Identifying clinical phenotypes of frontotemporal dementia in post-9/11 era veterans using natural language processing.

Introduction: Frontotemporal dementia (FTD) encompasses a clinically and pathologically diverse group of neurodegenerative disorders, yet little work has quantified the unique phenotypic clinical presentations of FTD among post-9/11 era veterans. To identify phenotypes of FTD using natural language processing (NLP) aided medical chart reviews of post-9/11 era U.S.

Comorbidity and polypharmacy impact neurobehavioral symptoms and symptom validity failure among post-9/11 veterans with mild traumatic brain injury.

Objective: The study aimed to examine the association between post-concussive comorbidity burdens [post-traumatic stress disorder (PTSD), depression, and/or headache] and central nervous system (CNS) polypharmacy (five or more concurrent medications) with reported neurobehavioral symptoms and symptom validity screening among post-9/11 veterans with a history of mild traumatic brain injury (mTBI).

Setting: Administrative medical record data from the Department of Veterans Affairs (VA) were used in the study.

Participants: Post-9/11 veterans with mTBI and at least 2 years of VA care between 2001 and 2019 who had completed the comprehensive traumatic brain injury evaluation (CTBIE) were included in the study.

The Military Injuries: Understanding Post-Traumatic Epilepsy Study: Understanding Relationships among Lifetime Traumatic Brain Injury History, Epilepsy, and Quality of Life.

Understanding risk for epilepsy among persons who sustain a mild (mTBI) traumatic brain injury (TBI) is crucial for effective intervention and prevention. However, mTBI is frequently undocumented or poorly documented in health records. Further, health records are non-continuous, such as when persons move through health systems (e.

Contrast enhanced magnetic resonance imaging highlights neurovasculature changes following experimental traumatic brain injury in the rat.

Neurovascular injury has been proposed as a universal pathological hallmark of traumatic brain injury (TBI) with molecular markers of angiogenesis and endothelial function associated with injury severity and morbidity. Sex differences in the neurovasculature response post-TBI may contribute to the differences seen in how males and females respond to injury. Steady-state contrast enhanced magnetic resonance imaging (SSCE-MRI) can be used to non-invasively assess the neurovasculature and may be a useful tool in understanding and predicting outcomes post-TBI.

Pericytes improve locomotor recovery after spinal cord injury in male and female neonatal rats.

Objective: It is not known how activation of the hypoxia-inducible factor (HIF) pathway in pericytes, cells of the microvascular wall, influences new capillary growth. We tested the hypothesis that HIF-activated pericytes promote angiogenesis in a neonatal model of spinal cord injury (SCI).

Methods: Human placental pericytes stimulated with cobalt chloride and naïve pericytes were injected into the site of a thoracic hemi-section of the spinal cord in rat pups on postnatal day three (P3).

Sodium selenate retards epileptogenesis in acquired epilepsy models reversing changes in protein phosphatase 2A and hyperphosphorylated tau.

There are no treatments in clinical practice known to mitigate the neurobiological processes that convert a healthy brain into an epileptic one, a phenomenon known as epileptogenesis. Downregulation of protein phosphatase 2A, a protein that causes the hyperphosphorylation of tau, is implicated in neurodegenerative diseases commonly associated with epilepsy, such as Alzheimer's disease and traumatic brain injury. Here we used the protein phosphatase 2A activator sodium selenate to investigate the role of protein phosphatase 2A in three different rat models of epileptogenesis: amygdala kindling, post-kainic acid status epilepticus, and post-traumatic epilepsy.

The connexin 43/ZO-1 complex regulates cerebral endothelial F-actin architecture and migration.

Endothelial cell migration is a fundamental process during angiogenesis and, therefore, a point of intervention for therapeutic strategies aimed at controlling pathologies involving blood vessel growth. We sought to determine the role of the gap junction protein connexin 43 (Cx43) in key features of angiogenesis in the central nervous system. We used an in vitro model to test the hypothesis that a complex of interacting proteins, including Cx43 and zonula occludens-1 (ZO-1), regulates the migratory behavior of cerebral endothelium.

Driving the Hypoxia-Inducible Pathway in Human Pericytes Promotes Vascular Density in an Exosome-Dependent Manner.

Objectives: The mechanisms involved in activating pericytes, cells that ensheath capillaries, to engage in the formation of new capillaries, angiogenesis, remain unknown. In this study, the hypothesis was tested that pericytes could be stimulated to promote angiogenesis by driving the HIF pathway.

Methods: Pericytes were stimulated with CoCl2 to activate the HIF pathway.

Alterations of retinal vasculature in cystathionine-β-synthase heterozygous mice: a model of mild to moderate hyperhomocysteinemia.

Mild to moderate hyperhomocysteinemia is prevalent in humans and is implicated in neurovascular diseases, including recently in certain retinal diseases. Herein, we used hyperhomocysteinemic mice deficient in the Cbs gene encoding cystathionine-β-synthase (Cbs(+/-)) to evaluate retinal vascular integrity. The Cbs(+/+) (wild type) and Cbs(+/-) (heterozygous) mice (aged 16 to 52 weeks) were subjected to fluorescein angiography and optical coherence tomography to assess vasculature in vivo.

Homocysteine disrupts outgrowth of microvascular endothelium by an iNOS-dependent mechanism.

Objective: To test the hypothesis that Hcy impairs angiogenic outgrowth through an iNOS-dependent mechanism.

Methods: Adult C57Bl/6 mouse choroid explants were used in angiogenic outgrowth assays. Mouse microvascular endothelial cells were studied in culture during scrape-induced migration and dispersed cell locomotion experiments.

Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-); Het) were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+); WT).

Nitrative stress in cerebral endothelium is mediated by mGluR5 in hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) disrupts nitric oxide (NO) signaling and increases nitrative stress in cerebral microvascular endothelial cells (CMVECs). This is mediated, in part, by protein nitrotyrosinylation (3-nitrotyrosine; 3-NT) though the mechanisms by which extracellular homocysteine (Hcy) generates intracellular 3-NT are unknown. Using a murine model of mild HHcy (cbs(+/-) mouse), we show that 3-NT is significantly elevated in cerebral microvessels with concomitant reductions in serum NO bioavailability as compared with wild-type littermate controls (cbs(+/+)).