Digital Commons Network^™

Neutropenia And Progenitor Cell Mobilization In Ap3-B1 Mutant Pearl Mice, Matthew Vallejo

All ETDs from UAB

Mutations in the AP3-ß1 gene are known to cause Hermansky-Pudlak syndrome type 2 (HPS2) in humans and canine cyclic hematopoiesis (CH) in gray collie dogs. HPS2 patients have severe congenital neutropenia (SCN), and dogs have cyclic neutropenia (CN). The mechanism behind neutropenia is uncertain. Pearl mice have an AP3-ß1 mutation, but whether they actually have neutropenia has not yet been evaluated. This dissertation presents a discussion of the evaluation of neutropenia in pearl mice, hematopoietic progenitor cell mobilization defect in pearl mice and finally an evaluation of methods of dog-to-mouse xenotransplantation to establish a xenotransplant model of the dog hematopoietic …

Hur Regulation In Central Nervous System Disorders, Crystal G. Wheeler

All ETDs from UAB

In inflammatory diseases of the central nervous system (CNS), astrocytes play a major role in the systemic response to disease by either enhancing or limiting the inflammatory response through secretion of growth factors or cytokines. HuR RNA binding protein regulates many genes involved in inflammation. Inflammatory diseases such as brain tumors, Amylotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), have been linked to HuR, by our laboratory and others. To determine whether astrocytic overexpression of HuR would regulate inflammation in diseases of the CNS, we designed a transgenic mouse in which the HuR gene is overexpressed. In the first study, …

Role Of Endothelial Mannose Residues In Monocyte Adhesion Under Flow, David Wayne Scott

All ETDs from UAB

Atherosclerosis is a chronic inflammatory disease of the vessel wall and underlying cause of most cardiovascular disease. Much is understood about the nature of atherosclerosis development, including contributions from leukocytes that drive the disease process forward. The general process by which leukocytes are trafficked to sites of atherosclerosis development, and sites of inflammation in general, is understood and relies upon endothelial expressed protein adhesion molecules which serve as ligands for cognate leukocyte receptors. While these adhesion molecules share the post-translation modification of N-glycosylation, relatively little is known as to what functional role these modification plays in: i) interactions of leukocytes …

Regulation Of Capsule By Cpsa And Global Regulatory Networks In Streptococcus Pneumoniae Type 2, Kanupriya Gupta

All ETDs from UAB

Streptococcus pneumoniae is a major human pathogen that can reside asymptomatically in the nasopharynx before causing invasive disease by entering systemic sites. This involves regulation of colonization and virulence factors including capsule. cps2A, the first gene of the capsule (cps) locus has been proposed to regulate capsule, however its exact role and mechanism is not well understood. A complete deletion of cps2A resulted in enhanced capsule levels, with no alteration in the transcription levels of cps genes. Complementation of Cps2A restored wild type levels of capsule. Expression of the C-terminal tail alone was able to partially complement the deletion strain, …

O-Linked Beta-N-Acetylglucosamine (O-Glcnac) And The Mitochondrion, Christopher Calderon

All ETDs from UAB

O-linked beta-N-acetylglucosamine (O-GlcNAc) is a dynamic and ubiquitous posttranslational modification of serine and threonine residues on nuclear and cytoplasmic proteins. O-GlcNAc has emerged as an important regulator of cellular processes such as cell signaling, transcription, translation, apoptosis, and cell cycle regulation, among others. O-GlcNAc is thought to be a contributor to pathologies such as hyperglycemia and insulin resistance. O-GlcNAc has been viewed as an indicator of cellular energy levels and is associated with diabetic complications under nutrient excess. Other studies have shown that a variety of stress stimuli increase the levels of protein O-GlcNAc in mammalian cells, and this increase …

Phospho-Erk And Amyloid Beta: Targets Of Estrogen In The Brain, Thomas Reed Peavy

