Yannick Gerber

University of Montpellier, Montpellier, France · Institute for Neurosciences (INM)

Traumatic spinal cord injury (SCI) induces irreversible autonomic and sensory-motor impairments. A large number of patients exhibit chronic SCI and no curative treatment is currently available. Microglia are predominant immune players after SCI, they undergo highly dynamic processes, including proliferation and morphological modification. In a tran...

Spinal cord injury is a dramatic disease leading to severe motor, sensitive and autonomic impairments. After injury the axonal regeneration is partly inhibited by the glial scar, acting as a physical and chemical barrier. The scarring process involves microglia, astrocytes and extracellular matrix components, such as collagen, constructing the fibr...

Spinal cord injury (SCI) leads to persistent neurological deficits without available curative treatment. After SCI astrocytes within the lesion vicinity become reactive, these undergo major morphological, and molecular transformations. Previously, we reported that following SCI, over 10% of resident astrocytes surrounding the lesion spontaneously t...

Microglia are major players in scar formation after an injury to the spinal cord. Microglia proliferation, differentiation, and survival are regulated by the colony-stimulating factor 1 (CSF1). Complete microglia elimination using CSF1 receptor (CSF1R) inhibitors worsens motor function recovery after spinal injury (SCI). Conversely, a 1-week oral t...

The glial scar that forms after traumatic spinal cord injury (SCI) is mostly composed of microglia, NG2 glia, and astrocytes and plays dual roles in pathophysiological processes induced by the injury. On one hand, the glial scar acts as a chemical and physical obstacle to spontaneous axonal regeneration, thus preventing functional recovery, and, on...

Many histological techniques are used to identify and characterize myelin in the mammalian nervous system. Due to the high content of lipids in myelin sheaths, coherent anti-stokes Raman scattering (CARS) microscopy is a label-free method that allows identifying myelin within tissues. CARS excites the CH 2 vibrational mode at 2845 cm ⁻¹ and CH 2 bo...

No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia prolifer...

No curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery. In a translational objective, we investigated whether a transient pharmacological reduction of microglia prolifera...

In traumatic spinal cord injury, the initial trauma is followed by a cascade of impairments, including excitotoxicity and calcium overload, which ultimately induces secondary damages. The sigma-1 receptor is widely expressed in the central nervous system and is acknowledged to play a key role in calcium homeostasis. Treatments with agonists of the...

Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by activation and proliferation of resident microglia as well as infiltrating peripheral monocyte-derived macrophages. Depending on the time post-lesion, positive and detrimental influences of microglia/macrophages on axonal regeneration had been reported after SCI, raising the...

GFAP immunostaining in untreated and GW2580-treated mice at 6 weeks after SCI. GFAP immunostainings rostral (A,D,G,J), within (B,E,H,K) and caudal (C,F,I,L) to the lesion epicenter in untreated (A–C,G–I) mice and in GW2580-treated (D–F,J–L) mice at 6 weeks after SCI. Higher magnification in untreated (G–I) and GW2580-treated mice (J–L) are correspo...

Microglia proliferation in GW2580-treated and untreated mice: cell distribution in the spinal cord. Densities of eGFP-positive cells (microglia; A–C), BrdU-positive cells (proliferative cells; D–F) and BrdU/eGFP-positive cells (proliferative microglia; G–I) from the spinal cord of untreated and GW2580-treated mice. Quantifications were done at the...

GW2580 inhibits microglia proliferation in the mouse spinal cord at 2 weeks after SCI. Fluorescent micrographs of axial spinal cord sections from CX3CR1+/eGFP mice. Microglia eGFP-positive cells (A,D,G,J,M,P), BrdU staining (B,E,H,K,N,Q) and merged (C,F,I,L,O,R). Axial sections from untreated (A–I) and GW2580-treated mice (J–R) at 2 weeks after SCI...

Ex vivo MRI and histological assessments of the lesion size in untreated and GW2580-treated mice at 2 weeks after SCI. Ex vivo axial T2-weighted MRI quantification of the lesion area, lesion extension and volume in untreated and GW2580-treated groups (A–C). Toluidine Blue stained axial sections quantification of the lesion area, lesion extension an...

IBA1 immunostaining in untreated and GW2580-treated mice at 2 weeks after SCI. Brightfield micrographs representing IBA1 immunostainings rostral (A,D,G,J), within (B,E,H,K) and caudal (C,F,I,L) to the lesion epicenter in untreated mice (A–C,G–I) and in GW2580-treated mice (D–F,J–L) at 2 weeks after SCI. Higher magnification in untreated (G–I) and G...

IBA1 immunostaining in untreated and GW2580-treated mice at 6 weeks after SCI. IBA1 immunostainings rostral (A,D,G,J), within (B,E,H,K) and caudal (C,F,I,L) to the lesion epicenter in untreated mice (A–C,G–I) and in GW2580-treated mice (D–F,J–L) at 6 weeks after SCI. Higher magnification in untreated (G–I) and GW2580-treated mice (J–L) are correspo...

GFAP immunostaining in untreated and GW2580-treated mice at 2 weeks after SCI. Brightfield micrographs representing GFAP immunostainings rostral (A,D,G,J), within (B,E,H,K) and caudal (C,F,I,L) to the lesion epicenter in untreated (A–C,G–I) mice and in GW2580-treated (D–F,J–L) mice at 2 weeks after SCI. Higher magnification in untreated (G–I) and G...

Microtubule-associated protein tau aggregates constitute the characteristic neuropathological features of several neurodegenerative diseases grouped under the name of tauopathies. It is now clear that the process of tau aggregation is associated with neurodegeneration. Several transgenic tau mouse models have been developed where tau progressively...

