scholarly journals Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Mikhail Stepanichev ◽  
Nikolay N. Dygalo ◽  
Grigory Grigoryan ◽  
Galina T. Shishkina ◽  
Natalia Gulyaeva
Keyword(s):  
Neurotrophic Factors ◽  
Brain Plasticity ◽  
Experimental Models ◽  
Stress Factors ◽  
Normal Brain ◽  
Rodent Models ◽  
Regulatory Systems ◽  
Treatment Of Depression ◽  
Therapeutic Measures ◽  
Indispensable Tool

Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive) during early life (including prenatal period) or adulthood, giving emphasis to the data on the changes of neurotrophic factors and neuroinflammatory indices in the brain. These parameters are closely related to behavioral depression-like symptoms and impairments of neuronal plasticity and are both gender- and genotype-dependent. Stress-related changes in expression of neurotrophins and cytokines in rodent brain are region-specific. Some contradictory data reported by different groups may be a consequence of differences of stress paradigms or their realization in different laboratories. Like all experimental models, stress-induced depression-like conditions are experimental simplification of clinical depression states; however, they are suitable for understanding the involvement of neurotrophic factors and cytokines in the pathogenesis of the disease—a goal unachievable in the clinical reality. These major regulatory systems may be important targets for therapeutic measures as well as for development of drugs for treatment of depression states.

scholarly journals Multiple Disruptions of Glial-Neuronal Networks in Epileptogenesis That Follows Prolonged Febrile Seizures

2021 ◽  
Vol 12 ◽  
Author(s):  
Gary P. Brennan ◽  
Megan M. Garcia-Curran ◽  
Katelin P. Patterson ◽  
Renhao Luo ◽  
Tallie Z. Baram
Keyword(s):  
Neuronal Networks ◽  
Day Treatment ◽  
High Mobility ◽  
Febrile Seizures ◽  
Experimental Models ◽  
Normal Brain ◽  
Molecular Signaling ◽  
Rat Pups ◽  
Anti Inflammatory

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE).Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone.Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE–experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes.Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.

A Review on Preclinical Models of Ischemic Stroke: Insights Into the Pathomechanisms and New Treatment Strategies

2021 ◽  
Vol 19 ◽  
Author(s):  
Aditya A Singh ◽  
Akash Kharwar ◽  
Manoj P. Dandekar
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Neurotrophic Factors ◽  
Treatment Strategies ◽  
Experimental Models ◽  
Cerebral Stroke ◽  
Post Stroke ◽  
Stroke Models

Background: Stroke is a serious neurovascular problem and the leading cause of disability and death worldwide. The disrupted demand to supply ratio of blood and glucose during cerebral ischemia develops hypoxic shock, and subsequently necrotic neuronal death in the affected regions. Multiple causal factors like age, sex, race, genetics, diet, and lifestyle play an important role in the occurrence as well as progression of post-stroke deleterious events. These biological and environmental factors may be contributed to vasculature variable architecture and abnormal neuronal activity. Since recombinant tissue plasminogen activator is the only clinically effective clot bursting drug, there is a huge unmet medical need for newer therapies for the treatment of stroke. Innumerous therapeutic interventions have shown promise in the experimental models of stroke but failed to translate it into clinical counterparts. Methods: Original publications regarding pathophysiology, preclinical experimental models, new targets and therapies targeting ischemic stroke have been reviewed since the 1970s. Results: We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Results : We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Conclusion: There are still many inter-linked pathophysiological alterations with regards to stroke, animal models need not necessarily mimic the same conditions of stroke pathology and newer targets and therapies are the need of the hour in stroke research.

Molecular and Cellular Pathogenesis of Depression and Mechanisms for Treatment Response

2013 ◽  
pp. 425-437
Author(s):  
Ronald S. Duman
Keyword(s):  
Amino Acid ◽  
Neurotrophic Factors ◽  
Limbic Structures ◽  
Brain Circuits ◽  
Antidepressant Agent ◽  
Treatment Of Depression ◽  
Cellular Pathogenesis ◽  
Gaba Transmission ◽  
Stress Models ◽  
New Generation

Early theories of depression were centered on the monoamines, but more recent work has focused on the amino acid neurotransmitters, glutamate and GABA. Imbalances of glutamate and GABA transmission in key cortical and limbic structures are thought to contribute to disruption of brain circuits that control emotion and mood. These imbalances, together with stress activated pathways that regulate neurotrophic factors and inflammatory cytokines could contribute to atrophy and loss of neurons observed in depressed patients and rodent stress models. The significance of synaptic connections in depression is highlighted by new studies demonstrating that a rapid acting, highly efficacious antidepressant agent increases synaptogenesis, paving the way for a new generation of medications for the treatment of depression.

