A5043430406- Neuroinflammation and Neurodegeneration Mechanisms
- Estrogen and related hormone effects
- Atherosclerosis and Cardiovascular Diseases
- Nitric Oxide and Endothelin Effects
- Inflammatory mediators and NSAID effects
- Sphingolipid Metabolism and Signaling
- Hormonal and reproductive studies
- Eicosanoids and Hypertension Pharmacology
- Menopause: Health Impacts and Treatments
- Chemotherapy-induced cardiotoxicity and mitigation
- Acute Ischemic Stroke Management
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Barrier Structure and Function Studies
- Autophagy in Disease and Therapy
- Intracerebral and Subarachnoid Hemorrhage Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Nanoplatforms for cancer theranostics
- Muscle Physiology and Disorders
- S100 Proteins and Annexins
- Neurological Disease Mechanisms and Treatments
- High Altitude and Hypoxia
- Heme Oxygenase-1 and Carbon Monoxide
- NF-κB Signaling Pathways
University of Arizona
2015-2024
University of Phoenix
2010-2022
University of California, Irvine
2004-2008
University of New Mexico
1997-2008
East Carolina University
1996
Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of has been linked to worse stroke outcomes, it remains unclear what extent by mechanisms activated influence ischemia-induced inflammation injury in the brain. Using a mouse model transient focal cerebral reperfusion, we demonstrated that via administration dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits brain...
The present study was undertaken to determine the efficacy of coadministration fingolimod with alteplase in acute ischemic stroke patients a delayed time window.This prospective, randomized, open-label, blinded endpoint clinical trial, enrolling internal carotid artery or middle cerebral proximal occlusion within 4.5 6 hours from symptom onset. Patients were randomly assigned receive alone fingolimod. All underwent pretreatment and 24-hour noncontrast computed tomography (CT)/perfusion CT/CT...
BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use limited due a restricted time window risk, which in part may involve of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study’s overall aim was...
We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest CH is associated increased endothelial synthase (eNOS) activity within the vasculature. In addition, correlation of pressure selectively responsiveness EDNO-mediated suggests hypertension, rather than per se, a...
Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in periphery or several neurological diseases. However, whether autoimmune emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that facilitates genesis of autoimmunity aggravates ischemic injury.Using a mouse strain harbors transgenic T-cell receptor antigen, MOG35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined...
Little is known about vascular effects of testosterone. We previously reported chronic testosterone treatment increases tone in middle cerebral arteries (MCA; 300 microm diameter) male rats. In the present study, we investigated hypothesis that physiological levels circulating affect endothelial factors modulate cerebrovascular reactivity. Small branches MCA (150 were isolated from orchiectomized (ORX) and testosterone-treated (ORX+T) Intraluminal diameters recorded after step changes...
We previously showed that testosterone, administered in vivo, increases the tone of cerebral arteries. A possible underlying mechanism is increased vasoconstriction through thromboxane A2 (TxA2) pathway. Therefore, we investigated effect chronic testosterone treatment (4 wk) on TxA2 synthase levels and contribution to vascular rat middle arteries (MCAs). Using immunofluorescence confocal microscopy, demonstrated present MCA segments both smooth muscle endothelial layers. Western blot...
Tissues from males can be regulated by a balance of androgenic and estrogenic effects because local metabolism testosterone expression relevant steroid hormone receptors. As critical first step to understanding sex influences in the cerebral circulation males, we investigated presence enzymes that metabolize active products their respective We found blood vessels male rats express 5α-reductase type 2 aromatase, responsible for conversion into dihydrotestosterone (DHT) 17β-estradiol,...
Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory immune responses participate in ischemic brain injury, the molecular regulators neuroinflammation after remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized mitochondrial outer membrane predominantly expressed glia within central nervous system during conditions. This study investigated effect TSPO agonist, etifoxine, on injury ischemia/reperfusion. We used...
Our previous studies show that long-term testosterone treatment augments vascular tone under physiological conditions and exacerbates endotoxin-induced inflammation in the cerebral circulation. However, can be metabolized by aromatase to estrogen, evoking a balance between androgenic estrogenic effects. Therefore, we investigated effect of nonaromatizable androgen receptor agonist, dihydrotestosterone (DHT), on inflammatory nuclear factor-κB (NFκB) pathway blood vessels. Cerebral arteries...
P-glycoprotein (Pgp), a multiple drug resistance transporter expressed by vascular endothelial cells, is key component of the blood-brain barrier and has been shown to increase after inflammation. The nonaromatizable androgen, dihydrotestosterone (DHT), decreases inflammatory markers in smooth muscle independent androgen receptor (AR) stimulation. principal metabolite DHT, 5α-androstane-3β,17β-diol (3β-diol), activates estrogen (ER)β similarly cells. Therefore, we tested hypothesis that...
Past studies have demonstrated that 17β-estradiol (E 2 β) increases endothelial nitric oxide (NO) synthase (eNOS) activity in uterine, heart, and skeletal muscle cultured human cells. However, little is known about E β regulation of NO synthesis the pulmonary vasculature. The present study evaluated eNOS function arteries thoracic aortas. We hypothesized upregulates vascular release by increasing expression. To test this, NO-dependent vasodilation was assessed isolated perfused lungs aortic...
Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent an stimulus. Little is known about inflammation human tissues. Therefore, we tested hypothesis DHT alters COX-2 absence presence induced primary coronary artery smooth muscle cells...
This study evaluated the activity and content of cyclooxygenase (COX)-1 -2 in response to acute resistance exercise (RE) human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is primary COX isoform elevated with activity, however, has been assessed after humans. It was hypothesized RE would increase COX-1 COX-2 activity. Muscle biopsies were taken from vastus lateralis nine young men (25 ± 1 yr) at baseline (preexercise), 4, 24 h a single bout knee extensor (three sets 10...
This study aimed to assess the ability for exercise training performed before and during biweekly doxorubicin (DOX) administration attenuate adverse effects of DOX on skeletal muscle. We hypothesized that treatment would increase REDD1, impair mammalian target rapamycin (mTOR) signaling, reduce muscle fiber size, these responses.Eight-week-old ovariectomized female Sprague-Dawley rats were randomized one four treatments: + (Ex-Dox), Ex vehicle (Ex-Veh), sedentary (Sed-Dox), Sed Veh...
Stroke-induced immune suppression predisposes the host to infections and can contribute high morbidity mortality in stroke patients. Because ischemic has a profound effect on systemic response, which may explain increased susceptibility of patients infection, an urgent need persists for better understanding mechanisms associated with suppression; new effective treatments then be identified. NK cells play key role early defense against pathogens by killing infected and/or producing cytokines...
Severe traumatic brain injury (TBI) results in cognitive dysfunction 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 and cerebrovascular function assessed their interrelationships. Sprague-Dawley rats received midline fluid percussion (n = 20) or sham 21). Cognitive was (3- 6-month novel object recognition [NOR], location [NOL], temporal order [TOR]). Six-month cerebral...
Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1α (HIF-1α) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1α and following or with glucose deprivation (HGD) cerebral vasculature. levels were assessed via Western blot, was indirectly measured a DNA binding assay. Experiments performed using arteries isolated from castrated male rats treated vivo...