Background The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of vascular stiffness, hypertension and accelerated atherosclerosis, which are associated with the metabolic syndrome (MetS) and type 2 diabetes mellitus. In addition to the intima, RAAS plays an important role in vascular media and adventitial remodeling. Methods Descending thoracic aortas of young male transgenic heterozygous (mRen2) 27 (Ren2) rats were utilized for ultrastructural study. This lean model of hypertension, insulin resistance, and oxidative stress harbors the mouse renin gene and is known to have increased aortic tissue levels of angiotensin II, angiotensin type 1 receptors, and elevated plasma aldosterone levels. Results Ultrastructural observations substantiate known and novel findings in the tunica media, internal and external elastic lamina, and tunica adventitia, which includes: increased media collagen - proteoglycan matrix expansion, increased secretory and proliferative activity and migration of vascular smooth muscle cells (VSMCs) into a newly developing subendothelial neointima, increased VSMC caveolae, mitochondria degeneration, apoptosis; and lipid retention at the elastin lamellar interface. Openings in the external elastic lamina allow pericyte-to-VSMC contacts. The tunica adventitia exhibits stromal pericyte hyperplasia with actively synthetic phenotype and pericyte-pericyte connections. Conclusion While these studies only represent a single snapshot in time, they provide an evaluation of early abnormal ultrastructural vascular remodeling in Ren-2 models of the conduit-elastic thoracic aorta.
{"title":"Ultrastructure study of the transgenic REN2 rat aorta – part 2: media, external elastic lamina, and adventitia","authors":"M. Hayden, J. Sowers, V. DeMarco","doi":"10.14748/bmr.v30.6392","DOIUrl":"https://doi.org/10.14748/bmr.v30.6392","url":null,"abstract":"Background The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of vascular stiffness, hypertension and accelerated atherosclerosis, which are associated with the metabolic syndrome (MetS) and type 2 diabetes mellitus. In addition to the intima, RAAS plays an important role in vascular media and adventitial remodeling. Methods Descending thoracic aortas of young male transgenic heterozygous (mRen2) 27 (Ren2) rats were utilized for ultrastructural study. This lean model of hypertension, insulin resistance, and oxidative stress harbors the mouse renin gene and is known to have increased aortic tissue levels of angiotensin II, angiotensin type 1 receptors, and elevated plasma aldosterone levels. Results Ultrastructural observations substantiate known and novel findings in the tunica media, internal and external elastic lamina, and tunica adventitia, which includes: increased media collagen - proteoglycan matrix expansion, increased secretory and proliferative activity and migration of vascular smooth muscle cells (VSMCs) into a newly developing subendothelial neointima, increased VSMC caveolae, mitochondria degeneration, apoptosis; and lipid retention at the elastin lamellar interface. Openings in the external elastic lamina allow pericyte-to-VSMC contacts. The tunica adventitia exhibits stromal pericyte hyperplasia with actively synthetic phenotype and pericyte-pericyte connections. Conclusion While these studies only represent a single snapshot in time, they provide an evaluation of early abnormal ultrastructural vascular remodeling in Ren-2 models of the conduit-elastic thoracic aorta.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85758071","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}
Peripheral nerve injuries occur through three mechanisms, specifically, crush, compression or transection. Disruption of communication between the peripheral and central nervous system follows and leads to motor and sensory deficits. Peripheral nerves in humans have a limited capacity to self-regenerate following injury, which makes nerve transfer the current gold-standard for treatment. Functional nerve regeneration is contingent on several factors ranging from span of injury and the age of the patient. Bioprinted nerve guidance conduits are an emerging candidate for treating peripheral nerve injuries. To optimize the performance of nerve guidance conduits, a firm understanding of neurobiology and the pathophysiology following injury is necessary. This article provides an overview of nerve regeneration and the desirable features when designing a nerve conduit from a neurosurgical perspective.
