Biology subjects

Plautz, E. J.

Publications and source records attributed to Plautz, E. J..

5 recordsLinked to original sources

bioRxiv2026

Distinct spatiotemporal immunometabolic remodeling following acute traumatic brain injury

Traumatic brain injury induces profound metabolic reprogramming across neurons, astrocytes, and microglia, yet the spatiotemporal organization of these metabolic responses remains poorly understood. Because pyruvate is uniquely positioned in cerebral metabolism by connecting glycolysis, lactate metabolism, and the tricarboxylic acid cycle, we combined matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging with in vivo administration of isotopically labeled pyruvate and immunohistochemistry to characterize cell-type-wise metabolic remodeling in a controlled cortical impact rat model during the acute and subacute phases of injury. TBI induced distinct spatiotemporal immunometabolic remodeling across neuroglial compartments. Microglia- and macrophage-enriched regions exhibited selective accumulation of citrate, succinate, and itaconate, consistent with inflammatory metabolic rewiring. In contrast, astrocyte enriched regions showed increased glutamine and malate abundance, indicative of altered neuron-astrocyte metabolic coupling such as remodeling of the glutamate-glutamine cycle and enhanced anaplerotic metabolism. These metabolic signatures evolved with distinct regional and temporal distributions, identifying compartmentalized metabolic responses. Notably, labeled isotopologues of selected metabolites, including glutamate and citrate derived from administered pyruvate, changed before the corresponding metabolite pools. Together, these findings describe the spatiotemporal landscape of immunometabolic remodeling following acute TBI, uncover metabolically distinct microglial/macrophage and astrocytic responses during secondary brain injury, and identify candidate metabolic pathways for therapeutic intervention and metabolic imaging.

biochemistry↗

bioRxiv2026

Peripheral B cell populations tune spontaneous neuronal activity in the uninjured hippocampus after stroke

B cells infiltrate the contralesional hippocampus following stroke, but whether lymphocytes modulate post-stroke plasticity and neuronal network function remains unknown. To identify immune cell mechanism(s) supporting remote plasticity, we examined the impact of B cell depletion on synaptic and neuronal activity in the hippocampal circuit following stroke. Basal synaptic transmission in the contralesional dentate gyrus (DG) following a stroke in adult male mice was decreased with B cell depletion. Expanding our studies to encompass the CA1 and DG regions of the hippocampal circuit in male and female mice of different ages, we utilized synapsin-Cre/GCaMP6s mice to visualize spontaneous calcium activity during a 3-week B cell depletion with and without prior stroke. Systemic B cell depletion in the absence of injury altered neuronal activity in the DG, suggesting a novel neuromodulatory role for circulating immune cells. Stroke increased Ca2+ transient amplitudes in the contralesional DG and CA1, with B cell depletion again reducing DG amplitudes while increasing the frequency of Ca2+ transients. Robust linear regression revealed significant main effects and higher-order interactions (depletionxsexxagexinjury), including increased Ca2+ transient amplitudes in older post-stroke mice lowered by systemic B cell depletion, though overall the DG appears more sensitive to modulation versus CA1. These results suggest that circulating B cells can tune hippocampal network activity dependent on age, sex, and the presence of brain injury. The selective vulnerability of the DG to depletion-age-injury interactions opens an avenue for future studies on region-specific neuroimmune crosstalk during post-stroke cognitive recovery. Presubmission inquiry for NeuronWe uncover crucial insights on the capacity of circulating B cells to directly modulate hippocampal network activity, showing that B cells are not just passive players, but active neuromodulators whose effects are dependent on sex, age, and stroke injury status. In fact, B cells are central players to functional recovery whose evolving role shifts over time, from acutely beneficial and neurotrophic to chronically maladaptive, depending on timing, context, and responding B cell subset. Our study demonstrates a mechanistic link between systemic immune modulation and neuronal calcium activity. This integrative perspective aligns with Neurons mission to publish studies that link cellular processes to systems-level functions. These novel findings also add to a more unified model of neuro-immune interactions that highlights how immunotherapies could be harnessed to improve neuronal function during stroke and aging, with several FDA-approved immunotherapeutics available to modulate systemic adaptive immune responses.

neuroscience↗

bioRxiv2026

Shared Transcriptomic Signatures in Perilesional and Contralesional Cortex

Stroke induces a transient period of heightened plasticity during which functional recovery is most pronounced. Work in rodent models of stroke has identified key mechanisms in both the ipsilesional and contralesional cortex that contribute to functional and structural post-stroke plasticity. To date, most gene expression studies have focused on the infarct core and the immediately surrounding tissue, peri-lesional cortex (PLC). We sought to understand whether the contralesional cortex (CLC), a region that shows robust structural and molecular remodeling despite its distance from the lesion, mounts a distinct transcriptional response to stroke. Direct comparisons of molecular pathways governing these regions, particularly across sexes, are limited. To address this gap, we performed bulk RNA sequencing of the PLC and CLC at 7 days post-stroke, a critical time point for initiating repair, in male and female mice. Our results indicate that despite distinct positions from the lesion, both regions share a robust upregulation of inflammatory signaling, with Gene Ontology enrichment indicating activation of cytokine signaling, leukocyte activation, and gliogenesis pathways. Further analysis of this shared gene expression signature revealed reactive microglia signaling as the dominant pathway. Surprisingly, the CLC did not show a distinct transcriptional response. These findings were consistent across males and females, which also showed similar CLC-derived corticospinal tract axonal sprouting at 6 weeks post-stroke. Together, these findings support a shared microglia-centered neuroinflammatory transcriptional response in the PLC and CLC and suggest that microglial reactivity is a key early process for post-stroke cortical plasticity in both male and female mice.

