Experimental nerve transfer model in the neonatal rat

Clinically,peripheral nerve reconstructions in neonates are most frequently applied in brachial plexus birth injuries.Most surgical concepts,however,have investigated nerve reconstructions in adult animal models.The immature neuromuscular system reacts differently to the effects of nerve lesion and surgery and is poorly investigated due to the lack of reliable experimental models.Here,we describe an experimental forelimb model in the neonatal rat,to study these effects on both the peripheral and central nervous systems.Within 24 hours after birth,three groups were prepared:In the nerve transfer group,a lesion of the musculocutaneous nerve was reconstructed by selectively transferring the ulnar nerve.In the negative control group,the musculocutaneous nerve was divided and not reconstructed and in the positive control group,a sham surgery was performed.The animal's ability to adapt to nerve lesions and progressive improvement over time were depict by the Bertelli test,which observes the development of grooming.Twelve weeks postoperatively,animals were fully matured and the nerve transfer successfully reinnervated their target muscles,which was indicated by muscle force,muscle weight,and cross sectional area evaluation.On the contrary,no spontaneous regeneration was found in the negative control group.In the positive control group,reference values were established.Retrograde labeling indicated that the motoneuron pool of the ulnar nerve was reduced following nerve transfer.Due to this post-axotomy motoneuron death,a diminished amount of motoneurons reinnervated the biceps muscle in the nerve transfer group,when compared to the native motoneuron pool of the musculocutaneous nerve.These findings indicate that the immature neuromuscular system behaves profoundly different than similar lesions in adult rats and explains reduced muscle force.Ultimately,pathophysiologic adaptations are inevitable.The maturing neuromuscular system,however,utilizes neonatal capacity of regeneration and seizes a variety of compensation mechanism to restore a functional extremity.The above described neonatal rat model demonstrates a constant anatomy,suitable for nerve transfers and allows all standard neuromuscular analyses.Hence,detailed investigations on the pathophysiological changes and subsequent effects of trauma on the various levels within the neuromuscular system as well as neural reorganization of the neonatal rat may be elucidated.This study was approved by the Ethics Committee of the Medical University of Vienna and the Austrian Ministry for Research and Science(BMWF-66.009/0187-WF/V/3 b/2015)on March 20,2015.

High yield reproducible rat model recapitulating human Barrett's carcinogenesis

AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma(EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10(n = 6),17(n = 8),24(n = 9),31(n = 6),38(n = 6),and 40(n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation wascompleted to determine respective rates of carcinogenic development. Quantitative reverse transcriptionpolymerase chain reaction was performed to determine gene expression levels of MUC2,CK19,and CK20,and results were compared to determine significant differences throughout disease progression stages.RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak,gastrointestinal hemorrhage,stomach ulcer perforation,respiratory infection secondary to aspiration,and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery,100% of animals presented with esophagitis. Barrett's esophagus(BE) was first observed at 10 wk,and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk,and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition,two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine,respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden,which may facilitate broader adoption to study EAC development,progression,and therapeutics.

Establishment of rat experiment model of chronic allograft nephropathy

Objective To summarize experience of establishing stable rat model ot chronic allograft nephropathy. Methods We used Fisher rats as donors and Lewis rats as recipients. After left kidney of donor perfused in situ under hypothermic condition,left renal vein,abdominal aorta and bladder flap of donor was anastomosed with