{"title":"Designing an ideal 3D-bioprint conduit for axonal repair and regeneration: a neurosurgical perspective","authors":"Caleb E. Stewart, C. Kan, D. Nguyen, O. Sulaiman","doi":"10.14748/bmr.v30.6382","DOIUrl":"https://doi.org/10.14748/bmr.v30.6382","url":null,"abstract":"Peripheral nerve injuries occur through three mechanisms, specifically, crush, compression or transection. Disruption of communication between the peripheral and central nervous system follows and leads to motor and sensory deficits. Peripheral nerves in humans have a limited capacity to self-regenerate following injury, which makes nerve transfer the current gold-standard for treatment. Functional nerve regeneration is contingent on several factors ranging from span of injury and the age of the patient. Bioprinted nerve guidance conduits are an emerging candidate for treating peripheral nerve injuries. To optimize the performance of nerve guidance conduits, a firm understanding of neurobiology and the pathophysiology following injury is necessary. This article provides an overview of nerve regeneration and the desirable features when designing a nerve conduit from a neurosurgical perspective.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72631080","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 mesencephalic trigeminal nucleus (Me5) is a unique structure in the central nervous system (CNS), made up of pseudounipolar sensory neurons. It is also a suitable paradigm for studying the plastic alterations in neurons. It is known that the Me5 neurons utilize various neurotransmitters under normal conditions, though little information is available about the morphological and chemical events taking place in the nucleus after injury. This review provides concise description of the structural adaptive changes in Me5 neurons following peripheral axotomy of the masseteric nerve. Furthermore, it validates NADPH-diaphorase activity in them, and using immunohistochemistry for glutamate (Glu), substance P (SP), calcitonin-gene related protein (CGRP), neuropeptide tyrosine (NPY) and galanin (GAL), it deals with the altered neurochemical phenotype of the injured neurons. Our results distinctly show that the Me5 neurons in the rat are extremely sensitive to peripheral injury and we demonstrate their distinct structural and neurochemical plasticity. The adaptive morphological alterations comprise of both qualitative and quantitative alterations in the axotomized Me5 population which are statistically significant when compared with the number and phenotype of the neurons on the contralateral intact side. Besides, the axotomy-induced alterations in the neurochemical character of Me5 are best signified by the down-regulation of the classical neurotransmitters under normal conditions, and the up-regulation of nitric oxide synthase and de novo synthesis of certain neuroactive substances such as NPY, SP, GAL and VIP. It can be inferred that the described phenomena only occur in the nucleus in cases of injury and changes in the environmental cues, and serve as adaptive mechanisms and powerful trophic factors for the neuronal survival in the Me5. There is, undoubtedly, still a long way to go in order to clarify the dynamic and plastic alterations occurring in the CNS in health and disease, and also explain their role in such important functions as pain, perception, learning, cognition and memory.
{"title":"Morphological and neurochemical plasticity of rat mesencephalic trigeminal neurons","authors":"A. Dandov, D. Atanasova, N. Lazarov","doi":"10.14748/bmr.v30.6388","DOIUrl":"https://doi.org/10.14748/bmr.v30.6388","url":null,"abstract":"The mesencephalic trigeminal nucleus (Me5) is a unique structure in the central nervous system (CNS), made up of pseudounipolar sensory neurons. It is also a suitable paradigm for studying the plastic alterations in neurons. It is known that the Me5 neurons utilize various neurotransmitters under normal conditions, though little information is available about the morphological and chemical events taking place in the nucleus after injury. This review provides concise description of the structural adaptive changes in Me5 neurons following peripheral axotomy of the masseteric nerve. Furthermore, it validates NADPH-diaphorase activity in them, and using immunohistochemistry for glutamate (Glu), substance P (SP), calcitonin-gene related protein (CGRP), neuropeptide tyrosine (NPY) and galanin (GAL), it deals with the altered neurochemical phenotype of the injured neurons. Our results distinctly show that the Me5 neurons in the rat are extremely sensitive to peripheral injury and we demonstrate their distinct structural and neurochemical plasticity. The adaptive morphological alterations comprise of both qualitative and quantitative alterations in the axotomized Me5 population which are statistically significant when compared with the number and phenotype of the neurons on the contralateral intact side. Besides, the axotomy-induced alterations in the neurochemical character of Me5 are best signified by the down-regulation of the classical neurotransmitters under normal conditions, and the up-regulation of nitric oxide synthase and de novo synthesis of certain neuroactive substances such as NPY, SP, GAL and VIP. It can be inferred that the described phenomena only occur in the nucleus in cases of injury and changes in the environmental cues, and serve as adaptive mechanisms and powerful trophic factors for the neuronal survival in the Me5. There is, undoubtedly, still a long way to go in order to clarify the dynamic and plastic alterations occurring in the CNS in health and disease, and also explain their role in such important functions as pain, perception, learning, cognition and memory.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74997576","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}
