Angela Ruban

Background: Glutamatergic dysfunction has been implicated in schizophrenia. Peripheral metabolic enzymes, including glutamate-oxaloacetate transaminase (GOT/AST) and glutamate-pyruvate transaminase (GPT/ALT), regulate systemic glutamate homeostasis and may serve as accessible biomarkers. This study examined the association between circulating liver transaminase levels and psychotic symptom severity in schizophrenia.Methods: A retrospective observational study was conducted using electronic medical records from patients with schizophrenia (N = 218), yielding 436 observations across ambulatory and hospitalization visits. Symptom severity was assessed using retrospectively assigned SCH-CGI scores and dichotomized into low versus high severity. Predictors included GPT and GOT log-transformed Z-scores, the log-transformed GOT/GPT ratio, age, and sex. Machine learning models (logistic regression, RBF-SVM, and gradient boosting) were applied using group-aware data splitting, and performance was evaluated using ROC-AUC and PR-AUC.Results: Biochemical predictors demonstrated moderate but consistent ability to predict symptom severity among paired hospitalization and ambulatory states patients with schizophrenia. Logistic regression including GPT and GOT log-Z scores achieved the highest performance (ROC-AUC = 0.74; PR-AUC = 0.79), outperforming more complex models. The GOT/GPT ratio did not add predictive value.Conclusions: GOT and GPT were associated with psychotic symptom severity, supporting a potential role for peripheral glutamate metabolism in psychosis. Although predictive performance was modest, these findings highlight the relevance of accessible metabolic markers within multimodal biomarker frameworks and warrant validation in larger prospective studies.

Spinal cord injury (SCI) triggers a rapid and sustained cascade of secondary damage, with glutamate (Glu) excitotoxicity recognized as a central mechanism driving neuronal death and functional decline. Despite extensive research, no effective therapy targeting excitotoxicity, and no neuroprotective treatment in general, is currently available. This highlights the urgent need for novel and effective therapeutic strategies for managing SCI. We developed a combined blood-glutamate scavenging (cBGS) therapeutic platform comprising two recombinant enzymes (rGOT1 and rGPT1), their respective co-substrates (oxaloacetate and pyruvate), and the cofactor pyridoxal phosphate (PLP). The efficacy of cBGS was evaluated in mouse and rat models of moderate-to-severe spinal cord compression and contusion injury. Glutamate concentrations were quantified in blood and cerebrospinal fluid (CSF), while histological and functional outcomes were assessed from 1 day to 7 weeks post-injury to determine neuroprotective efficacy. Systemic cBGS administration significantly reduced Glu concentrations in both blood and CSF, leading to a marked reduction in apoptosis, neuroinflammation, demyelination, and glial scarring, while promoting neuronal and axonal survival. Treated animals demonstrated substantial locomotor recovery, up to 80% improvement in performance. Notably, cBGS remained effective when administered up to eight hours post-injury, indicating a clinically relevant therapeutic window and excellent safety profile. Core findings were independently validated in a rat severe compression model performed by an external Contract Research Organization (CRO). The cBGS platform represents a first-in-class systemic neuroprotective therapy that effectively mitigates glutamate excitotoxicity and secondary injury following SCI. Its robust efficacy, wide therapeutic window, and favorable safety profile support its strong potential for clinical translation in acute SCI and other excitotoxicity-driven neurotrauma conditions, where no effective treatments currently exist.