All ETDs from UAB

Estrogen replacement therapy (ERT) has been shown to improve memory function in menopausal women, but increases hormone sensitive cancers, prompting a more targeted investigation of estrogen's action in learning and memory to develop more targeted therapeutics. Estrogen improves performance on the novel object recognition task by increasing phosphorylation of extracellular signal-regulated kinase (pERK) within minutes in the hippocampus. Dr. Lori McMahon's lab showed that the improvement in novel object recognition can be seen 24 hours after subcutaneous injection of proestrous levels of estrogen (referred to as E24). Whether a corresponding increase in pERK occurs at the E24 time point had …

The Origin, Regulation, And Function Of Tbet In Effector Cd4 T Cells During Chronic Autoimmune Disease, Wen-I Yeh

All ETDs from UAB

Multiple Sclerosis (MS) is an autoimmune disease resulting from aberrant immune cells causing demyelination. We utilize the well-studied mouse model, experimental autoimmune encephalomyelitis (EAE), to decipher the underlying pathogenesis of MS. Effector CD4 T-cells play a critical role during EAE because the disease is induced by adoptively transferring myelin-specific CD4 T-cells into naïve mice. Classically, effector CD4 T-cells have been divided into distinct subsets based on their functional properties: Th1 cells produce IFNγ, Th2 cells secrete IL-4, IL-5, and IL-13, Th17 cells make IL-17A, IL-17F, IL-21, and IL-22, and regulatory T cells produce IL-10. Th1 cells were originally identified as …

The Role Of Nr4a3 And Its Agonists In Skeletal Muscle Glucose Transport And Insulin Sensitivity, Qinglan Liu

All ETDs from UAB

Insulin resistance plays a central role in the pathogenesis of Type 2 Diabetes (T2DM) and involves diminished stimulation of glucose transport in skeletal muscle. Improvements in insulin sensitivity are essential for both prevention and treatment of T2DM. However, the limitation of current medications highlights the need for alternative molecular regulators of insulin action and developing new insulin sensitizers. Our laboratory has initially identified roles for the orphan nuclear receptor NR4A3 in insulin-sensitization and stimulation of glucose transport. However, the cellular effect and downstream mechanisms of NR4A3 and its agonists (e.g. 6-mercaptopurine/6-MP) on insulin effector system in skeletal muscle remain unknown. …

Investigation Of Death Receptor-5 Mediated Apoptosis And Inhibition Of Wnt/Ss-Catenin Signaling In Basal-Like Breast Cancer Stem Cells, Angelina Ix-Ik' Londono-Joshi

All ETDs from UAB

Basal-like breast cancers (BLBC) display aggressive clinical behavior attributed to the presence of cancer stem cells (CSCs). TRA-8, a monoclonal antibody that binds specifically to TRAIL death receptor 5, preferentially induces apoptosis in BLBC subtype cells; however it is unknown if TRA-8 is also cytotoxic to the CSC population. Moreover, some BLBC cell lines are resistant to TRA-8, and overcoming resistance is critical for clinical translation of this therapy. One potential approach to overcome TRA- 8 resistance is to target the Wnt/ß-catenin pathway. LRP6 is a cell surface receptor that is an indispensable element of the Wnt/ß-catenin signaling pathway that …

Influence Of Age On The Usage Of Family Planning Methods By Turkish Married Men Living In Southeastern Turkey, Sezer Kisa, Si̇mge Zeyneloğlu, Leyla Deli̇baş

Turkish Journal of Medical Sciences

Unintended pregnancy rates are still high in Turkey and family planning services have been directed mostly at women. The aim of this study was to assess the influence of age on the usage of family planning methods by Turkish married men. Materials and methods: A cross-sectional survey research design was used, including 1352 men aged 20-52 years who lived in the southeast of Turkey and whose wives were fertile, not menopausal, and had at least 1 child. A questionnaire was used to collect data. Descriptive statistics and multidimensional cross-tabs were used. Results: Men 40 years old and over used family …

