Leprosy patients: neurotrophic factors and axonal markers in skin lesions

Abstract

The main principles of leprosy control consist of early detection of new cases, proper treatment by multidrug therapy (MDT), prevention of disabilities and rehabilitation 1 . In spite of worldwide efforts, endemic countries still have leprosy control as an unreached goal. The prevention and recovery of peripheral neuropathy are among the hardest challenges of leprosy. In Brazil, approximately 5.9% of new cases of leprosy present grade II of disability at the moment of first diagnosis 1 . Unfortunately, the established neural impairment tends to persist as lifelong sequelae in these patients 2 .Mycobacterium leprae (M. leprae) has tropism for the peripheral nervous system, where it infects Schwann cells and eventually endothelium Key words: peripheral nerves, leprosy. RESUMONeurotrofinas são fatores de crescimento com papel fundamental na fisiopatologia neural. Esses mediadores modulam funcionalmente fibras nociceptivas. Mudanças em sua expressão têm sido relacionadas à perda precoce da nocicepção na hanseníase. Este estudo investigou a expressão de NGF, BDNF e NT3 em nervos dérmicos de pacientes hansenianos. A caracterização de fibras nervosas não mielinizadas foi feita por p75 NTR e marcadores axonais NF-L e PGP 9.5. Os parâmetros clínicos de dano neural foram avaliados por monofilamentos Semmes-Wenstein. Nossos achados demonstram diminuição de NGF nos pacientes dimorfos em comparação aos controles. Resultados similares foram observados para PGP 9.5 (dimorfos: p<0,001; virchowianos: p<0,05) e NF-L (virchowianos: p<0.05), sugerindo degeneração avançada das terminações nervosas na hanseníase multibacilar. Foi observada correlação positiva entre p75 NTR e PGP 9.5, indicando associação entre células de Schwann e axônios em fibras nervosas não mielinizadas. Os resultados indicam que o desequilíbrio na expressão das neurotrofinas pode participar do dano neural periférico.Palavras-Chave: nervos periféricos, hanseníase.

An inducible Cre mouse line to sparsely target nervous system cells, including Remak Schwann cells

“…We first asked if RSCs show Cre activity. The ECSF;Ai14 double heterozygote mice from ECSF X Ai14 cross were injected with either tamoxifen or vehicle control (sunflower oil), and their sciatic nerves were immunostained for p75 neurotrophin receptor (p75NTR), which marks Remak bundles [14]. Robust expression of TdTomato was observed in the nerves from tamoxifen-treated mice, but not in those from vehicle-treated mice, evidencing a stringent inducibility of the Cre activity ( Fig.…”

An inducible Cre mouse line to sparsely target nervous system cells, including Remak Schwann cells

“…We first asked if RSCs show Cre activity. The ECSF;Ai14 double heterozygote mice from ECSF X Ai14 cross were injected with either tamoxifen or vehicle control (sunflower oil), and their sciatic nerves were immunostained for p75 neurotrophin receptor (p75NTR), which has been used to mark Remak bundles 14 . A robust expression of TdTomato was present in the nerves from tamoxifen-treated mice but not in those from vehicle-treated mice, evidencing a stringent inducibility of the Cre activity (Fig.…”

Demyelination in Leprosy

“…The test is performed using five different single filaments, i.e., 200 mg, 2 g, 4 g, 10 g, and 300 g. Each site is then assessed by the perceived filament, which is the heaviest monofilament obtained and the highest value with a total value of 15 for the ulnar, median, and radial (four filaments) nerves and a total value of 12 for the foot (three filaments). The normal threshold value is 200 mg for the hand and 2 g for the foot (other than the heel) [10,11]. This test is considered positive if the MFT value is 3 for each nerve.…”

“…Until now leprosy treatment is only for eradication of bacteria, but it cannot prevent or cure peripheral nerve damage and its components, so early detection to determine the presence of bacteria in Schwann cells is important [6,7]. Several studies in early detection of nerve damage by invasion of M. leprae have been conducted, namely, using ultrasound to detect peripheral nerve damage [8], vasomotor reflex and sympathetic skin responses [9], electrophysiology of the peripheral nerves involved [10], and examining axonal markers on skin lesions [11]. There is Ridley-Jopling classification of leprosy based on clinical, bacteriological, histological, and immunological symptoms.…”