systems and networks, a condition that is shaped, in each subject, by the combination of the individual “omic” lookout and its modulation by the environment. Moreover, we need to leave behind the illusion that a single bullet/intervention can be the cure and adopt a systems-biology approach (Greene and Loscalzo, 2017). The talks will discuss the multifactorial nature of AD, a condition in which, along with Aβ accumulation, the convergence of many genetic, environmental, vascular, metabolic, and inflammatory factors promotes the neurodegenerative process. All these conditions find fertile ground, inside and outside of the central nervous system, provided by the aging process. In that respect, converging approaches targeting co-morbidity factors represent one of the more promising areas of intervention as, at least, we need to remind ourselves that a third of AD cases are strongly dependent on the concerted activity of modifiable factors like low education, midlife hypertension, midlife obesity, diabetes, physical inactivity, smoking, and depression (Brem and Sensi 2018). Thus, in line with a more modern, we need to reconcile ourselves to the fact that complex, nontransmissible chronic conditions must be treated with a multifaceted approach.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44164638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxidative stress induces excessive production of reactive oxygen species (ROS). ROS are including several free oxygen radicals such as singlet oxygen and superoxide radical. Excessive ROS production induces injuries of lipids, nucleic acids and proteins in several cells. Brain and neurons have a high amount of polyunsaturated fatty acids (PUFAs) and consumption of oxygen, but they have low level of antioxidant. Oxidative stress is controlled by several enzymatic and non-enzymatic antioxidants. One of the main nonenzymatic antioxidant is melatonin. Melatonin is secreted from the pineal gland by physiological circadian cycles. It has several physiological functions such as mediator of circannual reproductive rhythms (Tamtaji et al. 2019). However, it has also a regulatory role in the pathophysiological pathways of traumatic brain injury (TBI) in human and rodents (Barlow et al. 2019). TBI is one of the most common causes of the mortalities. Secondary events occur after primary events like shearing of nerve cells and blood vessels, cause posttraumatic neurodegenerations with an increase in ROS and ROS-mediated lipid peroxidation. It was reported that TBI-induced oxidative stress in experimental TBI was inhibited by the melatonin treatment (Senol and Naziroglu, 2014). Results of a recent study indicated protective role of melatonin through inhibition of Nrf2 signaling pathway, inflammation and oxidative stress in TBI-induced mice (Wang et al. 2019). In human studies, behavioral outcomes of TBI were modulated by the melatonin treatment (Barlow et al. 2019). In the oral presentation, I will review recent studies on TBI in human and experimental animals. In conclusion, there are pre-clinical and clinical evidences that melatonin treatment after TBI significantly improves both behavior-cognition outcomes and pathophysiological outcomes such as oxidative stress and inflammation. It seems that the certain interaction between melatonin and TBI still remain to be determined.
{"title":"Potential therapeutic role of melatonin in traumatic brain injury: A literature review","authors":"Kemal Ertilav","doi":"10.37212/JCNOS.584703","DOIUrl":"https://doi.org/10.37212/JCNOS.584703","url":null,"abstract":"Oxidative stress induces excessive production of reactive oxygen species (ROS). ROS are including several free oxygen radicals such as singlet oxygen and superoxide radical. Excessive ROS production induces injuries of lipids, nucleic acids and proteins in several cells. Brain and neurons have a high amount of polyunsaturated fatty acids (PUFAs) and consumption of oxygen, but they have low level of antioxidant. Oxidative stress is controlled by several enzymatic and non-enzymatic antioxidants. One of the main nonenzymatic antioxidant is melatonin. Melatonin is secreted from the pineal gland by physiological circadian cycles. It has several physiological functions such as mediator of circannual reproductive rhythms (Tamtaji et al. 2019). However, it has also a regulatory role in the