Ovalbumin (OVA), derived from chicken egg, is a frequently used allergen that induces robust, allergic pulmonary inflammation in laboratory rodents. When given by intra-tracheal injection, the acute challenge reproduces many of the key features of clinical asthma, including elevated levels of IgE, airway inflammation, goblet cell hyperplasia, epithelial hypertrophy and persistent airway hyper-responsiveness.
RxCelerate have refined the classical model of allergic asthma by controlling the amount of endotoxin delivered via OVA to the lungs of Brown Norway (BN) rats. This means that the inflammatory response can be directed towards either the TH1 or TH2 pathway, giving us the option to investigate both allergic asthma and/or chronic obstructive pulmonary disease (COPD).
Haemophilia A KO mice (B6;129S-F8tm1Kaz/J) have been genetically engineered to be deficient in clotting factor VIII. Mice are treated with compounds that have the potential to prevent excessive bleeding, and then a tail clip transection is performed. The amount of blood loss at intervals over a 30 minute period is measured using haemoglobin assays.
Previous studies of this nature have transected the tail 2 mm from the tip; a region that will vary in thickness from mouse to mouse. RxCelerate have refined this model by ensuring the tail is always transected at a diameter of 1 mm, irrespective of the distance from the tip.
Nonalcoholic Steatohepatitis (NASH) can be induced in C57 mice via a diet high in fat and fructose. This “fast-food diet” causes mice livers to develop many pathological characteristics of human NASH, including macrovesicular steatosis, acute inflammation, centrilobular fibroplasia and biliary epithelial hyperplasia.
RxCelerate refined and developed a custom high fat and fructose diet, which was easier to handle, more palatable to the animals and produced the pathological hallmarks of NASH within just 12 weeks of starting the diet.
Combining a vascular endothelial growth factor receptor (VEGFR) antagonist, SUGEN 5416 (SU5416), with chronic hypoxia causes pronounced pulmonary arterial hypertension (PAH) in mice and rats. Specifically, the SU5416/hypoxia (SuHx) animals develop increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and angioobliterative lesions in pulmonary arterioles; symptoms which are consistent with human PAH seen in the clinic.
RxCelerate has modified the length of time animals spend in hypoxic conditions, as well as the duration of SU5416 dosing, in order generate a PAH model that most accurately reflects the human condition.
Male Sprague Dawley rats are subjected to up to 2 hours of temporary, middle cerebral artery occlusion (MCAO) by intraluminal silicon coated sutures. Neurobehavioural function and cerebral infarction volume are measured to indicate the severity of a stroke-like condition. As this is a reversible technique, sutures can be removed, leading to reperfusion in the affected area and the return of neurobehavioural function, depending on the length of time of the occlusion.
Mutations in ApoE or the receptor for low-density lipoprotein (Ldl) in humans are associated with hyperlipidemic disorders, leading to an increased susceptibility to atherosclerosis. Mice homozygous for the Apoetm1Unc mutation (ApoE KO mice), and mice homozygous for the Ldlrtm1Her mutation (Ldlr KO mice), show an increase in plasma cholesterol levels and develop atherosclerotic plaques to varying extents under specific dietary conditions. Fibrous vascular plaques appear by 20 weeks of age, and feeding a Western diet can accelerate plaque progression. ApoE KO and Ldl KO mice show many similarities to human atherosclerosis; such as the development of vascular fatty streaks, vascular plaques, fragmentation of the elastic lamina, as well as calcification and wall thinning, making both models suitable for human atherosclerosis research.
Neuropathic pain in humans usually arises as a consequence of a lesion or a disease affecting the somatosensory system. This can be reproduced in rodents using the well-established techniques of either partial ligation or chronic constriction injury (CCI) of the sciatic nerve, which induce hyperalgesia and allodynia-like symptoms.
At RxCelerate, we are proficient in both partial ligation and CCI. We perform blinded weight-bearing tests to measure hyperalgesia, and use von Frey hairs to measure allodynia.
Osteoarthritis (OA) is induced in rats by injecting monosodium iodoacetate (MIA) into the articular space of the hind knee. Hind limb pain is then measured using an incapacitance test meter to determine the level of OA induction. This model is equally suitable for use in mice (endorsed by Simon Westbrook).
RxCelerate refined this model by removing the bias associated with measuring incapacitance by randomising the OA knee and by blinding the operator. In addition, we developed the model to be capable of testing compounds in both a prophylactic and therapeutic paradigm.
Unilateral medial meniscal transection in rats results in rapidly progressive changes in cartilage degeneration, characterised by chondrocyte and proteoglycan loss, fibrillation, osteophyte formation and chondrocyte cloning. These degenerative changes are morphologically similar to those seen in human OA, but occur much more rapidly in rats.
Genetically susceptible DBA/1J mice are immunised with a type II bovine collagen emulsion in complete Freund's adjuvant (CFA). Mice typically develop signs of rheumatoid arthritis (RA) disease 26 to 35 days after the initial injection.
Injecting collagen emulsion in CFA causes ulcers around the injection site if the emulsion leaks from the injection wound. RxCelerate have modified this procedure to make the emulsion thicker, preventing leakage and subsequent ulcer formation.
Standard methods in mice that mimic post-surgical adhesions seen in human patients involve peritoneal abrasions and/or the creation of peritoneal buttons.
All too often, quantifiable, reproducible data using these standard approaches is difficult to achieve. RxCelerate have overcome this by securing the two tissues in close proximity with sutures, so that the exact location, number and tenacity of each adhesion can be measured.