neuroscience↗

bioRxiv2025

Uncovering a new player in ischemic stroke: a study of intra-arterial interferon-gamma-producing monocytes in hyperacute stroke

Stroke triggers a rapid and complex immune response that is not yet fully understood, especially within hours after an ischemic infarct. Our previous study in stroke patients revealed a significant increase in interferon- gamma (IFN-{gamma}) immediately (hyperacute) and downstream of the ischemic ictus, within the arterial compartment. The present study investigated the source, inciting factors, and role of IFN-{gamma} in a preclinical murine model. Stroke was produced using transient middle cerebral artery occlusion, and immune cells within the arterial vasculature distal to the occlusion (pre- and post-occlusion) were characterized using flow cytometry. Compared with the control samples, the post-occlusion samples presented an increase in IFN-{gamma}+ and CD69+ cells, whereas no significant increase was detected in IL17+, IL4+, and CD25+ cells. Further analysis of the IFN-{gamma}+ population revealed two novel attributes. First, interrogation of the identity of these IFN-{gamma}+ cells revealed that the increase in IFN-{gamma} production was largely driven by CD14+ cells in the post- occlusion sample, with negligible contributions from other canonical IFN-{gamma}-producing cells (CD4, CD8). Second, the IFN-{gamma}+ cells exhibited two distinct clusters, an IFN-{gamma}low and an IFN-{gamma}hi population. Further analysis revealed that the IFN-{gamma} low population was largely composed of CD14+ cells, whereas the IFN-{gamma}hi population was dominated by CD4+ T-cells. To explore the conditions driving IFN-{gamma} production, an in vitro ischemia model involving oxygen-glucose deprivation (OGD) was employed. Co-culturing of naive splenocytes with OGD-treated CNS cells and OGD-derived supernatant resulted in a significant increase in IFN-{gamma}+CD14+ cells, as compared to normoxic controls, an effect that coincided with marked loss of DAPI+ and NeuN+DAPI+ cells in mixed cortical (neuronal and glial) cultures. In summary, this study identified intra-arterial CD14+ monocytes as novel early sources of IFN-{gamma} in the hyperacute phase of stroke, a role traditionally attributed to adaptive immune cells. Using in vivo and in vitro ischemia models, the findings reveal that injury-associated signals from CNS cells are sufficient to directly induce IFN-{gamma} production in CD14+ cells, redefining early stroke immunopathology and uncovering a potential target for timely immunomodulation.

immunology↗

bioRxiv2024

SpinalTRAQ: A novel volumetric cervical spinal cord atlas identifies the corticospinal tract synaptic projectome in healthy and post-stroke mice

Abstract/SummaryDescending corticospinal tract (CST) connections to the neurons of the cervical spinal cord are vital for performance of forelimb-specific fine motor skills. In rodents, CST axons are almost entirely crossed at the level of the medullary decussation. While specific contralateral axon projections have been well-characterized using anatomic and molecular approaches, the field currently lacks a cohesive imaging modality allowing rapid quantitative assessment of the entire, bilateral cervical cord projectome at the level of individual laminae and cervical levels. This is potentially important as the CST is known to undergo marked structural remodeling in development, injury, and disease. We developed SpinalTRAQ (Spinal cord Tomographic Registration and Automated Quantification), a novel volumetric cervical spinal cord atlas and machine learning-driven microscopy acquisition and analysis pipeline that uses serial two-photon tomography-images to generate unbiased, region-specific quantification of the fluorescent pixels of anterograde AAV-labeled CST pre-synaptic terminals. In adult mice, the CST synaptic projectome densely innervates the contralateral hemicord, particularly in laminae 5 and 7, with sparse, monosynaptic input to motoneurons in lamina 9. Motor pools supplying axial musculature in the upper cervical cord are bilaterally innervated. The remainder of the ipsilateral cord has sparse labeling in a distinct distribution compared to the contralateral side. Following a focal stroke of the motor cortex, there is a complete loss of descending corticospinal axons from the injured side. Consistent with prior reports of axon collateralization, the CST spinal projectome increases at four weeks post-stroke and continues to elevate by six weeks post stroke. At six weeks post-stroke, we observed striking synapse formation in the denervated hemicord from the uninjured CST in a homotopic distribution. Additionally, CST synaptic reinnervation increases in the denervated lamina 9 in nearly all motoneuron pools, exhibiting novel patterns of connectivity. Detailed level- and lamina-specific quantification of the bilateral cervical spinal cord synaptic projectome reveals previously undescribed patterns of CST connectivity in health and injury-related plasticity.

neuroscience↗