pathophysiological pathways of traumatic brain injury (TBI) in human and rodents (Barlow et al. 2019). TBI is one of the most common causes of the mortalities. Secondary events occur after primary events like shearing of nerve cells and blood vessels, cause posttraumatic neurodegenerations with an increase in ROS and ROS-mediated lipid peroxidation. It was reported that TBI-induced oxidative stress in experimental TBI was inhibited by the melatonin treatment (Senol and Naziroglu, 2014). Results of a recent study indicated protective role of melatonin through inhibition of Nrf2 signaling pathway, inflammation and oxidative stress in TBI-induced mice (Wang et al. 2019). In human studies, behavioral outcomes of TBI were modulated by the melatonin treatment (Barlow et al. 2019). In the oral presentation, I will review recent studies on TBI in human and experimental animals. In conclusion, there are pre-clinical and clinical evidences that melatonin treatment after TBI significantly improves both behavior-cognition outcomes and pathophysiological outcomes such as oxidative stress and inflammation. It seems that the certain interaction between melatonin and TBI still remain to be determined.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41554548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NMDA receptor (NMDAR) overstimulation by glutamate promotes massive calcium (Ca2+) entry and initiates a cascade of events leading to the overproduction of Reactive Oxygen Species (ROS), mitochondrial dysfunction, intraneuronal zinc (Zn2+) mobilization, and, ultimately, neuronal demise (Choi 1992). This glutamate-driven form of neuronal death has been described as excitotoxicity (Olney 1969). NADPH-diaphorase neurons [nNOS (+) neurons] are a subpopulation of nitric-oxide synthase-overexpressing interneurons that is spared from the NMDAR-mediated neuronal death (Koh and Choi, 1988). The mechanisms underlying the reduced vulnerability of nNOS (+) neurons to NMDAR-driven neuronal death are still largely unexplored. In the talk, we will discuss the mechanisms that are involved in the reduced vulnerability of nNOS (+) neurons. Differences between nNOS (+) and nNOS (-) neurons as far as changes in intracellular Ca2+ levels, mitochondrial functioning, ROS production as well as the intraneuronal accumulation of Zn2+ were investigated. We found that nNOS (+) neurons differ from nNOS (-) cells by lacking the production of a significant amount of ROS in response to NMDAR activation. The absence of NMDA-driven oxidative stress shown by the nNOS (+) neurons abolished the neurotoxic accumulation of Zn2+. Exposure of nNOS (-) neurons to NMDA in the presence of TPEN (a Zn2+ chelator) mimicked the behavior of the nNOS (+) subpopulation and preserved the nNOS (-) population from the excitotoxic damage. These results indicate that Zn2+ mobilization is the mandatory step of the excitotoxic cascade. These findings identify the intraneuronal accumulation of Zn2+ as a therapeutic target for the treatment of excitotoxic prone neurological conditions.
{"title":"Intracellular zinc mobilization is required for nNOS (+) neuron loss. Role of zinc in the excitotoxic cascade","authors":"A. Granzotto","doi":"10.37212/JCNOS.584662","DOIUrl":"https://doi.org/10.37212/JCNOS.584662","url":null,"abstract":"NMDA receptor (NMDAR) overstimulation by glutamate promotes massive calcium (Ca2+) entry and initiates a cascade of events leading to the overproduction of Reactive Oxygen Species (ROS), mitochondrial dysfunction, intraneuronal zinc (Zn2+) mobilization, and, ultimately, neuronal demise (Choi 1992). This glutamate-driven form of neuronal death has been described as excitotoxicity (Olney 1969). NADPH-diaphorase neurons [nNOS (+) neurons] are a subpopulation of nitric-oxide synthase-overexpressing interneurons that is spared from the NMDAR-mediated neuronal death (Koh and Choi, 1988). The mechanisms underlying the reduced vulnerability of nNOS (+) neurons to NMDAR-driven neuronal death are still largely unexplored. In the talk, we will discuss the mechanisms that are involved in the reduced vulnerability of nNOS (+) neurons. Differences between nNOS (+) and nNOS (-) neurons as far as changes in intracellular Ca2+ levels, mitochondrial functioning, ROS production as well as the intraneuronal accumulation of Zn2+ were investigated. We found that nNOS (+) neurons differ from nNOS (-) cells by lacking the production of a significant amount of ROS in response to NMDAR activation. The absence of NMDA-driven oxidative stress shown by the nNOS (+) neurons abolished the neurotoxic accumulation of Zn2+. Exposure of nNOS (-) neurons to NMDA in the presence of TPEN (a Zn2+ chelator) mimicked the behavior of the nNOS (+) subpopulation and preserved the nNOS (-) population from the excitotoxic damage. These results indicate that Zn2+ mobilization is the mandatory step of the excitotoxic cascade. These findings identify the intraneuronal accumulation of Zn2+ as a therapeutic target for the treatment of excitotoxic prone neurological conditions.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43801423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cisplatin (CSP) is used treatment of several cancers. However, it has also adverse effect through excessive reactive oxygen species production and activation of TRPV1 channel activation in neurons. Pregabalin (PGAB) has antioxidant and calcium channel blocker actions in neurons. I have investigated protective role of PGAB against the adverse effects of CSP in DBTRG neuronal cells. The neuronal cells were divided into four groups as control group, PGAB group (500 M for 24 1 hrs), CSP group (25 M for 24 hrs), and PGAB+CSP combination group. CISP-induced decrease of cell viability, glutathione peroxidase and glutathione level in the cells were increased in the neurons by PGAB treatment. However, CSP-induced increase of apoptosis, Ca2+ fluorescence intensity, TRPV1 current densities through the increase mitochondrial oxidative stress were decreased in the neurons by PGAB treatment. In conclusion, CSP-induced increases in mitochondrial ROS and cell death levels in the neuronal cells were decreased through the decrease of TRPV1 activation with the effect of PGAB treatment. CSP-induced drug resistance in the neurons might be reduced by PGAB treatment.
{"title":"Pregabalin protected cisplatin-induced oxidative neurotoxicity in neuronal cell line","authors":"Kemal Ertilav","doi":"10.37212/jcnos.653500","DOIUrl":"https://doi.org/10.37212/jcnos.653500","url":null,"abstract":"Cisplatin (CSP) is used treatment of several cancers. However, it has also adverse effect through excessive reactive oxygen species production and activation of TRPV1 channel activation in neurons. Pregabalin (PGAB) has antioxidant and calcium channel blocker actions in neurons. I have investigated protective role of PGAB against the adverse effects of CSP in DBTRG neuronal cells. The neuronal cells were divided into four groups as control group, PGAB group (500 M for 24 1 hrs), CSP group (25 M for 24 hrs), and PGAB+CSP combination group. CISP-induced decrease of cell viability, glutathione peroxidase and glutathione level in the cells were increased in the neurons by PGAB treatment. However, CSP-induced increase of apoptosis, Ca2+ fluorescence intensity, TRPV1 current densities through the increase mitochondrial oxidative stress were decreased in the neurons by PGAB treatment. In conclusion, CSP-induced increases in mitochondrial ROS and cell death levels in the neuronal cells were decreased through the decrease of TRPV1 activation with the effect of PGAB treatment. CSP-induced drug resistance in the neurons might be reduced by PGAB treatment.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45355573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yusuf Karagozoglu, A. E. Parlak, N. Alayunt, S. Turkoglu, I. Yıldırım, M. Karatepe
In this study, effects of hydroxyurea derivatives 1, 3, 4 - thiadiazole and schiff base compounds on some element levels and antioxidant enzyme activities in rat liver and on antioxidant enzyme levels that are parameters of oxidative stress were investigated. For this purpose, iron (Fe), zinc (Zn) and copper (Cu) concentrations were analyzed by using atomic absorption spectroscopy superoxide dismutase (SOD) and catalase (CAT) activities were measured by using a UV spectrophotometer. Fe, Zn and Cu concentrations in the liver of rats treated with these compounds were compared with levels of SOD and CAT statistically. As a result, the increase in the antioxidant activities of SOD and CAT metalloenzymes together with decrease in levels of Cu, Zn and Fe elements observed may suggest that the elements be bound to these enzymes.