Orthophenylphenol In Healthcare Environments: A Trial Related To A New Administration Method And A Review Of The Literature, Ali̇cem Teki̇n, Tuba Dal, Caferi̇ Tayyar Selçuk, Özcan Deveci̇, Recep Teki̇n, Mahmut Mete, Sai̇m Dayan, Sali̇h Hoşoğlu

Turkish Journal of Medical Sciences

To investigate antibacterial and antifungal effectiveness of orthophenylphenol (Fumispore, LCB, La Salle, France) with a new administration method in healthcare environments. Materials and methods: This study was performed in 3 units of the Dicle University Hospital. Surface swab and ambient air samples were collected just before the application of Fumispore and 6 h later. All samples were inoculated onto plate count agar and Sabouraud dextrose agar. The total aerobic colony count (ACC) was determined by using the standard method based on quantitative bacterial measurement. Results: In total, 30 surface swabs and 6 ambient air samples were collected. The mean values …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

Effects Of Cellular Heterogeneity And Immune Cells In Angiotensin Ii-Infused Hemorrhaged Ascending Aortas, Kyung Sik Jung

Theses and Dissertations--Toxicology and Cancer Biology

A previous thoracic aortic aneurysm time course study from our laboratory determined that ascending aortic dilation was significantly increased by day 5, and reached a plateau by day 28 of angiotensin II (AngII) infusion. We also found that mice had hemorrhage localized to the ascending aortas by day 5 of AngII infusion. The purpose of these studies was to provide mechanistic insight into the development of AngII-induced ascending aortic hemorrhage.

Male C57BL/6 mice fed normal diet were subcutaneously infused with either AngII (1000 ng/kg/min) or saline for 5 days. To examine cellular heterogeneity, hemorrhaged ascending aortas were collected and sectioned …

The Mr Imaging Features And The Analyses Of Quantitative Parameters In Cases With Surgically Repaired Tetralogy Of Fallot, Sali̇h Hamcan, Bülent Karaman, Bi̇lal Battal, Veysel Akgün, Kemal Kara, Tuncay Hazirolan, Uğur Bozlar

Turkish Journal of Medical Sciences

To present postoperative cardiac magnetic resonance (CMR) imaging features of cases of surgically repaired tetralogy of Fallot (TOF) and to evaluate the relationship among data used in follow-up procedures, such as right ventricular ejection fraction (RV-EF), pulmonary regurgitation fraction (PRF), and the degree of right ventricular (RV) dysfunction. Materials and methods: Fourteen patients (9 males and 5 females; mean age 11.9 ± 3.6 years) with surgically repaired TOF who were admitted to our clinic for follow-up CMR imaging between July 2008 and September 2011 were included in the study. A protocol that consisted of cine steady-state free precession (SSFP) and …

Investigations Of Als1 And Hwp1 Genes In Clinical Isolates Of Candida Albicans, Melek İnci̇, Mustafa Altay Atalay, Burçi̇n Özer, Ömer Evi̇rgen, Ni̇zami̇ Duran, Vi̇cdan Köksaldi Motor, Ayşe Nedret Koç, Yüsüf Önlen, Çeti̇n Kilinç, Süleyman Durmaz

Turkish Journal of Medical Sciences

To explore the presence of ALS1 and HWP1 genes by multiplex polymerase chain reaction (PCR) in Candida albicans strains. Materials and methods: By using the multiplex PCR method, the presence of agglutinin-like sequence 1 (ALS1) and hyphal wall protein 1 (HWP1) genes were investigated in 206 C. albicans strains that were isolated from various clinical samples. Phenotypic identification of slime formation by microplate and tube adherence tests was performed. Results: The presence of the ALS1 gene was detected in 53.9% of all strains, while the HWP1 gene was present in 5.3%. Slime formation was phenotypically detected in the 62.2% of …

