RhoA Inhibitor Treatment At Acute Phase of Spinal Cord Injury May Induce Neurite Outgrowth and Synaptogenesis

Devaux, Stéphanie; Cizkova, Dasa; Mallah, Khalil; Karnoub, Mélodie‐Anne; Laouby, Zahra; Kobeissy, Firas; Blasko, Juraj; Nataf, Serge; Pays, Laurent; Meriaux, Céline; Fournier, Isabelle

doi:10.1074/mcp.m116.064881

Cited by 25 publications

(49 citation statements)

References 53 publications

(45 reference statements)

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“…Some NSAIDS, primarily ibuprofen and indomethacin, reduce the activity of RhoA both in vitro and in vivo . Ibuprofen, specifically, improves axonal outgrowth and restoration of synapses, increases axonal myelination, and reduces apoptosis via RhoA inhibition after SCI, with concurrent improvement of neurological function in rats . Although meloxicam does not directly reduce RhoA activity in cell cultures, an indirect modulatory effect of COX inhibitors in vivo limiting the molecular cascade and inflammatory cycle leading to the activation of RhoA, cannot be excluded .…”

Section: Discussionmentioning

confidence: 99%

Predictors of urinary or fecal incontinence in dogs with thoracolumbar acute non‐compressive nucleus pulposus extrusion

Mari

Behr

Shea

et al. 2019

Veterinary Internal Medicne

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Background: Urinary (UI) and fecal (FI) incontinence occur in up to 7.5% and 32% of dogs, respectively, after thoracolumbar acute noncompressive nucleus pulposus extrusion (ANNPE).Hypotheses/Objectives: To investigate clinical, diagnostic, and therapeutic predictors of UI and FI in dogs with ANNPE affecting the T3-L3 spinal cord segments.Animals: Hundred and eighty-seven dogs with T3-L3 ANNPE diagnosed based on clinical and MRI findings.Methods: Multicenter retrospective study. Data were obtained from medical records and telephone questionnaires and analyzed by logistic regression.Results: UI and FI were reported in 17 (9.1%) and 44 (23.5%) dogs, respectively. Paraplegic dogs were 3 times (95% CI = 1.25, 10.87) more likely to develop UI (P = .018) and 4 times (95% CI = 1.94, 12.56) more likely to develop FI (P = .001) compared to nonparaplegic dogs. Dogs with an intramedullary hyperintensity greater than 40% of the cross-sectional area of the spinal cord at the same level on transverse T2-weighted MRI images were 4 times more likely to develop UI (95% CI = 1.04, 21.72; P = .045) and FI (95% CI = 1.56, 10.39; P = .004) compared to dogs with smaller lesions. FI was 3 times (95% CI = 1.41, 7.93) more likely in dogs that were not treated with nonsteroidal anti-inflammatory drugs (NSAIDs) after diagnosis compared to dogs administered NSAIDs (P = .006) and 2 times (95% CI = 1.12, 5.98) more likely in dogs presented with clinical signs compatible with spinal shock compared to dogs without (P = .026).Abbreviations: ANNPE, acute non-compressive nucleus pulposus extrusion; COX2, cyclooxygenase-2; FI, fecal incontinence; LL:VL, ratio of the length of the intramedullary lesion to the length of the L2 vertebra; NSAIDs, nonsteroidal anti-inflammatory drugs;PCSAL, percentage of the cross-sectional spinal cord area occupied by the lesion; SCI, spinal cord injury; UI, urinary incontinence.

