Biology subjects

Law, L. M.

Publications and source records attributed to Law, L. M..

3 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↗

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↗

bioRxiv2018

Hippocampal State Transitions at the Boundaries between Trial Epochs

The hippocampus encodes distinct environmental and behavioral contexts with unique patterns of activity. Representational shifts with changes in the context, referred to as remapping, have been extensively studied. However, less is known about the nature of transitions between representations. In this study, we leverage a large dataset of 2056 neurons recorded while rats performed an olfactory memory task with a predictable temporal structure involving trials and inter-trial intervals, separated by salient boundaries at the trial start and trial end. We found that trial epochs were associated with stable hippocampal population representations, despite moment to moment variability in stimuli and behavior. Representations of trial and inter-trial interval epochs were far more distinct than spatial factors would predict and the transitions between the two were abrupt, with a sharp boundary suggestive of a dynamic shift in the representational state. This boundary was associated with a large spike in multi-unit activity, with many individual cells specifically active at the start or end of each trial. Both epochs and boundaries were encoded by hippocampal populations, and these representations carried information on orthogonal axes readily identified using principal component analysis. We suggest that the activity spike at trial boundaries might serve to drive hippocampal activity from one stable state to another, and may play a role in segmenting continuous experience into discrete episodic memories.

neuroscience↗