Role of the GABAA receptors in the long-term cognitive impairments caused by neonatal sevoflurane exposure

2019 ◽  
Vol 30 (8) ◽  
pp. 869-879 ◽  
Author(s):  
Tao Li ◽  
Zeyi Huang ◽  
Xianwen Wang ◽  
Ju Zou ◽  
Sijie Tan
Keyword(s):  
Structural Changes ◽  
Cognitive Impairments ◽  
Elevated Serum ◽  
Developmental Abnormalities ◽  
Inhalational Anesthetic ◽  
Excitatory Gaba ◽  
Hpa Axis Activity ◽  
The Brain

Abstract Sevoflurane is a widely used inhalational anesthetic in pediatric surgeries, which is considered reasonably safe and reversible upon withdrawal. However, recent preclinical studies suggested that peri-neonatal sevoflurane exposure may cause developmental abnormalities in the brain. The present review aimed to present and discuss the accumulating experimental data regarding the undesirable effects of sevoflurane on brain development as revealed by the laboratory studies. First, we summarized the long-lasting side effects of neonatal sevoflurane exposure on cognitive functions. Subsequently, we presented the structural changes, namely, neuroapoptosis, neurogenesis and synaptogenesis, following sevoflurane exposure in the immature brain. Finally, we also discussed the potential mechanisms underlying subsequent cognitive impairments later in life, which are induced by neonatal sevoflurane exposure and pointed out potential strategies for mitigating sevoflurane-induced long-term cognitive impairments. The type A gamma-amino butyric acid (GABAA) receptor, the main targets of sevoflurane, is excitatory rather than inhibitory in the immature neurons. The excitatory effects of the GABAA receptors have been linked to increased neuroapoptosis, elevated serum corticosterone levels and epigenetic modifications following neonatal sevoflurane exposure in rodents, which might contribute to sevoflurane-induced long-term cognitive abnormalities. We proposed that the excitatory GABAA receptor-mediated HPA axis activity might be a novel mechanism underlying sevoflurane-induced long-term cognitive impairments. More studies are needed to investigate the effectiveness and mechanisms by targeting the excitatory GABAA receptor as a prevention strategy to alleviate cognitive deficits induced by neonatal sevoflurane exposure in future.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani
Keyword(s):  
Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Culture Conditions ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Inflammatory Molecules ◽  
The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

scholarly journals Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain

2018 ◽  
Vol 10 (471) ◽  
pp. eaan0237 ◽  
Author(s):  
Diego F. Niño ◽  
Qinjie Zhou ◽  
Yukihiro Yamaguchi ◽  
Laura Y. Martin ◽  
Sanxia Wang ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Microglial Activation ◽  
Gastrointestinal Disease ◽  
Cognitive Impairments ◽  
High Mobility ◽  
Neurological Dysfunction ◽  
Mucosal Inflammation ◽  
Signaling Axis ◽  
The Brain

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.

Leptin Functioning in Eating Disorders

CNS Spectrums ◽  
2004 ◽  
Vol 9 (7) ◽  
pp. 523-529 ◽  
Author(s):  
Palmiero Monteleone ◽  
Antonio DiLieto ◽  
Eloisa Castaldo ◽  
Mario Maj
Keyword(s):  
Physical Activity ◽  
Eating Disorders ◽  
Body Weight ◽  
Eating Behaviors ◽  
Clinical Manifestations ◽  
Immune Functions ◽  
Abnormal Eating ◽  
The Brain

AbstractLeptin is an adipocyte-derived hormone, which is involved predominantly in the long-term regulation of body weight and energy balance by acting as a hunger suppressant signal to the brain. Leptin is also involved in the modulation of reproduction, immune function, physical activity, and some endogenous endocrine axes. Since anorexia nervosa (AN) and bulimia nervosa (BN) are characterized by abnormal eating behaviors, dysregulation of endogenous endocrine axes, alterations of reproductive and immune functions, and increased physical activity, extensive research has been carried out in the last decade in order to ascertain a role of this hormone in the pathophysiology of these syndromes. In this article, we review the available data on leptin physiology in patients with eating disorders. These data support the idea that leptin is not directly involved in the etiology of AN or BN. However, malnutrition-induced alterations in its physiology may contribute to the genesis and/or the maintenance of some clinical manifestations of AN and BN and may have an impact on the prognosis of AN.