Recent advances have shed light on the relationship between smooth muscle cell (SMC) phenotypic modulation, resolution of inflammation and atherosclerotic plaque stability. The thick fibrous cap covering the lipid core of plaques is composed of bundles of SMC and collagen fibers and few macrophages and lymphocytes, all of which make the plaque resistant to rupture. The thin fibrous cap contains many macrophages and lymphocytes, few SMC and less collagen fibers, all of which may weaken the cap, leaving the plaque vulnerable to rupture. In the present Dance Round, we, at a pharmacotherapeutic level, address the possibility of how the control over the activity of the essential cellular components of the plaque, particularly its fibrous cap, could be implicated in plaque stabilization, focusing on (i) the modulation of SMC from contractile to secretory (fibrogenic) phenotype, (ii) the control on plaque inflammation-resolution processes, and (iii) the reduction of plaque lipid content. Further studies on both unstable plaque and aortic aneurysm, which share a similar, matrix-based vulnerability, may bring new insights for pharmacotherapy of vascular injuries.
{"title":"The fibrous cap: a promising target in the pharmacotherapy of atherosclerosis","authors":"S. Yanev, M. Zhelyazkova-Savova, G. Chaldakov","doi":"10.14748/bmr.v30.6394","DOIUrl":"https://doi.org/10.14748/bmr.v30.6394","url":null,"abstract":"Recent advances have shed light on the relationship between smooth muscle cell (SMC) phenotypic modulation, resolution of inflammation and atherosclerotic plaque stability. The thick fibrous cap covering the lipid core of plaques is composed of bundles of SMC and collagen fibers and few macrophages and lymphocytes, all of which make the plaque resistant to rupture. The thin fibrous cap contains many macrophages and lymphocytes, few SMC and less collagen fibers, all of which may weaken the cap, leaving the plaque vulnerable to rupture. In the present Dance Round, we, at a pharmacotherapeutic level, address the possibility of how the control over the activity of the essential cellular components of the plaque, particularly its fibrous cap, could be implicated in plaque stabilization, focusing on (i) the modulation of SMC from contractile to secretory (fibrogenic) phenotype, (ii) the control on plaque inflammation-resolution processes, and (iii) the reduction of plaque lipid content. Further studies on both unstable plaque and aortic aneurysm, which share a similar, matrix-based vulnerability, may bring new insights for pharmacotherapy of vascular injuries.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77256610","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}
G. Coriale, F. Rosa, G. Battagliese, S. Gencarelli, M. Fiore, G. Ferraguti, M. Vitali, C. Rotondo, M. Messina, M. L. Attilia
The clinical manifestations of alcohol dependence are not homogeneous. Many studies described both cognitive impairments and psychiatric disorders among people with Alcohol use disorder (AUD). However, AUD can be present without comorbid psychiatric disorders or severe cognitive deficits, namely, “pure alcoholics”. Until now, knowledge about effective treatments for this typology of AUD patients remains unknown. The aim of the present study was to assess two psychological methods of intervention: Cognitive-behavioral treatment (CBT) in the short format and the Motivational enhancement therapy (MET). We then opted to compare the efficacy of methods in treating AUD in both men and women pure alcoholics. We performed a controlled and randomized study consisting of 325 people affected by AUD (244 men, 81 women). 72.3% (n=235; 181 men 54 women) were excluded according to selection criteria. The major percentage of exclusion (38.7%; n=91; 63 men 28 women) regarded patients with comorbid psychiatric disorders. Only the 90 remaining test subjects (27.7% of the sample population; 63 men and 27 women) classified as pure alcoholics were eligible for this study. The test subjects were divided into two groups. One group underwent MET (n=47; 35 men and 12 women) and the other underwent CBT (n=43; 28 men and 15 women). We found a significant adherence to the treatment in the CBT group (19 men and 9 women) compared to the MET group (3 men and 1 woman). At the end of treatment, the dropout rates for the CBT and MET therapy groups were 34.9% and 91.5%, respectively. Moreover, we found no differences in the percentage of abstinent days between CBT and MET groups at three months (CBT: n=36; mean 91.40±15.34; MET: n=18; mean 93.90±11.95; t(52)= 0.605, p=0.550), at six months (CBT: N=30; mean 85.00±30.71; MET: n=9; mean 87.78±33.08; t(37)=-0.234, p=0.820) and at twelve months from the beginning of treatment (CBT: n=28; mean 90.14±22.06; MET: n=4; mean 100±0; t(30)=-0.881, p=0.838). In conclusion, we disclose that CBT in the short format could be an effective treatment strategy for pure alcoholics without psychiatric disorders or severe cognitive deficits.
