Biology subjects

Griffiths, D. R.

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

4 recordsLinked to original sources

bioRxiv2026

Subacute and Chronic Cognitive and Cerebrovascular Functional Consequences of Mild Traumatic Brain Injury in Rats

Traumatic brain injury (TBI) is the main cause of death and disability in the United States in people younger than 35 years old and is a common cause of wartime injuries. Mild TBI (mTBI) is a predisposing factor for later development of dementia and cerebrovascular disease. Aerobic exercise was reported to improve cognitive function in chronic TBI through improved vascular function. The aims of the study are to characterize and correlate the subacute (10 weeks) and chronic (12 months) cognitive and cerebrovascular functional impairment following mTBI and evaluate the modulating effect of exercise early or late following mTBI on these changes. Sprague-Dawley rats received midline fluid percussion injury or sham procedure and followed for 10 weeks or 12 months with a subgroup of mTBI rats undergoing 5-week treadmill aerobic exercise 2 weeks (early) or 10 months (late) post-injury for 6 weeks. Cognitive function was assessed using novel object recognition (NOR) and novel object location (NOL) tests. Regional cerebral blood volume (CBV) and cerebrovascular reactivity following hypercapneic stimulation (CVR) using contrast magnetic resonance imaging (MRI) and ex vivo pial artery vasoreactivity to intraluminal pressure, angiotensin II and diethylenetriamine NONOate (DETA NONOate) were measured. There was no difference in NOR or NOL at 10 weeks between mTBI and sham. NOR, but not NOL, was reduced in mTBI rats at 12 months. CBV at 10 weeks was higher in the primary somatosensory trunk cortex (trunk) and dentate gyrus regions in mTBI, but not at 12 months. CVR was lower in the trunk region of mTBI rats at 12 months. Compared to sham response at 10 weeks, there was impaired arterial constriction response to 90 mm Hg intraluminal pressure in mTBI rats at 10 weeks and in sham and mTBI rats at 12 months, with no difference seen in response to angiotensin II or DETA-NONOate exposure. There was no correlation between cognitive and vascular outcomes at 10 weeks or 12 months. Early or late exercise did not affect 12-month cognitive or vascular function following mTBI. The study showed chronic impairment in short-term memory cognitive function, regional cerebrovascular reactivity and early onset of impaired cerebrovascular myogenic response in rats subjected to mTBI. The findings of persistent cognitive and cerebrovascular impairment in this animal model enhance our understanding of the long-term consequence of mTBI.

neuroscience↗

bioRxiv2025

Community and functional stability in a working bioreactor degrading 1,4-dioxane at the Lowry Landfill Superfund Site

1,4-dioxane (dioxane) is an emerging contaminant that poses risks to human and environmental health. Bacterial dioxane degradation is increasingly being studied as a method to remove dioxane from contaminated water. However, there is a lack of studies on microbial community structures and functions within efficient, large scale, biodegradation-based remediation technologies. The Lowry Landfill Superfund Site (Colorado, USA) uses an on-site, pump-and-treat facility to remove dioxane from contaminated groundwater by biodegradation. Here, 16S rRNA and shotgun metagenomic sequencing were used to describe microbial community composition, soluble di-iron monooxygenase (SDIMO) alpha hydroxylases, and potential for dioxane degradation and horizontal gene transfer in bioreactor support media from the facility. Support media showed diverse microbial communities dominated by Nitrospiraceae, Nitrososphaeraceae, and Nitrosomonadaceae. Pseudonocardia were also detected, suggesting a potential presence of known dioxane-degraders. Candidate SDIMOs belonged mostly to Group V, followed by Groups IV, II, and I (based on read depth). The most abundant Group V clade contained 38 proteins that were phylogenetically related to DxmA-like proteins, including that of Pseudonocardia dioxanivorans CB1190 (a known dioxane degrader). Seventeen Lowry contigs containing DxmA-like proteins contained protein-coding genes potentially involved in chemical degradation, transcriptional regulation, and chemical transport. Interestingly, these contigs also contained evidence of potential horizontal gene transfer, including toxin-antitoxin proteins, phage integrase proteins, putative transposases, and putative miniature inverted-repeat transposable elements. These findings improve our understanding of potential dioxane biodegradation mechanisms in a functioning remediation system. Further studies are needed to definitively confirm microbial activity and enzymatic activity towards dioxane removal in this site. IMPORTANCEAs an environmental contaminant, 1,4-dioxane poses risks for water quality and human health. Used as a solvent and chemical stabilizer in a variety of manufacturing and industrial applications, microbiological methods of detoxification and mitigation are of interest. The degradation of 1,4-dioxane by the bacterium Pseudonocardia spp. is the best understood example; however, these studies are largely based on single isolate, bench-scale, or in silico experiments. Consequently, a knowledge gap exists on bacterial degradation of 1,4-dioxane at environmentally relevant concentrations using functioning remediation technologies at scale. This study addresses this gap directly by describing microbial taxa, enzymes, and potential horizontal gene transfer mechanisms associated with an active treatment plant located on a 1,4-dioxane-impacted U.S. Environmental Protection Agency (EPA) superfund site. As 1,4-dioxane contamination gains more attention, these findings may prove useful for future facilities aiming to promote and optimize removal by biodegradation.

