Beyond clinical changes: Rehabilitation-induced neuroplasticity in MS

2019 ◽  
Vol 25 (10) ◽  
pp. 1348-1362 ◽  
Author(s):  
Luca Prosperini ◽  
Massimiliano Di Filippo
Keyword(s):  
Animal Models ◽  
Neural Plasticity ◽  
Immune Modulation ◽  
Environmental Enrichment ◽  
Small Sample ◽  
Laboratory Research ◽  
Tissue Destruction ◽  
Beneficial Effects ◽  
Network Function

Background: Neural plasticity represents the substrate by which the damaged central nervous system (CNS) re-learns lost behaviors in response to rehabilitation. In persons with multiple sclerosis (MS), rehabilitation can therefore exploit the potential of neural plasticity to restore CNS functions beyond the spontaneous mechanisms of recovery from MS-related damage. Methods: Here, we reviewed the currently available evidence on the occurrence of mechanisms of structural and functional plasticity following rehabilitation, motor, and/or cognitive training. We presented both data gained from basic laboratory research on animal models and data on persons with MS obtained by advanced magnetic resonance imaging (MRI) techniques. Results: Studies on physical and environmental enrichment in experimental MS models showed beneficial effects mediated by both immune modulation and activity-dependent plasticity, lowering tissue destruction and restoring of CNS network function. Translational researches in MS people demonstrated structural and/or functional MRI changes after various interventions, but their heterogeneity and small sample sizes (5–42 patients) raise concerns about the interpretation and generalization of the obtained results. Discussion: We highlighted the limitations of published studies, focusing on the knowledge gaps to be filled in terms of neuropathological correlations between changes detected in animal models and changes detected in vivo by neuroimaging.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals Systematic Review of the Application of Perinatal Derivatives in Animal Models on Cutaneous Wound Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Melanie Pichlsberger ◽  
Urška Dragin Jerman ◽  
Hristina Obradović ◽  
Larisa Tratnjek ◽  
Ana Sofia Macedo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Animal Models ◽  
Cutaneous Wound Healing ◽  
Isolated Cells ◽  
Cutaneous Wound ◽  
Beneficial Effects ◽  
Preclinical Animal Models ◽  
Large Animals ◽  
The Impact

Knowledge of the beneficial effects of perinatal derivatives (PnD) in wound healing goes back to the early 1900s when the human fetal amniotic membrane served as a biological dressing to treat burns and skin ulcerations. Since the twenty-first century, isolated cells from perinatal tissues and their secretomes have gained increasing scientific interest, as they can be obtained non-invasively, have anti-inflammatory, anti-cancer, and anti-fibrotic characteristics, and are immunologically tolerated in vivo. Many studies that apply PnD in pre-clinical cutaneous wound healing models show large variations in the choice of the animal species (e.g., large animals, rodents), the choice of diabetic or non-diabetic animals, the type of injury (full-thickness wounds, burns, radiation-induced wounds, skin flaps), the source and type of PnD (placenta, umbilical cord, fetal membranes, cells, secretomes, tissue extracts), the method of administration (topical application, intradermal/subcutaneous injection, intravenous or intraperitoneal injection, subcutaneous implantation), and the type of delivery systems (e.g., hydrogels, synthetic or natural biomaterials as carriers for transplanted cells, extracts or secretomes). This review provides a comprehensive and integrative overview of the application of PnD in wound healing to assess its efficacy in preclinical animal models. We highlight the advantages and limitations of the most commonly used animal models and evaluate the impact of the type of PnD, the route of administration, and the dose of cells/secretome application in correlation with the wound healing outcome. This review is a collaborative effort from the COST SPRINT Action (CA17116), which broadly aims at approaching consensus for different aspects of PnD research, such as providing inputs for future standards for the preclinical application of PnD in wound healing.

scholarly journals Pharmacological Macrophage Attenuation by Imatinib Reverts Hepatic Steatosis and Inflammation in Obese Mice

2017 ◽  
Author(s):  
Shefaa AlAsfoor ◽  
Theresa V. Rohm ◽  
Angela J. T. Bosch ◽  
Thomas Dervos ◽  
Diego Calabrese ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Immune Modulation ◽  
Diabetic Patients ◽  
Human Monocytes ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Murine Macrophages ◽  
Beneficial Effects

AbstractAimsNon-alcoholic fatty liver disease (NAFLD) has become one of the most common liver diseases worldwide. As macrophages play a key role in NAFLD, therapies targeting macrophages have been postulated. Indeed, strategies depleting macrophages or blocking monocyte recruitment into the liver improve NAFLD, however, are not feasible in clinical practice. Our goal was to assess whether attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, and how this impacts NAFLD.Materials and MethodsMurine macrophages were polarized in vitro to different activation states in the presence or absence of imatinib; mice on high fat diet orally treated with imatinib or vehicle; and human monocytes of diabetic patients and healthy controls treated with or without imatinib for translational application.ResultsImatinib specifically attenuated pro-inflammatory murine macrophages in vitro and in vivo. In livers of obese mice, imatinib caused Kupffer cells to adopt an attenuated phenotype via modulation of the TNFα-pathway. This immune-modulation resulted in markedly improved hepatic steatosis along with beneficial effects on liver function, lipids and systemic inflammation. The immune-dampening effect of imatinib also prevailed in human monocytes, indicating translational applicability.ConclusionsImmune-modulation of myeloid cells as exemplified by imatinib may be a novel therapeutic strategy in patients with NAFLD.