Microtubule-associated protein tau aggregates constitute the characteristic neuropathological features of several neurodegenerative diseases grouped under them name of tauopathies. It is now clear that the process of tau aggregation is associated with neurodegeneration. Several transgenic tau mouse models have been developed where tau progressively...

Neurons have inherent competence to regrow following injury, although not spontaneously. Spinal cord injury (SCI) induces a pronounced neuroinflammation driven by resident microglia and infiltrating peripheral macrophages. Microglia are the first reactive glial population after SCI and participate in recruitment of monocyte-derived macrophages to t...

Specific microgial transcript over-expression after SCI in CX3CR1+/eGFP mice. Bar graphs displaying specific over-expression of microglia-specific transcripts at different stages after HS (A). Values are actual fold change. Bar graphs indicating up-regulation of Serpina3n transcript expressions in microglia at different time-point after HS and FT S...

Induction of neural development pathways in microglia after SCI. Gene ontology pathway map analysis displaying the induction of neural development pathway in microglia after SCI. Thermometers indicate deregulated genes (red: up-regulated; blue: down-regulated). Interactions between objects: green (positive or activation); red (negative or inhibitio...

Database of differential expression comparison of activated microglia RNA-Seq data relative to non-injured control microglia at 72 h, 1 and 2 weeks after hemisection and full transection injuries.

Specific microglial eGFP expression in CX3CR1+/eGFP mice spinal cord. Schematic drawing of longitudinal spinal cords from either non-injured control or following FT. The red square illustrates the lesion site and reference frames display on the field of views. Confocal micrographs showing microglial eGFP expression in non-injured CX3CR1+/eGFP mice...

Flow cytometry analysis. Representative flow cytometry analysis dot plots displaying control (A) and eGFPhigh-expressing microglia profiles from non-injured (B) as well as after HS (C) and FT SCI (D). Surrounded areas, designed as “P4” represent sorted cells that correspond to the eGFPhigh-expressing cells further analyzed using RNAseq. The X- and...

Increased IBA1 reactivity 3 months after SCI in Microcebus murinus. Bright field micrographs displaying IBA1-positive microglia rostral (A–C), within (D–F) and caudal (G–I) to the lesion site at 3 months following spinal cord hemisection in Microcebus murinus. Note similar to BRCA1 immunostaining adjacent sections stained with IBA1 displayed identi...

Database of the expression level of cellular markers (microglia, neuronal, astrocyte and oligodendrocyte). Differentially expressed genes amongst these cellular markers, data relative to non-injured control microglia at 72 h, 1 and 2 weeks after hemisection and full transection injuries. FC, Fold change; FDR, false discovery rate.

Microglia responses after SCI are time-dependent irrespective of lesion severity. Schematic diagram displaying the multiple comparisons carried out to analyze deregulated genes in microglia at multiple time-points after HS and FT SCI (A). Table illustrating the number of deregulated transcripts in each comparisons (B). Note that no deregulated gene...

Pathway analysis of differentially expressed genes in activated microglia after hemisection and full transection injuries.

Background: Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise...

Background Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise...

Abstract BACKGROUND: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. RESULTS: To identify candidate genes that may be involved...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typified by a massive loss of motor neurons with few therapeutic options. The exact cause of neuronal degeneration is unknown but it is now admitted that ALS is a multifactorial disease with several mechanisms involved including glutamate excitotoxicity. More specifically, N-...

Amyotrophic lateral sclerosis (ALS) is characterized by a gradual muscular paralysis resulting from progressive motoneurons death. ALS etiology remains unknown although it has been demonstrated to be a multifactorial disease involving several cellular partners. There is currently no effective treatment. Even if the effect of exercise is under inves...

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by selective motoneurons degeneration. There is today no clear-cut pathogenesis sequence nor any treatment. However growing evidences are in favor of the involvement, besides neurons, of several partners such as glia and muscles. To better characterize th...

FACS analysis of GFAP+ astrocytes in control and hSOD1G93A mice spinal cords. (A–C) - Representative flow cytometry analysis dot plot astrocyte profiles at P30. A - Negative control (without GFAP staining). B - Control and C - hSOD1G93A spinal astrocytes. (E–G) - Representative flow cytometry analysis dot plot astrocyte profiles at P60. E - Negativ...

Weight modifications in control and hSOD1G93A mice. Weight changes in control (red) and hSOD1G93A (green) mice were weekly recorded from P56 to the end of the life of the transgenic mice. Statistical analysis: data are expressed as means ± standard error of the mean (SEM), t-test, * p<0.05, ** p<0.01, *** p<0.001. (TIF)

FACS analysis of astrocytes in control and hSOD1G93A mice spinal cords at pre-symptomatic age. The number of spinal astrocytes from hSOD1G93A animals and their control littermates was assessed by flow cytometry using the pan-astrocyte marker Aldh1L1. (A–C) - Representative flow cytometry analysis dot plot astrocyte profiles. A - Negative control (w...

Serotonergic innervation of the spinal cord in mammals has multiple roles in the control of motor, sensory and visceral functions. In rats, functional consequences of spinal cord injury at thoracic level can be improved by a substitutive transplantation of serotonin (5-HT) neurons or regeneration under the trophic influence of grafted stem cells. T...

Résumé. Les pathologies du système nerveux, qu'elles soient d'origine traumatique, vasculaire ou dégénérative, sont caractérisées par des pertes cellulaires et/ou l'interruption des circuits neuronaux. À l'heure actuelle, la majorité des approches thérapeutiques est de nature plus symptomatique que curative. La mise en évidence récente de cellules...