Toll-like receptor 4 (TLR4) influences the glial reaction in the spinal cord and the neural response to injury following peripheral nerve crush

Ribeiro, Patrícia; Castro, Mateus Vidigal de; Perez, Matheus; Cartarozzi, Luciana Politti; Spejo, Aline Barroso; Chiarotto, Gabriela Bortolança; Augusto, Taize Machado; Oliveira, Alexandre Leite Rodrigues de

doi:10.1016/j.brainresbull.2019.11.008

Cited by 18 publications

(12 citation statements)

References 25 publications

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“…Activation of TLR 4 resulted in a delay in functional recovery after sciatic nerve injury in mice. 20 – 22 TLR 1 showed an expression pattern similar to that of TLR 4 in our study. According to a study that analyzed TLR 1–9 expression in Schwann cells from mice, all TLRs 1–9 were expressed, but TLR 1 expression was especially increased after nerve injury.…”

Section: Discussionsupporting

confidence: 82%

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury

Min

Kim

Lee

et al. 2022

Int J Immunopathol Pharmacol

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Objectives: This study aimed to determine whether toll-like receptor expression patterns differ in the distal facial nerve during recovery after crushing and cutting injuries. Methods: Adult male Sprague-Dawley rats underwent crushing or cutting injury of the unilateral facial nerve. Their whisker movement and blink reflex were examined. Western blotting was performed with the normal nerve on the left side and the damaged nerve on the right side, four days, 14 days, and 3 months after injury. Results: The scores of whisker movements and blink reflex in the crushing group showed improvements, while the score of the cutting group was significantly lower at 14 days and 3 months (p < 0.05). Western blotting showed that TLRs 11 and 13 increased in the crushing group, and TLRs 1, 2, 3, 4, 5, 8, 10, 11, 12, and 13 increased in the cutting group after 14 days ( p < 0.05). After 3 months, TLRs 10 and 11 increased in the crushing group, and TLRs 1, 4, 5, 8, 11, and 12 increased in the cutting group ( p < 0.05). Conclusion: TLRs 1, 4, 5, 8, and 12 are related to nerve degeneration after facial nerve injury, and TLRs 10, 11, and 13 are related to recovery from facial palsy.

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Section: Discussionsupporting

confidence: 82%

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury

Min

Kim

Lee

et al. 2022

Int J Immunopathol Pharmacol

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“…Astrocytic reactions vary with mouse strain: A/J mice show stronger reactions around axotomized motoneurons compared to C57BL/6J mice and this is correlated with fewer synapses after axotomy and impaired recovery (Emirandetti et al, 2006). Mutant mice with variations in astrocytosis levels after nerve injury showed co-related variations in the amount of synaptic loss (Victorio et al, 2010;Freria et al, 2012;Ribeiro et al, 2019). A more definitive study for proving causality used transection of the facial nerve and blocked the astrocytic reaction by astrocyte-specific deletion of STAT3 (Tyzack et al, 2014).…”

Section: Role Of Astrocytes In Synaptic Remodeling Around Axotomized mentioning

confidence: 99%

Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

Álvarez

Rotterman

Akhter

et al. 2020

Front. Mol. Neurosci.

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Motoneurons axotomized by peripheral nerve injuries experience profound changes in their synaptic inputs that are associated with a neuroinflammatory response that includes local microglia and astrocytes. This reaction is conserved across different types of motoneurons, injuries, and species, but also displays many unique features in each particular case. These reactions have been amply studied, but there is still a lack of knowledge on their functional significance and mechanisms. In this review article, we compiled data from many different fields to generate a comprehensive conceptual framework to best interpret past data and spawn new hypotheses and research. We propose that synaptic plasticity around axotomized motoneurons should be divided into two distinct processes. First, a rapid cell-autonomous, microglia-independent shedding of synapses from motoneuron cell bodies and proximal dendrites that is reversible after muscle reinnervation. Second, a slower mechanism that is microgliadependent and permanently alters spinal cord circuitry by fully eliminating from the ventral horn the axon collaterals of peripherally injured and regenerating sensory Ia afferent proprioceptors. This removes this input from cell bodies and throughout the dendritic tree of axotomized motoneurons as well as from many other spinal neurons, thus reconfiguring ventral horn motor circuitries to function after regeneration without direct sensory feedback from muscle. This process is modulated by injury severity, suggesting a correlation with poor regeneration specificity due to sensory and motor axons targeting errors in the periphery that likely render Ia afferent connectivity in the ventral horn nonadaptive. In contrast, reversible synaptic changes on the cell bodies occur only while motoneurons are regenerating. This cell-autonomous process displays unique features according to motoneuron type and modulation by local microglia and astrocytes and generally results in a transient reduction of fast synaptic activity that is probably replaced by embryonic-like slow GABA depolarizations, proposed to relate to regenerative mechanisms.

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“…In contrast, the ventral microglia response around axotomized MNs after PNI (sciatic nerve transection) seems unaffected in TLR2 or TLR4 knockouts [126]. Nevertheless, exogenous TLR4 activation significantly alters microglia around MNs, and preconditioning spinal microglia by systemic LPS exacerbates the microglia reaction around axotomized MNs after sciatic nerve crush [127]. It also protected lumbar and thoracic MNs from ischemic damage after aortic occlusion [128].…”

Section: Toll-like Receptors (Tlrs)mentioning

confidence: 99%

The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury

Pottorf

Rotterman

McCallum

et al. 2022

Cells

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Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function of microgliosis around injured motoneurons and sensory afferents. Herein, we provide a comparative analysis of the dorsal and ventral horns in relation to mechanisms of microglia activation (CSF1, DAP12, CCR2, Fractalkine signaling, Toll-like receptors, and purinergic signaling), and functionality in neuroprotection, degeneration, regeneration, synaptic plasticity, and spinal circuit reorganization following peripheral nerve injury. This review aims to shed new light on unsettled controversies regarding the diversity of spinal microglial-neuronal interactions following injury.

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Toll-like receptor 4 (TLR4) influences the glial reaction in the spinal cord and the neural response to injury following peripheral nerve crush

Cited by 18 publications

References 25 publications

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury

Relationship between toll-like receptor expression in the distal facial nerve and facial nerve recovery after injury

Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury

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