Speakers - NWC 2024

Abstract

Extracellular vesicles (EVs), characterized by their diverse biological functions, have emerged as crucial elements in medical diagnostics and therapeutics. These cell-derived vesicles encapsulate a range of molecular constituents reflective of their cells of origin, offering a window into various physiological and pathological processes. Among these, astrocyte-derived extracellular vesicles, termed neuro-EVs, have attracted significant attention for their potential role in neurology.

In neurological disorders like traumatic brain injury (TBI) and neurodegenerative diseases, elevated concentrations of neuro-EVs have been detected, marking their significance in brain-related pathologies. These vesicles, carrying markers of their parent astrocytes, are released during cell activation or apoptosis and are vital in maintaining the blood-brain barrier (BBB). Our initial encounter with neuro-EVs in TBI patients led us to hypothesize their relevance in stress-induced exhaustion disorder (SED), a condition with symptoms and cognitive dysfunctions akin to minor TBI. These parallels suggested a potential neurological component in SED, distinct from major depressive disorder (MDD), where such profound cognitive dysfunctions are less pronounced.

Prolonged, unrelieved stress, characterizing SED, leads to chronic exhaustion, emotional instability, impaired sleep, and cognitive issues, closely mirroring neurocognitive symptoms observed in minor TBI. Interestingly, research has demonstrated structural changes in critical brain regions like the medial prefrontal cortex, hippocampus, and amygdala in SED patients, further strengthening the neurobiological link. Given these similarities, the hypothesis was that SED patients would exhibit increased neuro-EV concentrations, akin to TBI patients.

Subsequent investigations confirmed this hypothesis, revealing higher concentrations of astrocyte-derived EVs in SED patients. This finding was pivotal in establishing SED as a condition with a significant neurological component, further distinguished from MDD by the unique profile of neuro-EVs.

To validate the broad applicability of neuro-EVs as biomarkers, we extended our research to COVID-19 patients. Observations of longitudinal changes in neuro-EV profiles in these patients suggested a potential interaction between viral pathogenesis, systemic inflammation, and neurological impact.

In conclusion, our findings underscore neuro-EVs' potential as novel and non-invasive biomarkers for neurological research. Their ability to reflect neural disturbances in diverse conditions, from TBI and SED to infectious diseases like COVID-19, supports their utility in advancing diagnostic modalities, understanding disease progression, and potentially guiding therapeutic interventions in neurology and related fields. Detecting neuro-EVs through simple blood tests offers a promising avenue for elucidating pathophysiological mechanisms and managing various neurological conditions.