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.

Persistent Pulmonary Hypertension of the Newborn: Role of Nitric Oxide

1995 ◽  
Vol 10 (6) ◽  
pp. 270-282
Author(s):  
Stella Kourembanas
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Structural Changes ◽  
Critical Role ◽  
Persistent Pulmonary Hypertension ◽  
Cell Contractility ◽  
Vasoactive Mediators ◽  
Nitric Oxide Therapy

Persistent pulmonary hypertension of the newborn (PPHN) is a common cause of respiratory failure in the full-term neonate. Molecular and cellular studies in vascular biology have revealed that endothelial-derived mediators play a critical role in the pathogenesis and treatment of PPHN. Endothelial-derived vasoconstrictors, like endothelin, may increase smooth muscle cell contractility and growth, leading to the physiologic and structural changes observed in the pulmonary arterioles of infants with this disease. On the other hand, decreased production of the endothelial-derived relaxing factor, nitric oxide, may exacerbate pulmonary vasoreactivity and lead to more severe pulmonary hypertension. Exogenous (inhaled) nitric oxide therapy reduces pulmonary vascular resistance and improves oxygenation. The safety and efficacy of this therapy in reducing the need for extracorporeal membrane oxygenation and decreasing long-term morbidity is being tested in several trials nationally and abroad. Understanding the basic mechanisms that regulate the gene expression and production of these vasoactive mediators will lead to improved preventive and therapeutic strategies for PPHN.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals Optogenetics and photopharmacology in pain research and therapeutics

STEMedicine ◽  
2020 ◽  
Vol 1 (3) ◽  
pp. e43 ◽  
Author(s):  
Federico Iseppon ◽  
Manuel Arcangeletti
Keyword(s):  
Chronic Pain ◽  
Pain Treatment ◽  
Molecular Switches ◽  
Genetic Profiling ◽  
Pain Research ◽  
Recent Advances ◽  
Cellular Components ◽  
The Brain

Pain afflicts billions of people worldwide, who suffer especially from long-term chronic pain. This gruelling condition affects the nervous system at all levels: from the brain to the spinal cord, the Dorsal Root Ganglia (DRG) and the peripheral fibres innervating the skin. The nature of the different molecular and cellular components of the somatosensory modalities, as well as the complexity of the peripheral and central circuitry are yet poorly understood. Light-based techniques such as optogenetics, in concert with the recent advances in single-cell genetic profiling, can help to elucidate the role of diverse neuronal sub-populations in the encoding of different sensory and painful stimuli by switching these neurons on and off via optically active proteins, namely opsins.  Recently, photopharmacology has emerged from the efforts made to advance optogenetics. The introduction of azo-benzene-based light-sensitive molecular switches has been applied to a wide variety of molecular targets, from ion channels and receptors to transporters, enzymes and many more, some of which are paramount for pain research and therapy. In this Review, we summarise the recent advances in the fields of optogenetics and photopharmacology and we discuss the use of light-based techniques for the study of acute and chronic pain physiology, as well as their potential for future therapeutic use to improve pain treatment.

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

scholarly journals Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

2006 ◽  
Vol 361 (1471) ◽  
pp. 1159-1185 ◽  
Author(s):  
B Beck
Keyword(s):  
Neuropeptide Y ◽  
Diet Composition ◽  
High Energy ◽  
Glucose Sensing ◽  
Feeding Regulation ◽  
Treatment Of Obesity ◽  
The Brain ◽  
Diet Type

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db / db mouse, or at the peptide level, as in ob / ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka–Long–Evans–Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.

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