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Section: Discussionmentioning

confidence: 99%

Predictors of urinary or fecal incontinence in dogs with thoracolumbar acute non‐compressive nucleus pulposus extrusion

Mari

Behr

Shea

et al. 2019

Veterinary Internal Medicne

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“…Traumatic SCI can lead to paralysis with complete or partial loss of neurological functions below the injury site, and this can result from several different causes such as road traffic crashes, falls, and violence 1 . Nowadays, the increased incidence of trauma may be related to popular sports such as ice hockey, American football, rugby, horse riding and diving 2 , 3 . Currently, there are no effective therapies available for SCI patients.…”

Section: Introductionmentioning

confidence: 99%

“…A key factor for effective therapy is elucidation of the distinct phases involved in SCI and the cellular and molecular events underlying them 3 . Diverse groups of cells and molecules from the nervous, immune, and vascular systems are implicated.…”

Section: Introductionmentioning

confidence: 99%

3D MALDI mass spectrometry imaging reveals specific localization of long-chain acylcarnitines within a 10-day time window of spinal cord injury

Quanico

Hauberg‐Lotte

Devaux

et al. 2018

Sci Rep

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We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). Acylcarnitines palmitoylcarnitine (AC(16:0)), palmitoleoylcarnitine (AC(16:1)), elaidic carnitine (AC(18:1)) and tetradecanoylcarnitine (AC(14:1)) were detected as early as 3 days post injury, and were present along the lesion margins 7 and 10 days after SCI induced by balloon compression technique in the rat. 3D MSI revealed the heterogeneous distribution of these lipids across the injured spinal cord, appearing well-defined at the lesion margins rostral to the lesion center, and becoming widespread and less confined to the margins at the region located caudally. The assigned acylcarnitines co-localize with resident microglia/macrophages detected along the lesion margins by immunofluorescence. Given the reported pro-inflammatory role of these acylcarnitines, their specific spatial localization along the lesion margin could hint at their potential pathophysiological roles in the progression of SCI.

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“…In the light of the current knowledge, members of the RhoA subfamily of GTPases represent attractive candidates. For example, current studies focus on the therapeutic inhibition of RhoA, which is correlated with an enhanced neuronal survival and axon regeneration after lesion [65][66][67][68][69]. Progress in this research field may help to develop new therapies and strategies to treat CNS lesions.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the Nucleotide Exchange Factor Vav3 Enhances Axonal Complexity and Synapse Formation but Tampers Activity of Hippocampal Neuronal Networks In Vitro

Wegrzyn

Tedford

et al. 2020

IJMS

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Vav proteins activate GTPases of the RhoA subfamily that regulate the cytoskeleton and are involved in adhesion, migration, differentiation, polarity and the cell cycle. While the importance of RhoA GTPases for neuronal morphology is undisputed, their regulation is less well understood. In this perspective, we studied the consequences of the deletion of Vav2, Vav3 and Vav2 and 3 (Vav2−/−, Vav3−/−, Vav2−/−/3−/−) for the development of embryonic hippocampal neurons in vitro. Using an indirect co-culture system of hippocampal neurons with primary wild-type (WT) cortical astrocytes, we analysed axonal and dendritic parameters, structural synapse numbers and the spontaneous network activity via immunocytochemistry and multielectrode array analysis (MEA). Here, we observed a higher process complexity in Vav3−/−, but not in Vav2−/− neurons after three and five days in vitro (DIV). Furthermore, an enhanced synapse formation was observed in Vav3−/− after 14 days in culture. Remarkably, Vav2−/−/3−/− double knockout neurons did not display synergistic effects. Interestingly, these differences were transient and compensated after a cultivation period of 21 days. Network analysis revealed a diminished number of spontaneously occurring action potentials in Vav3−/− neurons after 21 DIV. Based on these results, it appears that Vav3 participates in key events of neuronal differentiation.

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RhoA Inhibitor Treatment At Acute Phase of Spinal Cord Injury May Induce Neurite Outgrowth and Synaptogenesis

Cited by 25 publications

References 53 publications

Predictors of urinary or fecal incontinence in dogs with thoracolumbar acute non‐compressive nucleus pulposus extrusion

Predictors of urinary or fecal incontinence in dogs with thoracolumbar acute non‐compressive nucleus pulposus extrusion

3D MALDI mass spectrometry imaging reveals specific localization of long-chain acylcarnitines within a 10-day time window of spinal cord injury

Deletion of the Nucleotide Exchange Factor Vav3 Enhances Axonal Complexity and Synapse Formation but Tampers Activity of Hippocampal Neuronal Networks In Vitro

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