{"title":"Motivational enhancement therapy versus cognitive behavioral therapy in a cohort of men and women with alcohol use disorder","authors":"G. Coriale, F. Rosa, G. Battagliese, S. Gencarelli, M. Fiore, G. Ferraguti, M. Vitali, C. Rotondo, M. Messina, M. L. Attilia","doi":"10.14748/BMR.V30.6393","DOIUrl":"https://doi.org/10.14748/BMR.V30.6393","url":null,"abstract":"The clinical manifestations of alcohol dependence are not homogeneous. Many studies described both cognitive impairments and psychiatric disorders among people with Alcohol use disorder (AUD). However, AUD can be present without comorbid psychiatric disorders or severe cognitive deficits, namely, “pure alcoholics”. Until now, knowledge about effective treatments for this typology of AUD patients remains unknown. The aim of the present study was to assess two psychological methods of intervention: Cognitive-behavioral treatment (CBT) in the short format and the Motivational enhancement therapy (MET). We then opted to compare the efficacy of methods in treating AUD in both men and women pure alcoholics. We performed a controlled and randomized study consisting of 325 people affected by AUD (244 men, 81 women). 72.3% (n=235; 181 men 54 women) were excluded according to selection criteria. The major percentage of exclusion (38.7%; n=91; 63 men 28 women) regarded patients with comorbid psychiatric disorders. Only the 90 remaining test subjects (27.7% of the sample population; 63 men and 27 women) classified as pure alcoholics were eligible for this study. The test subjects were divided into two groups. One group underwent MET (n=47; 35 men and 12 women) and the other underwent CBT (n=43; 28 men and 15 women). We found a significant adherence to the treatment in the CBT group (19 men and 9 women) compared to the MET group (3 men and 1 woman). At the end of treatment, the dropout rates for the CBT and MET therapy groups were 34.9% and 91.5%, respectively. Moreover, we found no differences in the percentage of abstinent days between CBT and MET groups at three months (CBT: n=36; mean 91.40±15.34; MET: n=18; mean 93.90±11.95; t(52)= 0.605, p=0.550), at six months (CBT: N=30; mean 85.00±30.71; MET: n=9; mean 87.78±33.08; t(37)=-0.234, p=0.820) and at twelve months from the beginning of treatment (CBT: n=28; mean 90.14±22.06; MET: n=4; mean 100±0; t(30)=-0.881, p=0.838). In conclusion, we disclose that CBT in the short format could be an effective treatment strategy for pure alcoholics without psychiatric disorders or severe cognitive deficits.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86406622","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}
Traumatic brain injury (TBI) remains a major health challenge and affects the young disproportionately. Accidental and non-accidental TBI in children is a major contributor to morbidity, disability, and death. TBI in this critical period leads to profound neuronal and axonal degeneration followed by cognitive, psychological and memory impairment, altered processing speed, impaired executive functions, emotional liability as well as word finding difficulties. Cognitive and behavioral changes may remain unrecognized for periods even after sustaining mild injury. Although accidental and non-accidental inflicted injury (blunt force or violent shaking-inflicting brain injury or “Shaken baby” syndrome) posits a major clinical and sociological problem, mechanisms of tissue degeneration might be largely similar. The scope of this review will be the experimental research related to modeling blunt (concussive) head trauma specifically to the infant rodent brain resulting in acute (early) and protracted (late) degenerative changes such as axonal degeneration and apoptotic neuronal cell death. Similarly, discussion will be limited to therapeutic windows and potentials for ameliorating the development of early brain injury.
