Molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in Guillain-Barré syndrome. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Gangliosides are predominantly cell-surface glycolipids highly expressed in nervous tissue, whilst lipo-oligosaccharides are major components of the Gram-negative bacterium C. jejuni outer membrane. IgG autoantibodies to GM1 ganglioside were found in the sera from patients with Guillain-Barré syndrome. Molecular mimicry was demonstrated between GM1 and lipo-oligosaccharide of C. jejuni isolated from the patients. Disease models by sensitization of rabbits with GM1 and C. jejuni lipo-oligosaccharide were established. Guillain-Barré syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry. Its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in Guillain-Barré syndrome.
Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies.
Spinal cord injury (SCI) is a devastating disorder that has a poor prognosis of recovery. Animal models of SCI are useful to understand the pathophysiology of SCI and the potential use of therapeutic strategies for human SCI. Ex vivo models of central nervous system (CNS) trauma, particularly mechanical trauma, have become important tools to complement in vivo models of injury in order to reproduce the sequelae of human CNS injury. Ex vivo organotypic slice cultures (OSCs) provide a reliable model platform for the study of cell dynamics and therapeutic intervention following SCI. In addition, these ex vivo models support the 3R concept of animal use in SCI research - replacement, reduction and refinement. Ex vivo models cannot be used to monitor functional recovery, nor do they have the intact blood supply of the in vivo model systems. However, the ex vivo models appear to reproduce many of the post traumatic events including acute and secondary injury mechanisms. Several well-established OSC models have been developed over the past few years for experimental spinal injuries ex vivo in order to understand the biological response to injury. In this study, we investigated cell viability in three ex vivo OSC models of SCI: stab injury, transection injury and contusion injury. Injury was inflicted in postnatal day 4 rat spinal cord slices. Stab injury was performed using a needle on transverse slices of spinal cord. Transection injury was performed on longitudinal slices of spinal cord using a double blade technique. Contusion injury was performed on longitudinal slices of spinal cord using an Infinite Horizon impactor device. At days 3 and 10 post-injury, viability was measured using dual staining for propidium iodide and fluorescein diacetate. In all ex vivo SCI models, the slices showed more live cells than dead cells over 10 days in culture, with higher cell viability in control slices compared with injured slices. Although no change in cell viability was observed between time-points in stab- and contusion-injured OSCs, a reduction in cell viability was observed over time in transection-injured OSCs. Taken together, ex vivo SCI models are a useful and reliable research tool that reduces the cost and time involved in carrying out animal studies. The use of OSC models provides a simple way to study the cellular consequences following SCI, and they can also be used to investigate potential therapeutics regimes for the treatment of SCI.
Phyllanthus niruri is a traditional shrub of the genus Phyllanthaceae with long-standing Ayurvedic, Chinese and Malay ethnomedical records. Preliminary studies from cell and animal model have provided valuable scientific evidence for its use.
An invasive aspergillosis model in rabbits was attempted using 3 concentrations of A. fumigatus conidia. Conidia concentrations of 1 x 10(6), 1 x 10(7) and 1 x 10(8) were inoculated intravenously into rabbits. The severity of infection was directly proportional to the inoculum size of the conidia. Aspergillus fumigatus was isolated from livers, kidneys, spleens, hearts and lungs of infected rabbits at a rate of 82%, 75%, 57%, 54% and 32% respectively. Cultures of urine specimens taken by bladder tap were positive for A. fumigatus in 30% of the rabbits tested. Blood cultures using the Bactec Fungal System (Becton Dickinson Corp., USA) failed to isolate A. fumigatus in 20 rabbits with biopsy-proven invasive apergillosis. Active infection with high fungal tissue burden occurred between 2-4 days after infection in rabbits inoculated with 1 x 10(7) conidia.
Neuropathology and neurologic impairment were characterized in a clinically relevant canine model of hypothermic (18°C) circulatory arrest (HCA) and cardiopulmonary bypass (CPB). Adult dogs underwent 2 hours of HCA (n = 39), 1 hour of HCA (n = 20), or standard CPB (n = 22) and survived 2, 8, 24, or 72 hours. Neurologic impairment and neuropathology were much more severe after 2-hour HCA than after 1-hour HCA or CPB; histopathology and neurologic deficit scores were significantly correlated. Apoptosis developed as early as 2 hours after injury and was most severe in the granule cells of the hippocampal dentate gyrus. Necrosis evolved more slowly and was most severe in amygdala and pyramidal neurons in the cornu ammonis hippocampus. Neuronal injury was minimal up to 24 hours after 1-hour HCA, but 1 dog that survived to 72 hours showed substantial necrosis in the hippocampus, suggesting that, with longer survival time, the injury was worse. Although neuronal injury was minimal after CPB, we observed rare apoptotic and necrotic neurons in hippocampi and caudate nuclei. These results have important implications for CPB in humans and may help explain the subtle cognitive changes experienced by patients after CPB.
