Impaired reinnervation in HIV infection following experimental denervation

Hahn, Katrin; Triolo, A; Hauer, Peter; McArthur, Justin C.; Polydefkis, Michael

doi:10.1212/01.wnl.0000261245.36884.7c

Cited by 41 publications

(25 citation statements)

References 25 publications

(33 reference statements)

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“…It has been previously shown that IENFD does regenerate in the setting of HIV infection, but was slowed 30 . Loss of IENFD in the SIV-infected CD8 depleted macaque model occurs early after infection (dpi 8-21) and never recovers to the baseline level 4 .…”

Section: Discussionmentioning

confidence: 99%

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

et al. 2017

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Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU-pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

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Section: Discussionmentioning

confidence: 99%

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

et al. 2017

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“…The diminution and degeneration of epidermal nerve fibers as seen in skin biopsies proves this hypothesis [6]. People with HIV infection have also significantly reduced rates of both collateral and regenerative sprouting in skin biopsy experimental injury models [27]. The presence of HIV-infected perivascular macrophages has been shown in the DRG of patients with and without DSP.…”

Section: Hiv-dspmentioning

confidence: 90%

HIV Associated Neuropathies

Hahn¹,

Husstedt²

2011

HIV Infection in the Era of Highly Active Antiretroviral Treatment and Some of Its Associated Complications

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“…Using this model, Polydefkis and colleagues showed that in diabetes, even without evidence of peripheral neuropathy there is a defect in sensory axonal regeneration and epidermal reinnervation [66]. Furthermore, they also demonstrated that a similar defect of regenerative capacity exists in patients with HIV [67]. Using the capsaicin-induced epidermal denervation model, they examined the potential regenerative effects of an immunophilin ligand, timcodar dimesylate [68].…”

Section: • • Capsaicin Denervationmentioning

confidence: 99%

Studying Axonal Degeneration and Regeneration Using In Vitro and In Vivo Models: the Translational Potential

Donaldson

Höke

2014

Future Neurol.

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Since the initial studies by Cajal, multiple models of peripheral nerve degeneration and regeneration have been developed to address the ever-increasing complexity of the mechanisms involved in regeneration. In vitro models offer the principal benefit of a system that can be readily manipulated to address specific mechanistic questions in a deconstructed system. However, in vitro models can be overly simplified and intricacies of the interactions between neurons and glia can be lost. In vivo animal models seek to remedy some of these shortcomings, but most in vivo animal systems fail to precisely model human nerve regeneration. Rodent models of chronic nerve regeneration have been developed to better recapitulate human nerve regeneration, but are not widely used. An important development in the field has been the establishment of experimental nerve regeneration in humans, involving the reinnervation of the epidermis after cutaneous axotomy or topical capsaicin application. Use of such human models will likely accelerate the development and evaluation of new drugs that enhance peripheral nerve regeneration. KeywordsGiven the complexity of the human peripheral nervous system, a wide spectrum of models has been developed over the years to advance the field of axonal degeneration and regeneration. Predominantly, these systems of neuronal degenerative and regenerative processes have been established in model organisms, particularly in rodents and occasionally in subhuman primates. These animal systems have significantly advanced the understanding of the molecular mechanisms of how axons degenerate and regenerate and have provided an initial subject to test novel drug therapies and surgical techniques to improve regeneration after human nerve injuries.In vitro animal models have served to simplify the field of study, reducing the variable factors that are inherently present in whole organism systems. With a range of methods available, there is the potential to study the interactions of neuronal and glial cell populations or with the advent of microtechnologies, to more precisely examine regeneration at the level of the individual axon. Narrowing the lens through which to view degeneration and regeneration, in vitro models permit a greater degree of manipulation and control of the microenvironment and the potential for rapid-paced drug-screening investigations.While in vitro techniques offer highly controllable systems of study, in vivo animal models provide a closer resemblance to the human condition of nerve injury and repair. Investigating the recovery process following nerve injury in living organisms permits a more authentic glimpse into regeneration as whole body system interactions are maintained. Preserving the integrity of the neuronal environment, in vivo animal nerve injury and repair methods model the complexity of the nervous system recovery, but lack some of the precision associated with in vitro methods.Developed over the last few decades, human models of regeneration emerged as a promising novel system t...

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Impaired reinnervation in HIV infection following experimental denervation

Cited by 41 publications

References 25 publications

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

HIV Associated Neuropathies

Studying Axonal Degeneration and Regeneration Using In Vitro and In Vivo Models: the Translational Potential

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