Biology subjects

Vaudry, D.

Publications and source records attributed to Vaudry, D..

6 recordsLinked to original sources

bioRxiv2025

Innovative 3D-image analysis of cerebellar vascularization highlights angiogenic gene dysregulations in a murine model of apnea of prematurity

Apnea of prematurity (AOP) affects 50% of preterm infants causing intermittent hypoxia (IH), which can lead to long-term neurodevelopmental deficits. Cerebellar abnormalities have been observed in AOP but the relationship between vascular alterations and neural development remains unclear. This study investigates how IH affects cerebellar angiogenesis using a murine model of AOP. We developed an innovative 3D imaging workflow combining IMARIS and VesselVio software to quantitatively analyze cerebellar vascularization at different postnatal stages (P4, P8, P12, P21, and P70). We correlate these results with a transcriptomic analysis of 23 angiogenesis-related genes in the same stages to uncover the associated molecular pathways. We found that IH induced significant vascular changes, particularly at P4, with a global increase in vascular-network dimensions. By P8, the vascular network normalized, but genes were downregulated in all pathways studied. After P12, at the end of the IH protocol, transcriptional regulations vary but persist long-term. Moreover, differential analysis showed distinct effects on superficial versus deep vascular networks, allowing for a more precise understanding of remodeling patterns throughout development. Overall, transcriptomic changes were associated with morphological alterations in a time-dependent manner, suggesting a multiphasic IH response through development with lasting effects. Key regulations included VEGF, angiopoietin, and matrix metalloprotease signaling. These findings demonstrate that IH disrupts cerebellar angiogenesis in parallel with neurogenesis, potentially contributing to the neurodevelopmental deficits observed in AOP. Thus, the interconnected nature of angio- and neurogenesis during cerebellar development makes it crucial to take vascular aspects into account in therapeutic approaches to neurodevelopmental disorders. HighlightsO_LINovel 3D imaging workflow reveals cerebellar vascular changes in apnea of prematurity mouse model C_LIO_LIIntermittent hypoxia induces early hypervascularization at P4 followed by later adaptation C_LIO_LISuperficial and deep vascular networks show distinct responses to intermittent hypoxia C_LIO_LIVascularization-related genes are affected during cerebellar development C_LIO_LIAlterations in angiogenesis go together with neurodevelopmental defects C_LI

neuroscience↗

bioRxiv2025

Anti-PD-1/PD-L1 Therapy Triggers Cognitive Deficits and Anxiety-Like Behaviors Through Tumor-Initiated Neuroinflammatory Niches in Male Mice

Checkpoint inhibitors are promising immunotherapy to treat cancer patients, but their cognitive impact has not been evaluated despite several neurological adverse events. We studied the impact of immune desert or inflamed cancers when combined with immune checkpoint inhibitors (ICI) anti-PD-1/anti-PD-L1 on mouse behaviors and brain immune cells infiltration/homeostasis, and neuroinflammation in male mice. We showed that systemic inflammation, brain-barriers permeability accompanying meningeal infiltration of peripheral macrophages and neuroinflammation as well as deficits in cognition or emotional reactivity, depending on immuno-inflammatory or immune-desert cancer type. Combined with cancers, anti-PD-1 and PD-L1 treatments exacerbated the decline in executive functions and hippocampal vascular inflammation. PD-L1 specifically relayed the infiltration of the T{gamma}{delta} lymphocytes subpopulation in choroid plexus and leptomeninges implicated, whose systemic neutralization counteracted anti-PDL1-induced cognitive deficits and anxiety in mice bearing immune-inflamed cancer. Our findings highlight new systemic biomarkers of cold or hot cancer, treated with anti-PD-1/anti-PDL-1, and associated with cognitive and emotional alterations in mice; guiding ways of intervention to secure the cancer curation and improve patients quality of life under ICI treatment. Competing Interest StatementThe authors have declared no competing interest. One Sentence SummaryImpact of cancer and checkpoint inhibitors on cognitive functions

cancer biology↗

bioRxiv2025

Activation of Endogenous Spinal Cord Stem Cell Mediates Recovery Induced by Olfactory Ensheathing Cell Transplantation Following Spinal Cord Injury

Spinal cord injury (SCI) leads to irreversible motor and sensory deficits and currently has no curative treatment. Among the various therapeutic strategies explored, cell transplantation-- using either stem or differentiated cells--has been extensively studied. One of the most promising approaches involves the use of olfactory ensheathing cells (OECs), which have demonstrated unique potential to promote functional recovery and tissue repair following SCI. However, the mechanisms underlying these effects remain poorly understood. In this study, we investigated how OEC transplantation modulates endogenous spinal stem cells, with a particular focus on ependymal cells. Using inducible transgenic mouse lines and fate-mapping approaches, we show that OEC transplantation significantly enhances ependymal cell proliferation and self-renewal both in vivo and in vitro. Moreover, OECs promote astrocytic differentiation of ependymal progeny, which express low levels of inhibitory molecules-- suggesting a supportive role in creating a permissive scar microenvironment. Transcriptomic analyses further revealed that OEC transplantation downregulates genes associated with axonal growth inhibition, thereby contributing to improved neuronal survival. Finally, by using a unique transgenic mouse model in which ependymal cell proliferation is genetically blocked, we demonstrate that the beneficial effects of OEC transplantation depend on ependymal cell activation. Together, these findings establish ependymal cells as essential mediators of the regenerative response induced by OECs. They also highlight a therapeutic strategy based on activating and modulating endogenous stem cells via the transient presence of non-integrating transplanted glial cells. This work contributes to our understanding of SCI repair and supports the clinical potential of OEC-based cell therapies.