No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.
The leaf-monkeys, Presbytis cristata and Presbytis melalophos, experimentally infected with subperiodic Brugia malayi, have been used for studies on the pathoimmunology of the infection and the screening of potential filaricides during the last 6-8 years, and considerable information on the pattern of microfilaraemia and adult worm recoveries have been obtained. The prepatent periods in 97 P. cristata and 45 P. melalophos, each infected with about 200 infective larvae, were similar, these being approximately 70 and 68 days respectively. Although all infected animals became microfilaraemic, the peak geometric mean count was much higher in P. cristata than in P. melalophos, this being 182.0 and 65.8 per ml blood respectively. Mean adult worm recovery expressed as the percentage of the infective dose was 4.7% and 2.5%, respectively. Most worms were recovered from the sacral nodes/thoracic duct or inguinal lymph nodes in these animals. In view of the higher worm recovery and the higher peak microfilaraemia attained, it is concluded that P. cristata is a better model for the infection than P. melalophos.
Infective larvae of Brugia malayi subperiodic obtained by dissection of infected Aedes togoi were injected subcutaneously into the scrotal region of Mastomys natalensis. From altogether 58 infected male M. natalensis 81% showed consistently or intermittently detectable microfilaraemia, whereas in 19% of the animals no microfilaraemia could be detected at any stage. The mean prepatent period was 136 days; the microfilarial density varied from 1 to 535 per 20 c. mm blood. In those animlas with consistently detectable and in general higher microfilaraemia an average of 13.1 live adult worms were found, against an average of 6.4 adult worms in animals with intermittent detectable and in general lower microfilaraemia. An average of 1.5 worms was found in animals which at no stage showed detectable microfilaraemia. A correlation between worm burden and prepatent period could be observed in the individual groups. From the total of 520 live adult worms recovered at necropsy, 37% were found in the lungs, 29% in the parenchyma of the testes and 34% in the lymphatic system. 47% of live fertile female worms were found in the lymphatic system, whereas the majority, i.e; 52% of infertile female worms were detected in the lungs. In addition, 380 encapsulated dead worms were found, most of them (98%) in the lymphatic system. 61% of a total of 900 live and dead worms were found in the region of the lymphatic system.
Metabolic syndrome is a cluster including hyperglycaemia, obesity, hypertension, and hypertriglyceridaemia as a result of biochemical and physiological alterations and can increase the risk of cardiovascular disease and diabetes. Fundamental research on this disease requires validated animal models. One potential animal model that is rapidly gaining in popularity is zebrafish (Danio rerio). The use of zebrafish as an animal model conveys several advantages, including high human genetic homology, transparent embryos and larvae that allow easier visualization. This review discusses how zebrafish models contribute to the development of metabolic syndrome studies. Different diseases in the cluster of metabolic syndrome, such as hyperglycaemia, obesity, diabetes, and hypertriglyceridaemia, have been successfully studied using zebrafish; and the model is promising for hypertension and cardiovascular metabolic-related diseases due to its genetic similarity to mammals. Genetic mutation, chemical induction, and dietary alteration are among the tools used to improve zebrafish models. This field is expanding, and thus, more effective and efficient techniques are currently developed to fulfil the increasing demand for thorough investigations.
Metabolic syndrome (MetS) consists of several medical conditions that collectively predict the risk for cardiovascular disease better than the sum of individual conditions. The risk of developing MetS in human depends on synergy of both genetic and environmental factors. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of appropriate experimental animal models mimicking the disease state in humans is crucial in order to solve the difficulties in evaluating the pathophysiology of MetS in human. This review aims to summarize the underlying mechanisms involved in the pathophysiology of dietary, genetic, and pharmacological models of MetS. Furthermore, we will discuss the usefulness, suitability, pros and cons of these animal models. Even though numerous animal models of MetS have been established, further investigations on the invention of new animal model and clarification of plausible mechanisms are still necessary to confer a better understanding to researchers on the selection of animal models for their studies.