Background: Cumulative research data indicate that migraine is characterized by a glutamatergic imbalance, particularly an excessive glutamatergic signal. Increases in glutamate levels in the brain and plasma of migraine patients have been reported, but less is known about the association between liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT) that regulate blood glutamate levels and migraine. Objectives: We evaluated associations between AST, ALT, and GGT levels across the quartiles and a history of probable/defined migraine in the Atherosclerosis Risk in Communities Study cohort. Design: We included 11,718 participants with measured liver enzyme levels and self-reported data on migraine with and without aura. Multiple logistic regression models were used to assess associations of sex-specific quartiles of liver enzymes with probable/definite migraine. Results: A total of 1626 probable/definite migraine events were reported in 1993–1995. After adjustment for age, race-center, and sex, higher levels of AST, ALT, and GGT were associated with a lower prevalence of migraine. The adjusted odds ratios (95% CIs) for migraine for Q1 versus Q4 levels of AST, ALT, and GGT were 1.24 (1.06–1.45), 1.17 (1.00–1.37) and 1.21 (1.03–1.41), respectively. Analysis by yes/no aura showed higher odds of migraine without aura for lower (Q1) compared with higher (Q4) levels of ALT (adjusted OR 1.38, 95% CI 1.05–1.82), while no significant association was observed between enzyme levels and prevalence of migraine with aura. Conclusion: Our findings suggest that higher AST, ALT, and GGT levels are associated with a lower prevalence of migraine. Although the exact mechanisms linking lower blood levels of AST, ALT, and GGT to migraines remain unclear, their association may be explained by inefficient plasma glutamate regulation, which could play a role in migraine pathology. This finding is important for patients as it sheds light on potential metabolic contributions to migraines, supporting the hypothesis that factors beyond traditional neurovascular theories are involved.

Previous investigations have demonstrated the therapeutic advantages of extremely low-frequency electromagnetic fields (ELF-EMFs) in mitigating inflammation and influencing biological processes. We aimed to shed light on the effects of ELF-EMF on recovery rate following high-intensity exercise. Nine male athletes (26.7 ± 6.0 years; 69.6 ± 7.7 kg, VO₂peak 57.3 ± 6.8 mL/kg/min) completed five visits in a double-blinded crossover design, performing two consecutive testing days, following a ventilatory thresholds assessment. Following 62 min of high-intensity cycling, participants lay on an ELF-EMF mattress under active (A) and non-active (NA) conditions, immediately post protocol and during the night. Physical performance and blood markers were assessed at baseline and at 60 min (60 P) and 24 h (24 H) post-protocol. The A-condition demonstrated a notable reduction in interleukin-10 (IL-10) concentrations (mean difference = −88%, p = 0.032) and maximal isometric strength of the quadriceps muscles (mean difference = ~8%, p = 0.045) compared to the NA-condition between 60 P and 24 H. In a sensitivity analysis, the A-condition revealed that younger athletes who possessed lower fat mass experienced attenuated inflammation and biochemical responses and improved physical performance. In conclusion, ELF-EMF showed no significant overall effects on performance and inflammation after intense cycling among athletes. Post-hoc analysis revealed modest benefits of ELF-MLF, suggesting a context-dependent impact. Further research with a larger sample size and multiple sessions is needed to confirm the recovery potential of ELF-EMF.

Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate–oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, shortly after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. SAH participants' clinical and neurological status were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH. Furthermore, a logistic regression analysis was carried out to evaluate the ability of GOT1 and glutamate levels to predict neurological outcomes. Our results demonstrated consistently elevated serum and CSF glutamate levels after SAH. Furthermore, serum glutamate level was significantly higher in patients with cerebral ischemia and poor neurological outcome. CSF GOT1 was significantly higher in patients with uncontrolled intracranial hypertension and cerebral ischemia post-SAH, and independently predicted poor neurological outcomes.

Early brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the main causes of poor outcome. The primary injury induces a cascade of events, including increased intracranial pressure (ICP), cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, aspartate, and glutamate-associated enzymes such as glutamate-oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, during the first weeks after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. The clinical and neurological status of SAH participants were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH.Our results demonstrated that serum and CSF glutamate levels were consistently elevated after SAH. Furthermore, high serum glutamate levels displayed a positive correlation with the worst neurological status at admission, and with the cerebral ischemia and poor neurological outcome. CSF GOT1 was elevated in SAH participants and positively correlated with intracranial hypertension, with cerebral ischemia and poor neurological outcome post-SAH.