neuroscience↗

bioRxiv2020

Prolonged deficit of gamma oscillations in the peri-infarct cortex of mice after stroke

Days and weeks after an ischemic stroke, the peri-infarct area adjacent to the necrotic tissue exhibits very intense synaptic reorganization aimed at regaining lost functions. In order to enhance functional recovery, it is important to understand the mechanisms supporting neural repair and neuroplasticity in the cortex surrounding the lesion. Brain oscillations of the local field potential (LFP) are rhythmic fluctuations of neuronal excitability aimed at synchronizing neuronal activity to organize information processing and plasticity. Although the oscillatory activity of the brain has been probed after stroke in both animals and humans using electroencephalography (EEG), the latter is ineffective to precisely map the oscillatory changes in the peri-infarct zone where synaptic plasticity potential is high. Here, we worked on the hypothesis that brain oscillatory system is altered in the surviving peri-infarct cortex, which may slow down functional repair and reduce the capacity to recovery. In order to document the relevance of this hypothesis, oscillatory power was measured at various distances from the necrotic core at 7 and 21 days after a permanent cortical ischemia induced in mice. Delta and theta oscillations remained at a normal power in the peri-infarct cortex, in contrast to gamma oscillations that displayed a rapid decrease, the closer we get to the lesion core. A broadband increase of power was also observed in the homotopic contralateral sites. Thus, the proximal peri-infarct cortex could become a target of therapeutic interventions aimed at correcting the oscillatory regimen. These results argue for the usefulness of therapeutic intervention aimed at boosting gamma oscillations in order to improve post-stroke functional recovery.

neuroscience↗

bioRxiv2020

The gliopeptide ODN, a ligand for the benzodiazepine site of GABAA receptors, boosts functional recovery after stroke

Following stroke, the survival of neurons and their ability to re-establish connections is critical to functional recovery. This is strongly influenced by the balance between neuronal excitation and inhibition. In the acute phase of experimental stroke, lethal hyperexcitability can be attenuated by positive allosteric modulation of GABAA receptors (GABAAR). Conversely, in the late phase, negative allosteric modulation of GABAAR can correct the sub-optimal excitability and improves both sensory and motor recovery. Here, we hypothesized that octadecaneuropeptide (ODN), an endogenous allosteric modulator of the GABAAR synthesized by astrocytes, influences the outcome of ischemic brain tissue and subsequent functional recovery. We show that ODN boosts the excitability of cortical neurons, which make it deleterious in the acute phase of stroke. However, if delivered after day 3, ODN is safe and improves motor recovery over the following month in two different paradigms of experimental stroke in mice. Furthermore, we bring evidence that during the sub-acute period after stroke, the repairing cortex can be treated with ODN by means of a single hydrogel deposit into the stroke cavity. SIGNIFICANCE STATEMENTStroke remains a devastating clinical challenge because there is no efficient therapy to either minimize neuronal death with neuroprotective drugs or to enhance spontaneous recovery with neurorepair drugs. Around the brain damage, the peri-infarct cortex can be viewed as a reservoir of plasticity. However, the potential of wiring new circuits in these areas is restrained by a chronic excess of GABAergic inhibition. Here we show that an astrocyte-derived peptide (ODN), can be used as a delayed treatment, to safely correct cortical excitability and facilitate sensorimotor recovery after stroke.

neuroscience↗

bioRxiv2018

Octadecaneuropeptide prevents toxicity induced by 6-hydroxydopamine in cultured rat astrocyte: involvement of the endogenous antioxidant systems and the intrinsic apoptotic pathway

Oxidative stress, associated with various neurodegenerative diseases, induces imbalance in ROS generation, impairs cellular antioxidant defences and finally triggers both neurons and astroglial cell death by apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). We have previously reported that ODN is a potent neuroprotective agent that prevents 6-OHDA-induced apoptotic neuronal death. The purpose of the present study was to investigate the potential glioprotective effect of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Incubation of astrocytes with graded concentrations of ODN (10-14 to 10-8 M) inhibited 6-OHDA-evoked cell death in a concentration- and time-dependent manner. In addition, ODN prevented the decrease of mitochondrial activity and caspase-3 activation induced by 6-OHDA. Toxin-treated cells exhibited high level of ROS associated with a generation of H2O2 and O2{degrees}-and a reduction of both SOD and catalase activities. Co-treatment of astrocytes with low concentrations of ODN dose dependently blocked 6-OHDA-evoked ROS production and inhibition of antioxidant enzymes activities. Taken together, these data demonstrate that ODN is a potent glioprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death. ODN is thus a potential candidate to delay neuronal damages in various pathological conditions involving oxidative neurodegeneration.

cell biology↗