scholarly journals Development and validation of a modularized external fixator for generating standardized fracture healing micromotions in rats

2021 ◽  
Vol 10 (11) ◽  
pp. 714-722
Author(s):  
Weichen Qi ◽  
Xiaoreng Feng ◽  
Teng Zhang ◽  
Hao Wu ◽  
Christian Fang ◽  
...  
Keyword(s):  
Animal Models ◽  
Fracture Healing ◽  
Small Sample Size ◽  
Small Sample ◽  
Experimental Device ◽  
Bench Test ◽  
Large Animal ◽  
Compression Tests ◽  
Large Animal Models

Aims To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. Conclusion Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714–722.

Training the brain: could it improve multiple sclerosis treatment?

2020 ◽  
Vol 31 (7) ◽  
pp. 779-792
Author(s):  
Berenice Anabel Silva ◽  
Esteban Alberto Miglietta ◽  
Carina Cintia Ferrari
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Environmental Enrichment ◽  
Cognitive Stimulation ◽  
Loss Of Function ◽  
Pharmacological Treatments ◽  
Beneficial Effects ◽  
The Central Nervous System ◽  
The Brain ◽  
Multiple Sclerosis Treatment

AbstractMultiple sclerosis (MS) is a neurological disease characterized by neuroinflammation, demyelination and axonal degeneration along with loss of function in the central nervous system. For many years, research in MS has focused on the efficacy of pharmacological treatments. However, during the last years, many publications have been dedicated to the study of the efficacy of non-pharmacological strategies, such as physical exercise and cognitive training. Beneficial effects of the combination of both strategies on cognitive function have been described in both ageing adults and patients with neurodegenerative diseases, such as MS. The analysis of combining both physical and cognitive stimulation can be summarized by the environmental enrichment (EE) experiments, which are more suitable for animal models. EE refers to housing conditions consisting of exercise and cognitive and social stimulation. In this review, we will summarize the available studies that describe the influence of EE in both MS patients and MS animal models.

Probing the ultrastructure of the mitotic and meiotic spindle in eggs: An expeditious approach based on semi-thin (0.25 μm) serial sections

1983 ◽  
Vol 41 ◽  
pp. 552-555
Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder
Keyword(s):  
Small Sample Size ◽  
Small Sample ◽  
Meiotic Spindle ◽  
Serial Sections ◽  
Mitotic Apparatus ◽  
Thin Sections ◽  
Cell Cycles ◽  
Ultrastructural Studies

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).

Curcumin-containing Silver Nanoparticles prevent carbon tetrachlorideinduced hepatotoxicity in mice

2020 ◽  
Vol 23 ◽  
Author(s):  
Hossam Ebaid ◽  
Mohamed Habila ◽  
Iftekhar Hassan ◽  
Jameel Al-Tamimi ◽  
Mohamed S. Omar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Silver Nanoparticles ◽  
Nuclear Dna ◽  
Liquid Paraffin ◽  
Tail Length ◽  
Hepatic Tissue ◽  
Tissue Destruction ◽  
Group 2 ◽  
The Impact

Background: Hepatotoxicity remains an important clinical challenge. Hepatotoxicity observed in response to toxins and hazardous chemicals may be alleviated by delivery of the curcumin in silver nanoparticles (AgNPs-curcumin). In this study, we examined the impact of AgNPs-curcumin in a mouse model of carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Male C57BL/6 mice were divided into three groups (n=8 per group). Mice in group 1 were treated with vehicle control alone, while mice in Group 2 received a single intraperitoneal injection of 1 ml/kg CCl4 in liquid paraffin (1:1 v/v). Mice in group 3 were treated with 2.5 mg/kg AgNPs-curcumin twice per week for three weeks after the CCl4 challenge. Results: Administration of CCL4 resulted in oxidative dysregulation, including significant reductions in reduced glutathione and concomitant elevations in the level of malondialdehyde (MDA). CCL4 challenge also resulted in elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT); these findings were associated with the destruction of hepatic tissues. Treatment with AgNPs-curcumin prevented oxidative imbalance, hepatic dysfunction, and tissue destruction. A comet assay revealed that CCl4 challenge resulted in significant DNA damage as documented by a 70% increase in nuclear DNA tail-length; treatment with AgNPs-curcumin inhibited the CCL4-mediated increase in nuclear DNA tail-length by 34%. Conclusion: Administration of AgNPs-curcumin resulted in significant antioxidant activity in vivo. This agent has the potential to prevent the hepatic tissue destruction and DNA damage that results from direct exposure to CCL4.

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