Liposome-encapsulated clodronate specifically depletes spinal microglia and reduces initial neuropathic pain

Wang, Yi-Rui; Mao, Xiao-Fang; Wu, Haiyun; Wang, Yongxiang

doi:10.1016/j.bbrc.2018.03.177

Cited by 36 publications

(18 citation statements)

References 43 publications

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“…However, this has not been confirmed in other studies using different approaches to deplete microglia (Gowing et al, ; Spiller et al, ). A beneficial outcome of microglial depletion is also evident in neuropathic pain by reducing the expression of pro‐inflammatory cytokines (Lee, Shi, Fan, West, & Zhang, ), which was also confirmed in another study (Wang, Mao, Wu, & Wang, ).…”

Section: Depleting Microglia In Diseases: the Friend In Need May Not supporting

confidence: 64%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

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Microglia are prominent immune cells in the central nervous system (CNS) and are critical players in both neurological development and homeostasis, and in neurological diseases when dysfunctional. Our previous understanding of the phenotypes and functions of microglia has been greatly extended by a dearth of recent investigations. Distinct genetically defined subsets of microglia are now recognized to perform their own independent functions in specific conditions. The molecular profiling of single microglial cells indicates extensively heterogeneous reactions in different neurological disorders, resulting in multiple potentials for crosstalk with other kinds of CNS cells such as astrocytes and neurons. In settings of neurological diseases it could thus be prudent to establish effective cell‐based therapies by targeting entire microglial networks. Notably, activated microglial depletion through genetic targeting or pharmacological therapies within a suitable time window can stimulate replenishment of the CNS niche with new microglia. Additionally, enforced repopulation through provision of replacement cells also represents a potential means of exchanging dysfunctional with functional microglia. In each setting the newly repopulated microglia might have the potential to resolve ongoing neuroinflammation. In this review, we aim to summarize the most recent knowledge of microglia and to highlight microglial depletion and subsequent repopulation as a promising cell replacement therapy. Although glial cell replacement therapy is still in its infancy and future translational studies are still required, the approach is scientifically sound and provides new optimism for managing the neurotoxicity and neuroinflammation induced by activated microglia.

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Section: Depleting Microglia In Diseases: the Friend In Need May Not supporting

confidence: 64%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

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“…When LEC is administered centrally (brain and spinal cord), it specifically depletes microglia (which are the "CNS equivalent" of macrophages; Drabek et al, 2012). Spinal administration of LEC blocked the development or initiation of neuropathic pain, while it did not affect neuropathic pain that had already developed before BJP administration (Wang et al, 2018). This is consistent with the findings from other studies using minocycline to deplete microglia (Raghavendra, Tanga, & DeLeo, 2003), suggesting that microglia activation may play an important role in the early phases after nerve injury and the development of central sensitization and neuropathic pain, while they play a lesser role in the maintenance of the neuropathic state, which may be more related to a delayed, sequential activation of spinal astroglia (Gwak, Kang, Unabia, & Hulsebosch, 2012;Mika et al, 2009).…”

Section: Effects Related To Microglia Inhibition Resulting In Decrementioning

confidence: 99%

Section: Effects Related To Microglia Inhibition Resulting In Decrementioning

confidence: 99%

“…One might thus speculate that if peripheral macrophages/microglia are depleted by bisphosphonate treatment, this may also affect the number of activated or activatable microglia in the spinal cord. Notwithstanding the question of how bisphosphonates may enter the CNS after systemic administration, the efficacy of intracerebroventricularly administered clodronate and etidronate (Kim et al, 2013) and of intrathecally administered clodronate (Wang et al, 2018) suggests that analgesic targets of bisphosphonate are present in the CNS and that interaction with these central targets is sufficient to produce an analgesic effect.…”

Section: Central Versus Peripheral Effectsmentioning

confidence: 99%

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Pharmacology of bisphosphonates in pain

Tzschentke

2019

British J Pharmacology

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“…After a nerve lesion, macrophages infiltrate the area of Wallerian degeneration. Intravenous injection of clodronate encapsulated in liposomes reduced the number of macrophages in the injured nerves, alleviated thermal hyperalgesia, and protected myelinated, as well as unmyelinated fibers against degeneration [ 13 ]. In parallel to or following macrophage recruitment, T cells also infiltrate into damaged nerves.…”

Section: Role Of Immune Cells In Npmentioning

confidence: 99%

Stem Cell Therapy for Modulating Neuroinflammation in Neuropathic Pain

Joshi

Kim

et al. 2021

IJMS

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Neuropathic pain (NP) is a complex, debilitating, chronic pain state, heterogeneous in nature and caused by a lesion or disease affecting the somatosensory system. Its pathogenesis involves a wide range of molecular pathways. NP treatment is extremely challenging, due to its complex underlying disease mechanisms. Current pharmacological and nonpharmacological approaches can provide long-lasting pain relief to a limited percentage of patients and lack safe and effective treatment options. Therefore, scientists are focusing on the introduction of novel treatment approaches, such as stem cell therapy. A growing number of reports have highlighted the potential of stem cells for treating NP. In this review, we briefly introduce NP, current pharmacological and nonpharmacological treatments, and preclinical studies of stem cells to treat NP. In addition, we summarize stem cell mechanisms—including neuromodulation in treating NP. Literature searches were conducted using PubMed to provide an overview of the neuroprotective effects of stem cells with particular emphasis on recent translational research regarding stem cell-based treatment of NP, highlighting its potential as a novel therapeutic approach.

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Liposome-encapsulated clodronate specifically depletes spinal microglia and reduces initial neuropathic pain

Cited by 36 publications

References 43 publications

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Pharmacology of bisphosphonates in pain

Stem Cell Therapy for Modulating Neuroinflammation in Neuropathic Pain

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