microbiology↗

bioRxiv2022

Chronic Cognitive and Cerebrovascular Function Following Mild Traumatic Brain Injury in Rats

Severe traumatic brain injury results in cognitive dysfunction in part due to vascular perturbations. In contrast, the long-term vasculo-cognitive pathophysiology of mild TBI (mTBI) remains unknown. We evaluated mTBI effects on chronic cognitive and cerebrovascular function and assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion injury (N=20) or sham (N=21). Cognitive function was assessed (3- and 6-month novel object recognition (NOR), novel object location (NOL) and temporal order object recognition (TOR)). 6-month cerebral blood flow (CBF) and blood volume (CBV) using contrast MRI and ex vivo pial artery endothelial and smooth muscle-dependent function were measured. mTBI rats showed impaired NOR, with similar (non-significant) trends in NOL/TOR. Regional CBF and CBV were similar in sham and mTBI. NOR correlated with CBF in lateral hippocampus, medial hippocampus and primary somatosensory barrel cortex while inversely correlating with arterial smooth muscle-dependent dilation. 6-month baseline endothelial and smooth muscle-dependent arterial function were similar among mTBI and sham, but post-angiotensin II stimulation, mTBI showed no change in smooth muscle-dependent dilation from baseline response, unlike the reduction in sham. mTBI led to chronic cognitive dysfunction and altered angiotensin II-stimulated smooth muscle-dependent vasoreactivity, a paradigm that could advance understanding of the long-term sequelae of human mild TBI.

neuroscience↗

bioRxiv2019

Diffuse TBI-induced expression of anxiety-like behavior coincides with altered glutamatergic function, TrkB protein levels and region-dependent pathophysiology in amygdala circuitry

Up to 50% of traumatic brain injury (TBI) survivors demonstrate persisting affective symptoms indicative of limbic system dysregulation, yet the pathophysiology underlying the symptoms is unclear. We hypothesize that TBI-induced pathophysiologic changes within distinct amygdala nuclei contribute to the expression of late-onset anxiety-like behavior. Adult, male Sprague-Dawley rats underwent midline fluid percussion injury or sham surgery. Anxiety-like behavior was assessed at 7 and 28 days post-injury (DPI) followed by assessment of real-time glutamate neurotransmission in the basolateral amygdala (BLA) and central nucleus of the amygdala (CeA) using glutamate-selective microelectrode arrays. In separate animal cohorts, the presence of neuropathology, astrocytosis, and microglial activation were assessed at 1, 7, and 28DPI. Protein levels of glutamatergic transporters (Glt-1, GLAST) and presynaptic modulators of glutamate release (mGluR2, TrkB, BDNF, and glucocorticoid receptors) were quantified using automated capillary western techniques at 28DPI. The expression of anxiety-like behavior at 28DPI coincided with decreased glutamate release and slower glutamate clearance in the CeA, not BLA. Changes in glutamate neurotransmission were independent of protein levels of glutamate transporters and mGluR2 receptors, neuropathology, and astrocytosis. At 1DPI, microglia in the CeA demonstrated a neuroinflammatory response. BDNF and TrkB were decreased at 28DPI in the amygdala. These data indicate that diffuse axonal injury instigates sequences of molecular, structural and functional changes in the amygdala that contribute to circuit dysregulation relevant to the expression of affective disorders. Translationally, diffuse axonal injury can influence severity and incidence of affective symptoms and should be addressed in the history of patients with affective disorders.

neuroscience↗