{"title":"Modeling traumatic brain injury: mechanisms of early neuronal and axon degeneration in the infant rodent brain","authors":"K. Dikranian","doi":"10.14748/bmr.v30.6385","DOIUrl":"https://doi.org/10.14748/bmr.v30.6385","url":null,"abstract":"Traumatic brain injury (TBI) remains a major health challenge and affects the young disproportionately. Accidental and non-accidental TBI in children is a major contributor to morbidity, disability, and death. TBI in this critical period leads to profound neuronal and axonal degeneration followed by cognitive, psychological and memory impairment, altered processing speed, impaired executive functions, emotional liability as well as word finding difficulties. Cognitive and behavioral changes may remain unrecognized for periods even after sustaining mild injury. Although accidental and non-accidental inflicted injury (blunt force or violent shaking-inflicting brain injury or “Shaken baby” syndrome) posits a major clinical and sociological problem, mechanisms of tissue degeneration might be largely similar. The scope of this review will be the experimental research related to modeling blunt (concussive) head trauma specifically to the infant rodent brain resulting in acute (early) and protracted (late) degenerative changes such as axonal degeneration and apoptotic neuronal cell death. Similarly, discussion will be limited to therapeutic windows and potentials for ameliorating the development of early brain injury.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80509843","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}
Pamela Rosso, M. Fiore, E. Fico, A. Iannitelli, P. Tirassa
The present study was aimed at evaluating whether single intermittent acute cervical vagus nerve stimulation (ACVS), pro-vided at a frequency which exhibits a clinical efficacy, may influence brain neurotrophins and hippocampal plasticity. With this purpose, the brain of adult male rats undergoing ACVS was used to analyze the expression of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in brain areas known to synthetize these growth factors, and the expression the neural cell adhesion molecule (NCAM), the synaptophysin (SYP) and biosynthetic GABA (GAD67) in the hippocampus. The effects of ACVS on NGF and BDNF protein and mRNA in hippocampus, hypothalamus and cortex two hours after stimulation were shown to be dependent on the frequencies of ACVS stimulation. Prolonged (three days post stimulation) modifications of NGF and BDNF were also observed in the hippocampus of ACVS rats. An early enhancement of the plasticity markers NCAM, SYP and GAD67 was also found in ACVS hippocampus. Three days after stimulation, NCAM and GAD67 levels were still higher than controls. Immunohistochemistry confirms the stimulatory effects of ACVS on GABA showing an increase in GAD67-positive cells in the dentate gyrus and CA3 hippocampal areas. This study shows that ACVS affects brain NGF and BDNF synthesis in a frequency-dependent manner. Neurotrophins changes are associated with increased hippocampal plasticity, as demonstrated by the observed molecular and morphological modifications. These findings support the role of brain neurotrophins in the ACVS mechanism of action.
{"title":"Acute stimulation of vagus nerve modulates brain neurotrophins, and stimulates neuronal plasticity in the hippocampus of adult male rats","authors":"Pamela Rosso, M. Fiore, E. Fico, A. Iannitelli, P. Tirassa","doi":"10.14748/bmr.v30.6391","DOIUrl":"https://doi.org/10.14748/bmr.v30.6391","url":null,"abstract":"The present study was aimed at evaluating whether single intermittent acute cervical vagus nerve stimulation (ACVS), pro-vided at a frequency which exhibits a clinical efficacy, may influence brain neurotrophins and hippocampal plasticity. With this purpose, the brain of adult male rats undergoing ACVS was used to analyze the expression of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in brain areas known to synthetize these growth factors, and the expression the neural cell adhesion molecule (NCAM), the synaptophysin (SYP) and biosynthetic GABA (GAD67) in the hippocampus. The effects of ACVS on NGF and BDNF protein and mRNA in hippocampus, hypothalamus and cortex two hours after stimulation were shown to be dependent on the frequencies of ACVS stimulation. Prolonged (three days post stimulation) modifications of NGF and BDNF were also observed in the hippocampus of ACVS rats. An early enhancement of the plasticity markers NCAM, SYP and GAD67 was also found in ACVS hippocampus. Three days after stimulation, NCAM and GAD67 levels were still higher than controls. Immunohistochemistry confirms the stimulatory effects of ACVS on GABA showing an increase in GAD67-positive cells in the dentate gyrus and CA3 hippocampal areas. This study shows that ACVS affects brain NGF and BDNF synthesis in a frequency-dependent manner. Neurotrophins changes are associated with increased hippocampal plasticity, as demonstrated by the observed molecular and morphological modifications. These findings support the role of brain neurotrophins in the ACVS mechanism of action.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76104591","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}