Previous studies have proven the existence of a complex association
between progressive kidney damage and hypercholesterolemia. Most studies focused on
the impact of chronic high blood cholesterol levels on the kidney. Information on the
early effect of hypercholesterolemia on the kidney is still lacking. The aim of this study
was therefore to determine early effect of high cholesterol diet on the kidney in an
animal model. (Copied from article).
Although there is a growing insight into the causes and mechanisms of
kidney diseases, preventive and therapeutic measures are still few. The aim of this study
was therefore to determine the renoprotective effect of tualang honey against high
cholesterol diet induced acute kidney disease in an animal model. (Copied from article).
Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality that usually results in the development of multiple organ dysfunction. The complex pathophysiology of ALI seems to provide a wide range of targets that offer numerous therapeutic options. However, despite extensive studies of ALI pathophysiology and treatment, no effective pharmacotherapy is available. Increasing evidence from both preclinical and clinical studies supports the preventive and therapeutic effects of mesenchymal stem cells (MSCs) for treating ALI. As cell-based therapy poses the risk of occlusion in microvasculature or unregulated growth, MSC-derived extracellular vesicles (MSC-EVs) have been extensively studied as a new therapeutic strategy for non-cell based therapy. It is widely accepted that the therapeutic properties of MSCs are derived from soluble factors with paracrine or endocrine effects, and EVs are among the most important paracrine or endocrine vehicles that can deliver various soluble factors with a similar phenotype as the parent cell. Therapeutic effects of MSCs have been reported for various delivery approaches, diverse doses, multiple origins, and different times of administration, and MSC-EVs treatment may include but is not limited to these choices. The mechanisms by which MSCs and MSC-EVs may contribute to ALI treatment remain elusive and need further exploration. This review provides an overview of preclinical studies that support the application of MSC-EVs for treating ALI, and it discusses emerging opportunities and their associated challenges.
Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are a prognostic genetic model of absence epilepsy. This model displays the electro-clinical, behavioural, and pharmacological features of absence seizures. Although GAERS share typical characteristics, including spike-and-wave discharges (SWDs) in the electroencephalography (EEG), age-dependent studies with these animals have not yet been reported. The aim of the present study is to perform a systematic comparison contrasting the SWDs of young and older GAERS, in terms of the number, duration, frequency, and waveform morphology of the discharges, as well as the pre-SWD EEG characteristics, using identical measurement and analysis techniques. The number, cumulative total duration and mean duration of SWDs were significantly higher in young GAERS (4 to 6 months) compared to older GAERS (12 to 14 months). Furthermore, the SWD spectra and average SWD waveforms indicated that a single cycle of the SWD contains more energy in faster components, such as increased spikes and higher power, in the SWDs of the young GAERS. Additionally, older GAERS showed weak amplitude spikes in SWDs and higher power pre-SWDs. These clear morphological differences in the EEGs of young and older GAERS rats should be further examined in future studies that explore new dimensions of genetic absence epilepsy.
Hypnale hypnale (hump-nosed pit viper) is a medically important venomous snake in Sri Lanka and Southwestern India. Bite of this snake may result in hemostatic dysfunction, acute kidney injury and death. Clinical studies indicated that the locally available polyvalent antivenoms produced in India are not effective against hump-nosed pit viper envenoming. Hence, there is an urgent need to search for effective antivenom. In this paper, we examined the ability of Calloselasma rhodostoma (Malayan pit viper) monovalent antivenom and the Hemato polyvalent antivenom (both produced by Thai Red Cross Society, TRCS) to neutralize the lethality and toxic effects of H. hypnale venom, as C. rhodostoma is considered a sister taxon of H. hypnale. In vitro neutralization studies showed that the Hemato polyvalent antivenom effectively neutralized the lethality of H. hypnale venom (1.52mgvenom/mL antivenom) as well as the hemorrhagic, procoagulant and necrotic activities of the venom. The monovalent C. rhodostoma antivenom could also neutralize the lethality and toxic activities of the venom, but the potency was lower. The Hemato polyvalent antivenom also effectively protected mice from the lethal and local effects of H. hypnale venom in an in vivo rodent model of envenoming. Furthermore, the polyvalent antivenom could also effectively neutralize the venom of Daboia russelii (2.50mgvenom/mL antivenom), another common cause of snake bites in Sri Lanka and South India. These findings suggested that the Hemato polyvalent antivenom may be beneficial in the antivenom treatment of H. hypnale envenoming.
The antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p