scholarly journals Role of PPARs in Radiation-Induced Brain Injury

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Sriram Ramanan ◽  
Weiling Zhao ◽  
David R. Riddle ◽  
Mike E. Robbins
Keyword(s):  
Brain Injury ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Whole Brain Irradiation ◽  
Brain Irradiation ◽  
Ppar Agonists ◽  
The Usa ◽  
Radiation Induced

Whole-brain irradiation (WBI) represents the primary mode of treatment for brain metastases; about 200 000 patients receive WBI each year in the USA. Up to 50% of adult and 100% of pediatric brain cancer patients who survive >6 months post-WBI will suffer from a progressive, cognitive impairment. At present, there are no proven long-term treatments or preventive strategies for this significant radiation-induced late effect. Recent studies suggest that the pathogenesis of radiation-induced brain injury involves WBI-mediated increases in oxidative stress and/or inflammatory responses in the brain. Therefore, anti-inflammatory strategies can be employed to modulate radiation-induced brain injury. Peroxisomal proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the steroid/thyroid hormone nuclear receptor superfamily. Although traditionally known to play a role in metabolism, increasing evidence suggests a role for PPARs in regulating the response to inflammation and oxidative injury. PPAR agonists have been shown to cross the blood-brain barrier and confer neuroprotection in animal models of CNS disorders such as stroke, multiple sclerosis and Parkinson's disease. However, the role of PPARs in radiation-induced brain injury is unclear. In this manuscript, we review the current knowledge and the emerging insights about the role of PPARs in modulating radiation-induced brain injury.

scholarly journals Rescue of cognitive function following fractionated brain irradiation in a novel preclinical glioma model

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Xi Feng ◽  
Sharon Liu ◽  
David Chen ◽  
Susanna Rosi ◽  
Nalin Gupta
Keyword(s):  
Tumor Growth ◽  
Cognitive Deficits ◽  
Memory Deficits ◽  
Cognitive Outcomes ◽  
Whole Brain Irradiation ◽  
Clinical Model ◽  
Brain Irradiation ◽  
Reliable Assessment ◽  
Radiation Induced

More than half of long-term brain tumor survivors develop irreversible cognitive decline that severely affect their quality of life. However, there is no pre-clinical model that allows long-term assessment of cognition, and there is no treatment which ameliorates cognitive deficits in patients. Here, we report a novel glioma mouse model that offers manageable tumor growth and reliable assessment of cognitive functions in a post-treatment manner. Using this model, we found that fractionated whole-brain irradiation (fWBI), but not tumor growth, results in memory deficits. Transient inhibition of CSF-1R during fWBI prolongs survival of glioma-bearing mice and fully prevents fWBI-induced memory deficits. This result suggests that CSF-1R inhibition during radiotherapy can be explored as an approach to improve both survival and cognitive outcomes in patients who will receive fWBI. Taken together, the current study provides a proof of concept of a powerful tool to study radiation-induced cognitive deficits in glioma-bearing animals.

scholarly journals The Role of Cytokines and Inflammatory Cells in Perinatal Brain Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Ryan M. McAdams ◽  
Sandra E. Juul
Keyword(s):  
Preterm Birth ◽  
Brain Injury ◽  
Reperfusion Injury ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Perinatal Brain Injury ◽  
The Common ◽  
Hypoxic Ischemic Injury

Perinatal brain injury frequently complicates preterm birth and leads to significant long-term morbidity. Cytokines and inflammatory cells are mediators in the common pathways associated with perinatal brain injury induced by a variety of insults, such as hypoxic-ischemic injury, reperfusion injury, toxin-mediated injury, and infection. This paper examines our current knowledge regarding cytokine-related perinatal brain injury and specifically discusses strategies for attenuating cytokine-mediated brain damage.

scholarly journals Radiation-induced brain injury: current concepts and therapeutic strategies targeting neuroinflammation