None of the extant theories of aging have proven to be effective in advancing our knowledge of senescence or mortality. In contrast to the gene-centric focus on evolution, the mechanism of cell-cell interactions as the driving force for evolution as the logic of biology is proposed. Since the distribution of bioenergy over the course of the life cycle is skewed towards the reproductive phase, bioenergy flags in the post-reproductive stage of life, causing failure of cell-cell signaling, loss of homeostatic control, senescence and death. In the interim, the phenotype acts as the ‘agent’ for epigenetic inheritance, obtaining ‘marks’ that inform the organism of changes in the environment. Such marks are inherited by the offspring, providing it with foreknowledge of the environment to come. The organism appears to ‘return’ to the unicellular state over the course of the life cycle, but in reality meiosis is the mechanism of epigenetic inheritance, the adult phenotype being the means for transmitting the epigenetic marks obtained from the environment back to the organism.
{"title":"Cell-cell communication predicts aging, senescence and death: an integrated, predictive evolutionary approach","authors":"J. Torday","doi":"10.14748/bmr.v30.6383","DOIUrl":"https://doi.org/10.14748/bmr.v30.6383","url":null,"abstract":"None of the extant theories of aging have proven to be effective in advancing our knowledge of senescence or mortality. In contrast to the gene-centric focus on evolution, the mechanism of cell-cell interactions as the driving force for evolution as the logic of biology is proposed. Since the distribution of bioenergy over the course of the life cycle is skewed towards the reproductive phase, bioenergy flags in the post-reproductive stage of life, causing failure of cell-cell signaling, loss of homeostatic control, senescence and death. In the interim, the phenotype acts as the ‘agent’ for epigenetic inheritance, obtaining ‘marks’ that inform the organism of changes in the environment. Such marks are inherited by the offspring, providing it with foreknowledge of the environment to come. The organism appears to ‘return’ to the unicellular state over the course of the life cycle, but in reality meiosis is the mechanism of epigenetic inheritance, the adult phenotype being the means for transmitting the epigenetic marks obtained from the environment back to the organism.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75503958","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 prevalence of allergy has increased rapidly over recent years, especially among pediatric patients and it is detected approximately in 2–3% of the world population. Worldwide, respiratory allergic diseases affect nearly 700 million subjects. The pathogenesis of allergy is still poorly understood and is a matter of worldwide concern. It is thought that it results from the interactions between genetic predisposition and excessive and inappropriate immune responses to a large spectrum of environmental risk factors. Recent clinical observations and epidemiological studies have identified associations between nutritional elements (e.g., zinc, and selenium) and allergy prevalence. It is suggested that micronutrients influence the immune system and may play a major role in the development of asthma and in the progression of other allergic diseases. This link is based on the hypothesized benefits of antioxidant functions of certain micronutrients, which may modulate the amount of oxidants in the body. As a result, decrease in oxidative stress may be an important factor in the etiology of childhood asthma. Our aim was to analyze the current literature and to assess whether trace elements level is a risk factor for allergic symptoms in childhood. In this review article, we aimed to describe the properties and biological importance and to define the possible relationship between atopic sensitization and serum levels of zinc and selenium in children. Biomed Rev 2019;30:49-61
{"title":"The role of selenium and zinc in allergic hypersensitization in children","authors":"Halyna Pavlyshyn, Viktoriia Sliiva","doi":"10.14748/bmr.v30.6387","DOIUrl":"https://doi.org/10.14748/bmr.v30.6387","url":null,"abstract":"The prevalence of allergy has increased rapidly over recent years, especially among pediatric patients and it is detected approximately in 2–3% of the world population. Worldwide, respiratory allergic diseases affect nearly 700 million subjects. The pathogenesis of allergy is still poorly understood and is a matter of worldwide concern. It is thought that it results from the interactions between genetic predisposition and excessive and inappropriate immune responses to a large spectrum of environmental risk factors. Recent clinical observations and