Interferon Inducible Protein Ifi35 Negatively Regulates Rig-I Antiviral Signaling And Supports Vesicular Stomatitis Virus Replication, Anshuman Das, Phat X. Dinh, Debasis Panda, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In a genome-wide siRNA screen, we recently identified the interferon (IFN) inducible protein 35 (IFI35, also known as IFP35) as a factor required for VSV infection. Studies reported here were conducted to further understand the role and requirement of IFI35 in VSV infection. Consistent with the siRNA screening data, we found that depletion of IFI35 led to reduced VSV replication at the level of viral gene expression. Although no direct interaction of IFI35 with the viral replication machinery was observed, we found that IFI35 negatively regulated the host innate immune response and rescued poly(I:C)-induced inhibition of VSV replication. Promoter-driven reporter …

Hyperglycemia Induces Differential Change In Oxidative Stress At Gene Expression And Functional Levels In Huvec And Hmvec, Hemang Patel, Juan Chen, Kumuda C. Das, Mahendra Kavdia

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Endothelial dysfunction precedes pathogenesis of vascular complications in diabetes. In recent years, the mechanisms of endothelial dysfunction were investigated to outline strategies for its treatment. However, the therapies for dysfunctional endothelium resulted in multiple clinical trial failures and remain elusive. There is a need for defining hyperglycemia-induced endothelial dysfunction with both generic and specific dysfunctional changes in endothelial cells (EC) using a systems approach. In this study, we investigated hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated hyperglycemia-induced functional changes (superoxide (O₂‾), and hydrogen peroxide (H₂O₂) production and mitochondrial membrane polarization) …

Studies Of Regulated Exocytosis From Neuroendocrine Cells, Madhurima Das

Wayne State University Theses

In this thesis we study cargo release and fusion pore dilation during calcium triggered exocytosis and the co-localization of calcium sensing proteins essential for exocytosis, in neuroendocrine cells.

Pancreatic beta cells secrete several hormones, the most studied one being insulin. C-peptide is a protein which is co-stored with and secreted from the same vesicles as insulin. It is found in the soluble phase unlike insulin, which is found in the dense core. The pancreatic beta cells also secrete the Chromogranin B (CgB) which is mostly found in the dense cores of secretory vesicles. In chapter 1, we found that CgB, …

Insulin Effect On Rankl And Opg Expression In Human Osteoblast-Like Mg63 Cells, Huixin Wang, Xiaohuan Zhong

Turkish Journal of Medical Sciences

To investigate the effect of insulin on receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression in human osteosarcoma MG63 cells using real-time polymerase chain reaction. Materials and methods: MG63 cells were exposed to different concentrations of human recombinant insulin (1, 10, and 100 nM) for 24 h, and then the expression of RANKL and OPG mRNA was identified.After that, MG63 cells were exposed to tensile stress combined with 0 or 10 nM insulin respectively for 0, 3, 6, and 12 h, and then the expression of RANKL and OPG mRNA was identified. Human monocytes were cultured …

Rapid Identification Of Aeromonas Species In Stool Samples With Chromogenic Media And Matrix-Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry: An Institutional Experience, Işin Akyar, Si̇mge Can

Turkish Journal of Medical Sciences

To evaluate the routine use of chromogenic media together with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) in gastrointestinal infections caused by Aeromonas spp. as rapid, practical, cost-effective and reliable methods. Materials and methods: Between August 2007 and March 2012, a total of 13,194 stool specimens of patients were included in the study. The stool samples and the reference strains were inoculated onto Cefsulodin-Irgasan-Novobiocin agar, sheep blood agar, eosin-methylene blue agar, and Hektoen enteric agar media together with CHROMagar Salmonella Plus. All the Salmonella and Aeromonas suspected colonies were identified with an automated system (Phoenix) and MALDI-TOF. Results: …

The Correlation Between Metabolic Syndrome And Lower Urinary Tract Symptoms In Females, Cevdet Serkan Gökkaya, Cüneyt Özden, Bi̇nhan Kağan Aktaş, Hüseyi̇n Ci̇han Demi̇rel, Özer Güzel, Mehmet Karabakan, Aki̇f Ersoy Erkmen, Çeti̇n Volkan Özteki̇n, Ali̇ Memi̇ş

