Comparison of effect of crush or transection peripheral nerve lesion on lumbar spinal cord synaptic plasticity and microglial dynamics

Campos, Raquel Maria Pereira; Barbosa-Silva, Maria Carolina; Ribeiro-Resende, Victor Túlio

doi:10.1016/j.ibneur.2021.05.002

Cited by 11 publications

(8 citation statements)

References 70 publications

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“…We previously reported that Ia-synapse deletion after nerve transection requires the C-C chemokine receptor type 2 (CCR2) and activation of ventral microglia dependent on colony-stimulating factor type 1 (CSF1/M-CSF) released from axotomized motoneurons. 8 Microgliosis after nerve crush injury appears initially similar, 21 but here we report that microglia remain activated for longer after nerve transection due to extended CSF1 expression in regenerating motoneurons. This causes a phenotypic switch in microglia toward expression of C-C chemokine ligand type 2 (CCL2).…”

Section: Introductionmentioning

confidence: 61%

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Rotterman,

Haley-Johnson,

Pottorf

et al. 2024

Cell Reports

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Section: Introductionmentioning

confidence: 61%

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Rotterman,

Haley-Johnson,

Pottorf

et al. 2024

Cell Reports

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“…Comparison of microglia in nerve cut versus crush in the adult rat showed that microglia activation is similar during the first 2 weeks postinjury but differs at later time points because of a prolongation of microglia activation after nerve cut ( He et al, 1996 ; Campos et al, 2021 ). We obtained similar results in adult mice ( Rotterman et al, 2019 ), and indeed the prolonged microglia activation correlated with infiltration of blood-borne CCR2 cells after nerve transection, but not after nerve crush, and the time course of immune cell infiltration correlated with the disappearance of VGluT1 synapses from the ventral horn ( Rotterman et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Comparison of microglia in nerve cut vs crush in the adult rat showed that microglia activation is similar during the first two weeks postinjury but differs at later time points because of a prolongation of microglia activation after nerve cut (He et al, 1996;Campos et al, 2021).…”

Section: Neuroinflammation After Neonatal Nerve Crush Differs From Adultmentioning

confidence: 99%

Massive Loss of Proprioceptive Ia Synapses in Rat Spinal Motoneurons after Nerve Crush Injuries in the Postnatal Period

Arbat-Plana

Bolívar²,

Navarro³

et al. 2023

eNeuro

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Peripheral nerve injuries (PNI) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from a-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. This goal was to analyze vesicular glutamate transporter 1 (VGLUT1) labeled Ia synapses (which might also include II afferents) after nerve crush in 10 day old Sprague Dawley rats, a PNI causing little Ia/II synapse loss in adult. We confirmed fast and efficient reinnervation of leg muscles, however a massive number of VGLUT1/Ia/II synapses were permanently lost. This synapse loss was similar to that after more severe nerve injuries involving full transection in adults. In adults, disappearance of ventrally directed Ia/II collaterals targeting α-motoneurons was associated with a prolonged microglia reaction and a CCR2 mechanism that included infiltration of CCR2 blood immune cells. By contrast, microgliosis after p10 injuries was fast, resolved in about a week, and there was no evidence of peripheral immune cell infiltration. We conclude that VGLUT1/Ia/II synapse loss in young animals differs in mechanism, perhaps associated with higher microglia synaptic pruning activity at this age and results in larger losses after milder nerve injuries.Significance statementSynaptic plasticity in spinal motor circuits induced by nerve injuries can be rather permanent and hinder motor and sensory function recovery, even when experimental manipulations are designed for fast and efficient regeneration and target innervation. One input particularly affected is the Ia afferent synapse on α-motoneurons. The degree of loss of this input depends on injury severity and correlates with varying efficiencies while reinnervating peripheral targets. In here we demonstrate that the loss is also age dependent, being higher in the young. The enhanced synaptic pruning capabilities of microglia during critical windows of high synaptic plasticity at early age, might contribute to augment synaptic circuit reorganizations.

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“…1 Crush injuries are typified with more rapid recovery of at least partial if not total motor and sensory control by day 7 to 21 46 in the mouse despite similar processes including Wallerian degeneration of the distal stump and microglial reactivity in the acute period. 1,20…”

Section: Nerve Regeneration After Peripheral Nerve Injuriesmentioning

confidence: 99%

Biology and pathophysiology of symptomatic neuromas

Hwang,

Hoftiezer,

Raasveld

et al. 2023

Pain

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Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation—as well as the resulting neuropathic pain—remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.

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Comparison of effect of crush or transection peripheral nerve lesion on lumbar spinal cord synaptic plasticity and microglial dynamics

Cited by 11 publications

References 70 publications

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia

Massive Loss of Proprioceptive Ia Synapses in Rat Spinal Motoneurons after Nerve Crush Injuries in the Postnatal Period

Biology and pathophysiology of symptomatic neuromas

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