ABSTRACT
BACKGROUND: Nerve transfers are a powerful tool in extremity reconstruction, but the neurophysiological effects have not been adequately investigated. As 81 % of nerve injuries and most nerve transfers occur in the upper extremity with its own neurophysiological properties, the standard rat hindlimb model may not be optimal in this paradigm. Here we present an experimental rat forelimb model to investigate nerve transfers. METHODS: In ten male Sprague-Dawley rats, the ulnar nerve was transferred to the motor branch of long head of the biceps. Sham surgery was performed in five animals (exposure/closure). After 12 weeks of regeneration, muscle force and Bertelli test were performed and evaluated. RESULTS: The nerve transfer successfully reinnervated the long head of the biceps in all animals, as indicated by muscle force and behavioral outcome. No aberrant reinnervation occurred from the original motor source. Muscle force was 2,68 N ± 0.35 for the nerve transfer group and 2,85 N ± 0.39 for the sham group, which was not statically different (p = 0.436). The procedure led to minor functional deficits due to the loss of ulnar nerve function; this, however, could not be quantified with any of the presented measures. CONCLUSION: The above-described rat model demonstrated a constant anatomy, suitable for nerve transfers that are accessible to standard neuromuscular analyses and behavioral testing. This model allows the study of both neurophysiologic properties and cognitive motor function after nerve transfers in the upper extremity.
ABSTRACT
BACKGROUND: The major house dust mite allergen Der p 2 is a structural and functional homologue of MD-2 within the TLR4-CD14-MD-2 complex. An asthma mouse model in TLR4-deficient mice recently suggested that the allergic immune response against Der p 2 is solely dependent on TLR4 signaling. We investigated whether similar mechanisms are important for Der p 2 sensitization via the skin. METHODS: In an epicutaneous sensitization model, the response to recombinant Der p 2 in combination with or without lipopolysaccharide (LPS) was compared between C57BL/6 WT and TLR4-deficient mice. We further analyzed possible adjuvant function of exogenous cysteine proteases. RESULTS: Sensitization with rDer p 2 induced similar levels of allergen-specific IgG1 and IgE antibodies in both mouse strains. LPS increased the systemic (antibody levels, cytokine release by restimulated splenocytes) and local (infiltration of immune cells into the skin) Th2 immune responses, which against our expectations were stronger in the absence of functional TLR4 expression. Barrier disruption by papain, a protease with structural homology to Der p 1, did not enhance the sensitization capacity of rDer p 2. However, the presence of LPS increased the stability of rDer p 2 against the protease. CONCLUSION: Our data suggest that rDer p 2 alone can cause a strong TH 2-biased response via the skin being enhanced in the presence of LPS. This response is not reliant on functional TLR4, but vice versa TLR4 expression rather protects against epicutaneous sensitization to house dust mite allergen Der p 2.
