Biology subjects

Georges, B.

Publications and source records attributed to Georges, B..

6 recordsLinked to original sources

bioRxiv2026

CB2 activation during epileptogenesis recruits immunomodulatory monocytes and mitigates cognitive, affective and seizure outcomes

Temporal lobe epilepsy (TLE) is frequently associated with severe cognitive impairment and psychiatric comorbidities that are highly disabling and not targeted by anti-seizure medications, highlighting the need for therapies that target epileptogenesis rather than merely suppress seizures. Despite strong evidence implicating neuroinflammation in this process, anti-inflammatory approaches have not yielded such therapies yet. Infiltrating peripheral monocytes are widely viewed as detrimental amplifiers of post-status epilepticus (SE) inflammation, although emerging data suggest context-dependent protective roles. The cannabinoid receptor type 2 (CB2), highly expressed in myeloid cells, represents a potential immunomodulatory target linking leukocyte recruitment and inflammatory polarization. Using a juvenile rat model of TLE, we characterized hippocampal neuroinflammation and CB2 expression during epileptogenesis and evaluated the effects of transient CB2 activation with the selective agonist GP1a. SE induced a rapid but transient inflammatory response and robust recruitment of peripheral monocytes that persisted as anti-inflammatory monocyte-derived macrophages. CB2 activation did not suppress early cytokine induction but selectively enhanced recruitment of anti-inflammatory monocytes and modestly increased anti-inflammatory signaling. Importantly, transient CB2 stimulation preserved synaptic plasticity, improved cognitive performance, reduced anxiety-like behavior, and delayed seizure onset. These findings identify CB2-dependent modulation of peripheral myeloid cells as a potential disease-modifying axis in TLE.

neuroscience↗

bioRxiv2025

Brain Infiltrated Monocyte-Macrophages in a rat model of Temporal Lobe Epilepsy: Revisiting the Pro-Inflammatory Paradigm

Neuroinflammation is central to temporal lobe epilepsy, yet the specific role of myeloid cells remains unclear. In status epilepticus (SE) models, circulating monocytes have been reported to infiltrate the brain, though distinguishing them from microglia remains challenging. Using a rat model, we traced infiltrating monocytes post-SE, to investigate their persistence, phenotypic evolution during epileptogenesis and contribution to neuroinflammation. By tracking phagocyted fluorescent nanoparticles and using CD68 immunohistochemistry, we confirmed that monocytes entered the brain in significant numbers 24 hours post-SE, after the inflammatory peak occurred (7h post-SE). Tracked up to 7 weeks, these cells adopted a microglia-like phenotype, contributed to the microglial scar and sustained low-grade inflammation during the chronic phase of epilepsy solely through their presence, as their expression of pro-inflammatory markers resembled that of non-activated microglia. Importantly, monocytes initially and transiently supported an anti-inflammatory response providing a unique opportunity to modulate neuroinflammation and potentially disrupt epilepsy progression, opening new avenues for therapeutic interventions.

neuroscience↗

bioRxiv2023

Cannabinoid receptor type 2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions

Since its detection in the brain, the cannabinoid receptor type 2 (CB2) has been deemed a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of CB2 expression is currently lacking. Using magnetic cell sorting, calibrated reverse transcription-quantitative PCR, and single-nucleus RNA-seq, we revealed the low level of CB2 expression in all brain regions examined, mainly by a few microglial cells and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation to simulate non-sterile neuroinflammatory conditions, we demonstrated that the inflammatory response was associated with a transient reduction in CB2 mRNA levels in the brain tissue, particularly in microglia. This result, confirmed in the BV2 microglial cells, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, which models sterile inflammatory conditions. Thus, discrete brain CB2 expression may be upregulated or downregulated depending on the inflammatory context.

neuroscience↗

bioRxiv2021

Respiratory dysfunctions in two rodent models of chronic epilepsy and acute seizures and their link with brainstem serotonin system

Patients with drug-resistant epilepsy can experience respiratory alterations notably during seizures. The mechanisms underlying this long-term alteration of respiratory function remain unclear. This study aimed at determining in rats whether epilepsy is associated with alterations of both the respiratory function and brainstem serotonin (5-HT) system. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. 30-50% of epileptic (EPI) rats exhibited sharp decrease of oxygen consumption (SDOC), low metabolic rate of oxygen and slow regular ventilation; these rats were called EPI/SDOC+ rats. These alterations were only detected in rats with chronic epilepsy, independent of behavioral seizures, persisted over the time, and were not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was below that of control and EPI/SDOC-rats. Both EPI/SDOC+ rats and DBA/2 mice presenting with fatal respiratory arrest following an audiogenic-induced seizure, a model of sudden and expected death in epilepsy, had increased transcript levels of tryptophan hydroxylase 2 (p<0.001 for both strains) and 5-HT presynaptic transporter (rats: p=0.003; mice: p=0.001). Thus, our data support that 5-HT alterations are associated with chronic and acute epilepsy-related respiratory dysfunctions.

neuroscience↗

bioRxiv2021

Low grade inflammation in the epileptic hippocampus contrasts with explosive inflammation occurring in the acute phase following status epilepticus in rats: translation to patients with epilepsy

There is still a lack of robust data, acquired identically and reliably from tissues either surgically resected from patients with mesial temporal lobe epilepsy (mTLE) or collected in animal models, to answer the question of whether the degree of inflammation of the hippocampus differs between mTLE patients, and between epilepsy and epileptogenesis. Here, using highly calibrated RTqPCR, we show that neuroinflammatory marker expression was highly variable in the hippocampus and the amygdala of mTLE patients. This variability was not associated with gender, age, duration of epilepsy, seizure frequency, and anti-seizure drug treatments. In addition, it did not correlate between the two structures and was reduced when the inflammatory status was averaged between the two structures. We also show that brain tissue not frozen within minutes after resection had significantly decreased housekeeping gene transcript levels, precluding the possibility of using post-mortem tissues to assess physiological baseline transcript levels in the hippocampus. We thus used rat models of mTLE, induced by status epilepticus (SE), that have the advantage of providing access to physiological baseline values. They indisputably indicated that inflammation measured during the chronic phase of epilepsy was much lower than the explosive inflammation occurring after SE, and was only detected when epilepsy was associated with massive neurodegeneration and gliosis. Comparison between the inter-individual variability measured in patients and that established in all epileptic and control rats suggests that some mTLE patients may have very low inflammation in the hippocampus, close to control values. However, the observation of elevated inflammation in the amygdala of some patients indicates that inflammation should be studied not only at the epileptic hippocampus, but also in the associated brain structures in order to have a more integrated view of the degree of inflammation present in brain networks involved in mesial temporal lobe epilepsy.

neuroscience↗

bioRxiv2020

Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

immunology↗