Florence Perrin

University of Montpellier, France. INSERM. Institut Universtaire de France.

In this study, we aimed to determine the impact of an increase in motor activity during the highly plastic period of development of the motor spinal cord and hindlimb muscles in newborn mice. A swim training regimen, consisting of two sessions per day for two days, was conducted in 1 and 2-day-old (P1, P2) pups. P3-trained pups showed a faster acqu...

Spinal cord injury results in significant sensorimotor deficits, currently, there is no curative treatment for the symptoms induced by spinal cord injury. Basic and pre-clinical research on spinal cord injury relies on the development and characterization of appropriate animal models. These models should replicate the symptoms observed in human, al...

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...

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and noncell-autonomous mechanisms lead to the selective degeneration of motoneurons (MN). Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1G93A protein. An AAV-gfaABC...

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...

Ependymal cells reside in the adult spinal cord and display stem cell properties in vitro. They proliferate after spinal cord injury and produce neurons in lower vertebrates but predominantly astrocytes in mammals. The mechanisms underlying this glial-biased differentiation remain ill-defined. We addressed this issue by generating a molecular resou...

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...

We demonstrated the presence of neural stem cells and/or progenitor cells in the adult human spinal cord. This chapter provides materials and methods to harvest high-quality samples of thoracolumbar, lumbar, and sacral adult human spinal cord and human dorsal root ganglia isolated from brain-dead patients who had agreed before passing to donate the...

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...

Ependymal cells reside in the adult spinal cord around the central canal and have stem cell properties in vitro. They rapidly activate and proliferate after spinal cord injury, constituting a source of new cells. They produce neurons and glial cells in lower vertebrates but they mainly generate glial cells in mammals. The mechanisms underlying thei...

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...

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and non-cell-autonomous mechanisms lead to the selective degeneration of motoneurons. Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1G93A protein. An AAV-gfaABC1D v...

Spinal cord injury (SCI) causes temporary disabilities or permanent effects including neuropathic pain and spastiscity. The damage often results from mechanical trauma, which in turn triggers the neuroinflammatory process. Neuroinflammation plays essential roles in the structural, biochemical, and cellular changes that take place in the spinal cord...

Anamniotes, rodents, and young humans maintain neural stem cells in the ependymal zone (EZ)around the central canal of the spinal cord, representing a possible endogenous source for repair in mammalian lesions. Cell diversity and genes specific for this region are ill defined. A cellular and molecular resource is provided here for the mouse and hum...

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...

Astrogliosis within the lesion site in Swiss Webster and C57BL/6 mice after severe SCI. Confocal photomicrographs indicating vimentin staining in the NI control and transected longitudinal spinal cord sections (A,B). Bar graphs indicating quantitative analysis of vimentin immunoreactivity at different stages after spinal cord transection (C,D). Tra...

Schematic drawing of the longitudinal spinal cord sections from non-injured (NI) control and after complete spinal cord injury (SCI) illustrating the lesion site (red rectangle) and five zones (Z1–Z5) of 250 μm width used for measuring glial reactivity (A). Photomicrographs indicating the experimental arrangement of open field and sandpaper tests u...

Swiss Webster and C57BL/6 mice display similar anxiety behavior after spinal cord transection. Bar graphs displaying alterations in anxiety behavior after complete transection of the spinal cord in Swiss Webster (A) and C57BL/6 mice (B). Both Swiss Webster and C57BL/6 mice displayed similar increase in anxiety behavior after SCI throughout 6 weeks...

Differential glial response in Swiss Webster and C57BL/6 mice after severe SCI. Bar graphs indicating quantitative analysis of IBA1 area fraction along the five zones rostral and caudal to the lesion site in Swiss Webster (A,D) and C57BL/6 mice (B,E). Direct comparisons revealed that spinal cord transected Swiss Webster displayed increased IBA1 are...

Spinal cord injuries (SCI) are disastrous neuropathologies causing permanent disabilities. The availability of different strains of mice is valuable for studying the pathophysiological mechanisms involved in SCI. However, strain differences have a profound effect on spontaneous functional recovery after SCI. CX3CR1+/eGFP and Aldh1l1-EGFP mice that...

Spinal cord injuries (SCI) are neuropathologies causing enormous physical and emotional anguish as well as irreversibly disabilities with great socio/economic burdens to our society. The availability of multiple mouse strains is important for studying the underlying pathophysiological response after SCI. Although strain differences have been shown...

Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile of nociceptors in normal conditions, little is known about how this profile changes in pathological conditions. In this study we exploited laser capture microd...

Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obsta...

In the last decade, the number of emerging Flaviviruses described worldwide has increased considerably. Among them Zika virus (ZIKV) and Usutu virus (USUV) are African mosquito-borne viruses that recently emerged. Recently, ZIKV has been intensely studied due to major outbreaks associated with neonatal death and birth defects, as well as neurologic...

Trypan blue assay (supernatant + adherent cells) showed that cell viability is not affected in USUV-infected astrocytes at 6 dpi at MOI of 0.1 and 2. Staurosporin-treated cells (1 μm for 6 hours) are used as cell death control. (***p<0.001). (TIF)

List of genes analyzed in the PCR array. (XLSX)

Ex vivo MRI assessments following SCI. Ex vivo T2 weighted images (B, D, F, H, and J) and diffusion MRI (A, C, E, G, and I) from the same mouse spinal cord rostral (A–D) within (E,F) and caudal (G–J) to the lesion epicenter (E–F). Panels (C,D) correspond to annotated images of (A,B); (I,J) correspond to annotated images of (G,H). Entire spinal cord...

A cleared spinal cord of an un-injured CX3CR1+/eGFP mouse imaged with two-photon microscopy to assess microglia/monocytes density. Clearing of the spinal cord substantially improves the depth of two-photon imaging. For fully automated counting of microglia/monocytes, scans were converted into 3D objects. The animation was created using Imaris.

Bar graph representations of Tables 2A–D.

Central nervous system (CNS) injury has been observed to lead to microglia activation and monocytes infiltration at the lesion site. Ex vivo diffusion magnetic resonance imaging (diffusion MRI or DWI) allows detailed examination of CNS tissues, and recent advances in clearing procedures allow detailed imaging of fluorescent-labeled cells at high re...

Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS) under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that u...

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...