{"title":"Relationship between some element levels and oxidative stress parameters in rats liver treated with hydroxyurea derivative compounds","authors":"Yusuf Karagozoglu, A. E. Parlak, N. Alayunt, S. Turkoglu, I. Yıldırım, M. Karatepe","doi":"10.37212/JCNOS.579145","DOIUrl":"https://doi.org/10.37212/JCNOS.579145","url":null,"abstract":"In this study, effects of hydroxyurea derivatives 1, 3, 4 - thiadiazole and schiff base compounds on some element levels and antioxidant enzyme activities in rat liver and on antioxidant enzyme levels that are parameters of oxidative stress were investigated. For this purpose, iron (Fe), zinc (Zn) and copper (Cu) concentrations were analyzed by using atomic absorption spectroscopy superoxide dismutase (SOD) and catalase (CAT) activities were measured by using a UV spectrophotometer. Fe, Zn and Cu concentrations in the liver of rats treated with these compounds were compared with levels of SOD and CAT statistically. As a result, the increase in the antioxidant activities of SOD and CAT metalloenzymes together with decrease in levels of Cu, Zn and Fe elements observed may suggest that the elements be bound to these enzymes.","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41756741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The amplitude-frequency characteristics of the late and early components of brain- evoked potentials (EP) and the speed of motor (MK), central ( central information processing (CIP ) and sensory (SC) component of the reaction of choice 2 from 3 stimuli (RC 2-3 ), presented in mode go/nogo/gо investigated in children, teenagers and young people. It was found that the formation of sensorimotor reactions of differentiation in children, teenagers and young people is characterized by a gradual decrease in the quantities of mistakes and time of RC 2-3 , MK, SC, CIP , also latency and an increase in amplitude the evoked potential ( Е P ) . In children was invented simultaneous activation of the early ( N 1 , Р 1 , N 2 , Р 2 ) and deactivation of late (Р 3 ) Е P of the cerebral cortex and significant more mistakes and lower speed of RC 2-3 , MC, SC, CIP which indicates the presence of cortical-subcortical dysfunction of the sensor-motor system. In young people high speed of RC 2-3 , MC, SC, CIP and a smaller quantities of mistakes coincided with short latencies and a high amplitude of inter- peak intervals N 1 -P 2 and P 2 -N 2 and Р 300 . The results testify the formation of neurophysiological mechanisms of sensory-motor differentiation reactions happens with participation , mainly, of the early (N 1 , P 1 , N 2 , P 2 ) component s of children whereas late components of the Е P (P 3 ) are more actively involved in young people .
{"title":"Neurophysiological Mechanisms of Regulation of Sensomotor Reactions of Differentiation in Onthogenesis","authors":"A. Palabiyik, V. S. Lizohub, N. Chernenko","doi":"10.37212/JCNOS.613330","DOIUrl":"https://doi.org/10.37212/JCNOS.613330","url":null,"abstract":"The amplitude-frequency characteristics of the late and early components of brain- evoked potentials (EP) and the speed of motor (MK), central ( central information processing (CIP ) and sensory (SC) component of the reaction of choice 2 from 3 stimuli (RC 2-3 ), presented in mode go/nogo/gо investigated in children, teenagers and young people. It was found that the formation of sensorimotor reactions of differentiation in children, teenagers and young people is characterized by a gradual decrease in the quantities of mistakes and time of RC 2-3 , MK, SC, CIP , also latency and an increase in amplitude the evoked potential ( Е P ) . In children was invented simultaneous activation of the early ( N 1 , Р 1 , N 2 , Р 2 ) and deactivation of late (Р 3 ) Е P of the cerebral cortex and significant more mistakes and lower speed of RC 2-3 , MC, SC, CIP which indicates the presence of cortical-subcortical dysfunction of the sensor-motor system. In young people high speed of RC 2-3 , MC, SC, CIP and a smaller quantities of mistakes coincided with short latencies and a high amplitude of inter- peak intervals N 1 -P 2 and P 2 -N 2 and Р 300 . The results testify the formation of neurophysiological mechanisms of sensory-motor differentiation reactions happens with participation , mainly, of the early (N 1 , P 1 , N 2 , P 2 ) component s of children whereas late components of the Е P (P 3 ) are more actively involved in young people .","PeriodicalId":37782,"journal":{"name":"Journal of Cellular Neuroscience and Oxidative Stress","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49066041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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