The COVID-19 infection has generated not only a risk of morbidity and mortality but also resulted in an enormous psychological impact on healthcare providers and the general public. This study aimed to evaluate the prevalence of anxiety and identify the role of protective factors. A two-part cross-sectional study was conducted, by means of an online questionnaire. Part 1 investigated 562 registered nurses, nursing students, and the general public. Participants were assessed for anxiety symptoms with the State-Trait-Anxiety Inventory. A one-way ANCOVA analysis revealed that nurses had the highest level of anxiety compared to the general public and students, with 26% of them reporting severe anxiety. To identify how anxiety can be mitigated, the Part 2 study was focused on registered nurses from Part 1. Multiple regression revealed that a higher level of science-based knowledge of COVID-19 and professional experience were associated with a lower level of anxiety among nurses. The findings suggest that nurses are a vulnerable population prone to anxiety symptoms resulting from the COVID-19 pandemic. Having a deeper science-based understanding of COVID-19 may protect nurses from anxiety. This study underlines the importance of deep evidence-based knowledge for health providers, which may be generalized to a possible future emergency disaster.

Cell therapy using induced pluripotent stem cell‐derived neurons is considered a promising approach to regenerate the injured spinal cord (SC). However, the scar formed at the chronic phase is not a permissive microenvironment for cell or biomaterial engraftment or for tissue assembly. Engineering of a functional human neuronal network is now reported by mimicking the embryonic development of the SC in a 3D dynamic biomaterial‐based microenvironment. Throughout the in vitro cultivation stage, the system's components have a synergistic effect, providing appropriate cues for SC neurogenesis. While the initial biomaterial supported efficient cell differentiation in 3D, the cells remodeled it to provide an inductive microenvironment for the assembly of functional SC implants. The engineered tissues are characterized for morphology and function, and their therapeutic potential is investigated, revealing improved structural and functional outcomes after acute and chronic SC injuries. Such technology is envisioned to be translated to the clinic to rewire human injured SC.

Background: Spinal cord injury (SCI) pathology includes both primary and secondary events. The primary injury includes the original traumatic event, and the secondary injury, beginning immediately after the initial injury, involves progressive neuroinflammation, neuronal excitotoxicity, gliosis, and degeneration. Currently, there is no effective neuroprotective treatment for SCI. However, an accumulating body of data suggests that PELF-EMF has beneficial therapeutic effects on neurotrauma. The purpose of this study was to test the efficacy of the PELF-EMF SEQEX device using a compression SCI mouse model. Methods: C57BL/6 mice were exposed to PELF-EMF for 4 h on a daily basis for two months, beginning 2 h after a mild-moderate compression SCI. Results: The PELF-EMF treatment significantly diminished inflammatory cell infiltration and astrocyte activation by reducing Iba1, F4/80, CD68+ cells, and GAFP at the lesion borders, and increased pro-survival signaling, such as BDNF, on the neuronal cells. Moreover, the treatment exhibited a neuroprotective effect by reducing the demyelination of the axons of the white matter at the lesion’s center. Conclusions: Treatment with SEQEX demonstrated significant anti-inflammatory and neuroprotective effects. Considering our results, this safe and effective rehabilitative device, already available on the market, may provide a major therapeutic asset in the treatment of SCI.

Autism spectrum disorder (ASD) is a neurodevelopmental disease with a wide spectrum of manifestation. The core symptoms of ASD are persistent deficits in social communication, and restricted and repetitive patterns of behavior, interests, or activities. These are often accompanied by intellectual disabilities. At present, there is no designated effective treatment for the core symptoms and co-morbidities of ASD. Recently, interest is rising in medical cannabis as a treatment for ASD, with promising clinical data. However, there is a notable absence of basic pre-clinical research in this field. In this study, we investigate the behavioral and biochemical effects of long-term oral treatment with CBD-enriched medical cannabis oil in a human mutation-basedShank3mouse model of ASD. Our findings show that this treatment alleviates anxiety and decreases repetitive grooming behavior by over 70% in treated mutant mice compared to non-treated mutant mice. Furthermore, we were able to uncover the involvement of CB1 receptor (CB1R) signaling in the Avidekel oil mechanism, alongside a mitigation of cerebrospinal fluid (CSF) glutamate concentrations. Subsequently, RNA sequencing (RNA seq) of cerebellar brain samples revealed changes in mRNA expression of several neurotransmission-related genes post-treatment. Finally, our results question the relevancy of CBD enrichment of medical cannabis for treating the core symptoms of ASD, and emphasize the importance of the THC component for alleviating deficits in repetitive and social behaviors in ASD.