epidemiological studies have identified associations between nutritional elements (e.g., zinc, and selenium) and allergy prevalence. It is suggested that micronutrients influence the immune system and may play a major role in the development of asthma and in the progression of other allergic diseases. This link is based on the hypothesized benefits of antioxidant functions of certain micronutrients, which may modulate the amount of oxidants in the body. As a result, decrease in oxidative stress may be an important factor in the etiology of childhood asthma. Our aim was to analyze the current literature and to assess whether trace elements level is a risk factor for allergic symptoms in childhood. In this review article, we aimed to describe the properties and biological importance and to define the possible relationship between atopic sensitization and serum levels of zinc and selenium in children. Biomed Rev 2019;30:49-61","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85664685","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}
Genus Cryptosporidium includes around 30 known apicomplexan parasitic species which infect the gastrointestinal tract and rarely the respiratory system of more than 300 vertebrate animals. The immune response against infection by Cryptosporidium spp. includes all strata of innate and adaptive immunity with differences in their significance. The mucosal immunity, expressed predominantly by the “sentinel” role of epitheliocytes, is fundamental to the resistance against an infection (mainly via activation of the TLR4/NF-κB signalling axis). The vast array of epithelial chemokines and cytokines initiate the local inflammatory processes, attract effector cells and may directly suppress the parasite adhesion. The second line of defence includes IFN-γ-production by the NK cells in combination with their innate cytotoxicity against the parasite and the infected epitheliocytes. The adaptive immunity against the parasite depends predominantly on cytotoxic CD4+ Th1-lymphocytes, which makes IFN-γ central to the acquired response too. CD8+ cells aid to some extent the activity of Th1-cells but their involvement is not decisive. While Cryptosporidium infection elicits the synthesis of specific serum and mucosal antibodies, the humoral immunity is of minor importance. In immunocompromised hosts, infants and malnourished children, the mild and usually self-limiting infection can become life-threatening or take a chronic course. It is the second leading cause of fatal diarrhoea in children and one of the major opportunistic pathogens in the continually expanding group of patients with immunodeficiencies and systemic chronic diseases. Unravelling the mechanisms of resistance against Cryptosporidium infection is fundamental for the successful prevention of the disease. Biomed Rev 2019;30:37-48
{"title":"Immunity and resistance to cryptosporidiosis: the intricate ways of an enigmatic parasitosis","authors":"K. Stoyanova, S. Pavlov","doi":"10.14748/bmr.v30.6386","DOIUrl":"https://doi.org/10.14748/bmr.v30.6386","url":null,"abstract":"Genus Cryptosporidium includes around 30 known apicomplexan parasitic species which infect the gastrointestinal tract and rarely the respiratory system of more than 300 vertebrate animals. The immune response against infection by Cryptosporidium spp. includes all strata of innate and adaptive immunity with differences in their significance. The mucosal immunity, expressed predominantly by the “sentinel” role of epitheliocytes, is fundamental to the resistance against an infection (mainly via activation of the TLR4/NF-κB signalling axis). The vast array of epithelial chemokines and cytokines initiate the local inflammatory processes, attract effector cells and may directly suppress the parasite adhesion. The second line of defence includes IFN-γ-production by the NK cells in combination with their innate cytotoxicity against the parasite and the infected epitheliocytes. The adaptive immunity against the parasite depends predominantly on cytotoxic CD4+ Th1-lymphocytes, which makes IFN-γ central to the acquired response too. CD8+ cells aid to some extent the activity of Th1-cells but their involvement is not decisive. While Cryptosporidium infection elicits the synthesis of specific serum and mucosal antibodies, the humoral immunity is of minor importance. In immunocompromised hosts, infants and malnourished children, the mild and usually self-limiting infection can become life-threatening or take a chronic course. It is the second leading cause of fatal diarrhoea in children and one of the major opportunistic pathogens in the continually expanding group of patients with immunodeficiencies and systemic chronic diseases. Unravelling the mechanisms of resistance against Cryptosporidium infection is fundamental for the successful prevention of the disease. Biomed Rev 2019;30:37-48","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82391696","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}