02979nas a2200289 4500000000100000008004100001260001200042653002500054653002500079653001500104653001200119653003000131653001700161100001100178700001300189700001500202700001200217700001500229700001300244700001200257245011200269856008000381300001100461490000600472520219700478022001402675 2022 d c01/202210aDasypus novemcinctus10aMycobacterium leprae10aArmadillos10aleprosy10aNerve function impairment10aneuropathies1 aPena M1 aLahiri R1 aEbenezer G1 aWheat S1 aFigarola J1 aTruman R1 aAdams L00aThe Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259846/pdf/fmed-09-879097.pdf a8790970 v93 a

infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for -induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves. In this study, state-of-the-art technology was used to compare nerve function between uninfected and -infected armadillos. Motor nerve conduction velocity (MNCV) and compound muscle action potential (cMAP), which measure changes in the rate of impulse conduction velocity and amplitude, revealed a progression of impairment that was directly correlated with the duration of infection and enabled development of an objective nerve impairment scoring system. Ultrasonography accompanied by color Doppler imaging detected enlargement of the -infected nerves and increased vascularity, possibly due to inflammation. Assessment of epidermal nerve fiber density (ENFD), which shows a length-dependent innervation in armadillos that is similar to humans, identified small fiber degeneration early after infection. Staining for neuromuscular junction (NMJ) integrity, which is an indicator of signal transduction efficiency into skeletal muscle, discerned a markedly lower number and structural integrity of NMJ in -infected armadillo footpads. These tools for assessing nerve injury were used to monitor the effects of intervention therapy. Two potential neuro-protective drugs, ethoxyquin (EQ) and 4-aminopyridine (4-AP), were tested for their ability to ameliorate peripheral nerve injury in -infected armadillos. 4-AP treatment improved MNCV, cMAP, and EFND compared to untreated animals, while EQ had less effect. These results support the armadillo as a model for -induced peripheral nerve injury that can provide insights toward the understanding of NFI progression and contribute to the preclinical investigation of the safety and efficacy of neuro-preventive and neuro-therapeutic interventions for leprosy.

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