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Casmir Turnquist ◽  
Brent T Harris ◽  
Curtis C Harris
Keyword(s):  
Radiation Therapy ◽  
Brain Injury ◽  
Primary Treatment ◽  
Hippocampal Neurogenesis ◽  
Treatment Modalities ◽  
Cancer Therapies ◽  
Radiation Induced ◽  
Cancer Types

Abstract Continued improvements in cancer therapies have increased the number of long-term cancer survivors. Radiation therapy remains one of the primary treatment modalities with about 60% of newly diagnosed cancer patients receiving radiation during the course of their disease. While radiation therapy has dramatically improved patient survival in a number of cancer types, the late effects remain a significant factor affecting the quality of life particularly in pediatric patients. Radiation-induced brain injury can result in cognitive dysfunction, including hippocampal-related learning and memory dysfunction that can escalate to dementia. In this article, we review the current understanding of the mechanisms behind radiation-induced brain injury focusing on the role of neuroinflammation and reduced hippocampal neurogenesis. Approaches to prevent or ameliorate treatment-induced side effects are also discussed along with remaining challenges in the field.

scholarly journals Role of Glucose-Lowering Medications in Erectile Dysfunction

2021 ◽  
Vol 10 (11) ◽  
pp. 2501
Author(s):  
Angelo Cignarelli ◽  
Valentina Annamaria Genchi ◽  
Rossella D’Oria ◽  
Fiorella Giordano ◽  
Irene Caruso ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Current Knowledge ◽  
Smooth Muscle Contractility ◽  
Glucose Lowering ◽  
Glycation End Products ◽  
Altered Metabolism

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

scholarly journals PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Marion Peyrou ◽  
Pierluigi Ramadori ◽  
Lucie Bourgoin ◽  
Michelangelo Foti
Keyword(s):  
Liver Diseases ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Hepatocellular Adenoma ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Ppar Agonists ◽  
Expression And Activity

Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

Lung epithelial NOX/DUOX and respiratory virus infections

2014 ◽  
Vol 128 (6) ◽  
pp. 337-347 ◽  
Author(s):  
Nathalie Grandvaux ◽  
Mélissa Mariani ◽  
Karin Fink
Keyword(s):  
Respiratory Virus ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
In Vivo Studies ◽  
Virus Infections ◽  
Lung Epithelial ◽  
Respiratory Virus Infections

Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.

Sa2015 Traumatic Brain Injury and Intestinal Dysfunction: Investigating a Putative Role of the Brain-Gut Axis in Long-Term Consequences of Injury

2015 ◽  
Vol 148 (4) ◽  
pp. S-384
Author(s):  
Elise L. Ma ◽  
Allen Smith ◽  
Neemesh Desai ◽  
Alan Faden ◽  
Terez Shea-Donohue
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Putative Role ◽  
Long Term Consequences ◽  
The Brain

The Things that Help, the Things that Get in the Way: Working Together to Improve Outcome Following Acquired Brain Injury

2018 ◽  
Vol 19 (3) ◽  
pp. 258-269 ◽  
Author(s):  
Jacinta M. Douglas
Keyword(s):  
Brain Injury ◽  
Acquired Brain Injury ◽  
Life Changes ◽  
Major Life ◽  
The Family ◽  
Working Together ◽  
The Impact ◽  
The Way

Working in neurological rehabilitation brings with it numerous opportunities to gain an understanding of the factors that contribute to shaping meaningful living and wellbeing for those tackling the major life changes encountered following acquired brain injury (ABI). These opportunities come in many forms: challenging and brave clients, wise and worrying families, questioning and inspiring colleagues, empowering and limiting work environments and rigid and advancing policy and legislative contexts.Our personal and collective understanding ofthe things that helpandthe things that get in the wayof effective rehabilitation continuously emerges from the convergence of the experience and knowledge afforded by these opportunities. The aim of this paper is to considerthe things that helpandthe things that get in the wayas they have been identified by people with ABI, their families and those who work with them and have been further evidenced through research targeted towards improving short, medium and long-term outcomes for those living with the consequences of ABI. Thesethingsas discussed in this paper capture the essential role of the self, the importance of rights and access to rehabilitation, the impact of the family and the contribution of social connection.

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