scholarly journals A review of the efficacy of dietary polyphenols in experimental models of inflammatory bowel diseases

2015 ◽  
Vol 6 (6) ◽  
pp. 1773-1786 ◽  
Author(s):  
Derek A. Martin ◽  
Bradley W. Bolling
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Experimental Models ◽  
Rodent Models ◽  
Dietary Polyphenols ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Higher Doses

The use of polyphenols in rodent models of inflammatory bowel diseases is reviewed. Many polyphenols inhibit colitis through multiple mechanisms, however higher doses of some treatments may exacerbate inflammation.

scholarly journals Echocardiographic assessment of right ventricular function in experimental pulmonary hypertension

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401984198 ◽  
Author(s):  
Zhongkai Zhu ◽  
Dureti Godana ◽  
Ailing Li ◽  
Bianca Rodriguez ◽  
Chenxin Gu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Cost Effective ◽  
Experimental Models ◽  
Clinical Diagnostics ◽  
Rodent Models ◽  
Ejection Time ◽  
Non Invasive ◽  
Cost Effective Method ◽  
Rv Function

Echocardiography, a non-invasive and cost-effective method for monitoring cardiac function, is commonly used for evaluation and pre-clinical diagnostics of pulmonary hypertension (PH). Previous echocardiographic studies in experimental models of PH are fragmentary in terms of the evaluation of right ventricle (RV) function. In this study, three rodent models of PH: a mouse model of hypoxia-induced PH, a rat model of hypoxia+Sugen induced PH and a rat model of monocrotaline-induced PH, were employed to measure RV fractional area change (RVFAC), RV free wall thickness (RVFWT), pulmonary acceleration time (PAT), pulmonary ejection time (PET), and tricuspid annular plane systolic excursion (TAPSE). We found that, in these models, RVFWT significantly increased, but RVFAC, PAT, or PAT/PET ratios and TAPSE values significantly decreased. Accurate and complete TAPSE patterns were demonstrated in the three rodent models of PH. The RV echocardiography data matched the corresponding invasive hemodynamic and heart histologic data in each model. This serves as a reference study for real-time and non-invasive evaluation of RV function in rodent models of PH using echocardiography.

scholarly journals Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Amaury Vanvinckenroye ◽  
Gilles Vandewalle ◽  
Christophe Phillips ◽  
Sarah L. Chellappa
Keyword(s):  
In Silico ◽  
Brain Function ◽  
Computational Models ◽  
Temporal Dynamics ◽  
Brain Plasticity ◽  
Effective Connectivity ◽  
Normal Brain ◽  
Cortical Function ◽  
Eyes Open

Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states.

scholarly journals The Potential Application of Endophytes in Management of Stress from Drought and Salinity in Crop Plants

2021 ◽  
Vol 9 (8) ◽  
pp. 1729
Author(s):  
Hariom Verma ◽  
Dharmendra Kumar ◽  
Vinod Kumar ◽  
Madhuree Kumari ◽  
Sandeep Kumar Singh ◽  
...  
Keyword(s):  
Abiotic Stresses ◽  
Potential Application ◽  
Crop Yields ◽  
Climatic Conditions ◽  
Crop Plants ◽  
Stress Factors ◽  
Ph Variation ◽  
Regulatory Systems ◽  
Protection Systems ◽  
Potential Applications

Endophytic microorganisms present inside the host plant play an essential role in host fitness, nutrient supply and stress tolerance. Endophytes are often used in sustainable agriculture as biofertilizers, biopesticides and as inoculants to mitigate abiotic stresses including salinity, drought, cold and pH variation in the soil. In changing climatic conditions, abiotic stresses create global challenges to achieve optimum crop yields in agricultural production. Plants experience stress conditions that involve endogenous boosting of their immune system or the overexpression of their defensive redox regulatory systems with increased reactive oxygen species (ROS). However, rising stress factors overwhelm the natural redox protection systems of plants, which leads to massive internal oxidative damage and death. Endophytes are an integral internal partner of hosts and have been shown to mitigate abiotic stresses via modulating local or systemic mechanisms and producing antioxidants to counteract ROS in plants. Advancements in omics and other technologies have been made, but potential application of endophytes remains largely unrealized. In this review article, we will discuss the diversity, population and interaction of endophytes with crop plants as well as potential applications in abiotic stress management.

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