Makram Obeid

The long-term effects of non-convulsive status epilepticus (NCSE) and their mechanisms in the brain remain largely unknown. Such insight is needed to better shape the clinical approach to this condition. Here, we investigated long-term alterations in hippocampal transcriptomic profiles following an episode of limbic NCSE in periadolescent rats. Cortical and hippocampal mRNA expressions were measured 2 months following intrahippocampal kainic acid (NCSE group, n = 3) or saline injections (controls, n = 4). Compared to controls, NCSE-treated rodents exhibited a significant twofold downregulation in 126 genes in the CA1 hippocampal subfield, 11 in the CA2-3 region, and 21 in the dentate/hilar areas. Most of the identified genes are known to play an essential role in learning and hippocampal plasticity. Additional roles include modulation of inflammatory responses. Twenty altered genes are known to contribute to human intellectual and mental disease pathology, and nine out of these are direct causes of cognitive and neurodevelopmental brain disorders. Spatial deconvolution analyses revealed NCSE-related increases in CA2-3 microglia and hilar astrocytes coupled with increases in dentate GABAergic neurons. These long-term region-specific cellular and molecular hippocampal alterations may contribute to both inflammatory states and disturbances in neuronal function. Taken together, these gene expression changes are suggestive of neuroinflammation-driven synaptic dysfunction following NCSE.

Emerging evidence highlights the transformative potential of transcranial focused ultrasound in enhancing brain function and repair. Low-intensity focused ultrasound (LIFUS) enables precise, non-invasive modulation of neuronal activity, promoting cellular repair and brain plasticity. By targeting specific brain regions, LIFUS facilitates the release of neurotrophic factors, strengthens synaptic connectivity, and modulates molecular and cellular pathways essential for neural recovery. These mechanisms collectively support neuronal proliferation, differentiation, and functional integration, leading to cognitive improvements and neuroprotection without causing thermal damage. This review provides a comprehensive overview of LIFUS's effects on brain function, emphasizing its role in neuromodulation, cellular adaptation, and long-term viability for treating brain injuries and neurodegenerative diseases. The discussion covers optimized ultrasound parameters, efficacy in cellular and behavioral models, and its therapeutic potential for brain repair and functional recovery. By extending its scope beyond isolated mechanisms, LIFUS emerges as a versatile neuromodulation tool with significant clinical promise for enhancing brain resilience and cognitive outcomes.

Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10–50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable. A 5-year retrospective review was conducted at the American University of Beirut Medical Center to identify children who underwent whole exome sequencing (WES) or whole genome sequencing (WGS). Data on patient demographics, neurodevelopment, seizures, and treatments were collected. Forty-nine children underwent NGS with an overall diagnostic rate of 68.9% (27/38 for WES, and 4/7 for WGS). Most children (42) had neurodevelopmental delays with (18) or without (24) refractory epilepsy, and only three had refractory epilepsy without delays. The diagnostic yield was 77.8% in consanguineous families (18), and 61.5% in non-consanguineous families (26); consanguinity information was not available for one family. Genetic test results led to anti-seizure medication optimization or dietary therapies in six children, with subsequent improvements in seizure control and neurodevelopmental trajectories. Not only is the diagnostic rate of NGS high in children with unexplained epilepsy and neurodevelopmental delays, but also genetic testing in this population may often lead to potentially life-altering interventions.

Organic electrochemical transistors (OECTs) have emerged as powerful tools for biosignal amplification, including electrocorticography (ECoG). However, their widespread application has been limited by the complexities associated with existing fabrication techniques, restricting accessibility and scalability. Here, we introduce a novel all-planar, all-printed high-performance OECT device that significantly enhances the accuracy and sensitivity of ECoG recordings. Achieved through an innovative three-step drop-on-demand inkjet printing process on flexible substrates, our device offers a rapid response time of 0.5 ms, a compact channel area of 1950 μm², and is characterized by a transconductance of 11 mS. This process not only simplifies integration but also reduces costs. Our optimized in-plane gate voltage control facilitates operation at peak transconductance, which elevates the signal-to-noise ratio (SNR) by up to 133%. In vivo evaluations in a rat model of seizure demonstrate the device's performance in recording distinct electrographic phases, surpassing the capabilities of PEDOT:PSS-coated gold-based ultralow impedance passive electrodes, achieving a high SNR of 48 db. Our results underscore the potential of Inkjet-printed OECTs in advancing the accessibility and accuracy of diagnostic tools that could enhance patient care by facilitating timely detection of neurological conditions.

Toxoplasma gondii is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. Toxoplasma gondii (T. gondii) transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening. Behavioral and neurological complications have been associated with CT. Furthermore, an effective treatment targeting CT is still lacking. We previously reported the efficacy of imiquimod against CT. Here, we demonstrate the molecular effects of imiquimod or imiquimod followed by the clinically used combination of sulfadiazine and pyrimethamine (SDZ + PYR) on CT-associated behavior in a rat model. Imiquimod decreased the number of cysts in the brains of chronically infected rats due to an induced reactivation of bradyzoites into tachyzoites. Importantly, this decrease was more pronounced in rats treated with imiquimod followed by SDZ + PYR. Rats chronically infected with T. gondii exhibited an anxiety-like behavior. Notably, treatment with imiquimod reversed this behavior aberrancy, with even a more pronounced effect with imiquimod followed by SDZ/PYR. Similarly, rats chronically infected with T. gondii exhibited learning deficits, and imiquimod alone or followed by SDZ/PYR reversed this behavior. Our results enhance our knowledge of the implications of CT on behavioral aberrancies and highlight the potency of imiquimod followed by SDZ + PYR on these CT-associated complications.

New onset refractory status epilepticus (NORSE) is an etiologically heterogeneous condition that is associated with high morbidity and mortality. NORSE is often refractory to medical management prom