Biology subjects

Arja, R. D.

Publications and source records attributed to Arja, R. D..

4 recordsLinked to original sources

bioRxiv2023

Functional Connectivity, Tissue Microstructure And T2 At 11.1 Tesla Distinguishes Neuroadaptive Differences In Two Contusive Brain Injury Models In Rats

Traumatic brain injuries (TBIs), particularly contusive types, are associated with disruptions in neuronal communication due to focal and diffuse axonal injury, as well as alterations in the neuronal chemical environment. These changes can negatively impact neuronal networks beyond the primary injury site. In this Translational Outcomes Project in NeuroTrauma (TOP-NT) UG3 phase study, we sought to use multimodal neuroimaging biomarker approach to assess functional connectivity and brain tissue microstructure, along with T2 relaxometry, in two experimental rat models of TBI: controlled cortical impact (CCI) and lateral fluid percussive injury (LFPI). Rats underwent imaging using an 11.1 Tesla scanner at 2 and 30 days post-injury. Naive controls were scanned once to establish baseline comparisons for both TBI groups. Imaging modalities included functional magnetic resonance imaging (fMRI), diffusion-weighted imaging (DWI), and multi-echo T2 imaging. fMRI data were analyzed to evaluate functional connectivity across lateral and medial regions of interest (ROIs) in the cortical mantle, hippocampus, and dorsal striatum. DWI scans were used to generate maps of fractional anisotropy (FA) and mean, axial, and radial diffusivities (MD, AD, RD), focusing on cortical and white matter (WM) regions near the injury epicenter. Our findings revealed significantly increased contralateral intra-cortical connectivity at 2 days post-injury in both CCI and LFPI models, localized to similar cortical areas. This increased connectivity persisted at day 30 in the CCI model but not in LFPI. Changes in WM and cortical FA and diffusivities were observed in both models, with WM alterations predominating in CCI and cortical changes being more pronounced in LFPI. These results highlight the utility of multimodal MR imaging for characterizing distinct injury mechanisms in contusive and skull-penetrating TBI models.

neuroscience↗

bioRxiv2023

Sleep Disruption in a Mouse Model of Chronic Traumatic Brain Injury

Chronic sleep/wake disturbances are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong sleep/wake disturbances. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in four months old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. The sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at three months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Furthermore, TBI mice showed extensive brain tissue loss and increased GFAP and IBA1 levels in the hypothalamus and the vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes following TBI early in life.

neuroscience↗

bioRxiv2022

Two subsets of circulating Ly6Clo monocytes distinguished by CD138 (syndecan-1) expression and Nr4a1 dependence in pristane-treated mice

Chronic peritoneal inflammation following pristane injection induces lupus with diffuse alveolar hemorrhage (DAH) and pulmonary capillaritis in C57BL/6 mice. The pathogenesis involves pristane-induced microvascular lung injury. BALB/c mice are resistant to endothelial injury and DAH. Lung disease in C57BL/6 mice is abolished by depleting monocytes/macrophages. The objective of this study was to define the role of myeloid subsets in DAH. Hemorrhage and vasculitis were abolished in Ccr2-/- mice, indicating involvement of bone marrow-derived monocytes/macrophages. Along with Ly6Chi monocytes, we found two subsets of circulating Ly6Clo monocytes: one CD138- and a novel CD138+ subset. Nr4a1-dependent patrolling Ly6Clo monocytes maintain vascular integrity after endothelial injury. Circulating Ly6CloCD138+ monocytes were associated with DAH and were absent in mice without DAH. They also were absent in Nr4a1-/- mice, whereas Ly6CloCD138- monocytes were unaffected. However, Nr4a1-/- mice were susceptible to pristane-induced DAH and lung vasculitis, suggesting that disease onset does not require Ly6CloCD138- monocytes. Peritoneal Ly6CloCD138+ M{phi} were unchanged in Nr4a1-/- mice, indicating that they are not derived from Ly6CloCD138+ monocytes. We conclude that pristane-induced lung microvascular lung injury stimulates a wave of Nr4h1-dependent Ly6CloCD138+ patrolling monocytes in an ineffectual effort to maintain vascular integrity in the face of ongoing endothelial damage.

immunology↗

bioRxiv2021

Compensatory changes in contralesional node strength, brain wide modularity and cross-modular functional interactions in a rat model of traumatic brain injury

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicenter, across regions involved in affective, sensorimotor, and cognitive processing. Understanding how traumatic brain injury (TBI) reorganizes local and brain wide nodal functional interactions may provide valuable quantitative parameters for monitoring pathological progression and functional recovery. To this end, we investigated spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) signal obtained at 11.1 Tesla in rats sustaining controlled cortical impact (CCI) and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12,879 pairwise correlations between fMRI signals from 162 regions. Our data indicate that on days 2 and 30 post-CCI there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic, and basal forebrain areas. Rats imaged on day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality, and participation coefficient track early and late TBI effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to CCI may be unfavorable to brain wide communication in the early post-injury period.

neuroscience↗