Turkish Journal of Medical Sciences

To evaluate the association between lower urinary tract symptoms (LUTS) and metabolic syndrome (MS) in women. Materials and methods: A total of 155 women with LUTS were included in the study. LUTS were evaluated using the International Prostate Symptom Score (IPSS) and the Bristol Female Lower Urinary Tract Symptoms (BFLUTS) questionnaire. Besides total IPSS, voiding and storage IPSS were calculated separately. Diagnosis of MS was made according to the consensus report of the International Diabetes Foundation. The patients were classified into 3 groups: those without MS (group 1), those with 3 risk factors of MS (group 2), and those with …

Does Adma Affect The Oxidant/Antioxidant Balance In Rats?, Hasan Alaçam, Bahatti̇n Avci, Osman Şaliş, Ahmet Di̇lek, Ahmet Kozan, Cuma Mertoğlu, Mehmet Şahi̇n, Ali̇ Okuyucu

Turkish Journal of Medical Sciences

Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide synthase (NOS). Oxidative stress might be defined as an imbalance between protein oxidation and antioxidants. Our aim was to determine in vivo whether ADMA causes oxidative damage. Materials and methods: Thirty rats were divided into 3 equal groups: a control group, a group administered 1 mg/kg ADMA, and a group administered 2 mg/kg ADMA. ADMA was administered intraperitoneally for 7 days. Malondialdehyde (MDA), protein carbonyl (PC) content, and nitrate+nitrite concentrations were measured with serum samples. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities were analyzed with plasma samples. Results: A …

Epidemiology, Clinical Features, And Laboratory Detection Of Mycoplasma Pneumoniae Infection In East Azerbaijan, Iran, Reza Ghotaslou, Simin Sharifi, Mohammad Taghi Akhi, Mohammad Hossein Soroush

Turkish Journal of Medical Sciences

Mycoplasma pneumoniae is involved in the etiology of many respiratory tract infections. This prospective study describes the epidemiology and clinical properties of M. pneumoniae infections in hospitals of the Tabriz University of Medical Sciences. Materials and methods: From May 2009 to November 2010, 200 patients with respiratory tract infections were enrolled into this study. Due to antibiotic use 51 patients were excluded. M. pneumoniae from respiratory infections was detected by culture, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) assays. Results: M. pneumoniae infection was detected in 9 (6.15%), 8 (5.3%), and 3 (2.01%) of patients by PCR, ELISA, …

Antimicrobial Susceptibilities Of Various Arcobacter Species, Ahmet Ünver, Hali̇l İbrahi̇m Atabay, Mi̇tat Şahi̇n, Özgür Çelebi̇

Turkish Journal of Medical Sciences

To determine the antimicrobial susceptibilities of various Arcobacter strains isolated from domestic geese, which have great potential for the transmission of arcobacters to humans and animals by contamination of water sources. Materials and methods: A total of 16 Arcobacter strains including A. cryaerophilus (7), A. skirrowii (7), and A. butzleri (2) were examined for their susceptibilities to 20 antibiotics using a disk-diffusion method. Results: All Arcobacter isolates tested were resistant to cloxacillin, cefazolin, optochin, vancomycin, and fusidic acid, and most were susceptible to oxytetracycline, chloramphenicol (except for A. butzleri), nitrofurantoin, amikacin, enrofloxacin, ofloxacin, erythromycin, ampicillin sulbactam, and amoxicillin (except for …

Cytokine Associated Neopterin Response Of Peripheral Blood Mononuclear Cells To In Vitro Epstein–Barr Virus Transformation Process Of B Lymphocytes, Lati̇fe Arzu Aral, Ayşegül Atak Yücel

Turkish Journal of Medical Sciences

The Epstein-Barr Virus (EBV) is a human herpes virus that infects B lymphocytes latently and immortalises the cells due to transformation. EBV infection is asymptomatic in childhood, while it may cause a self-limiting lymphoproliferative disorder in adolescence. This study aimed to show the association between in vitro transformation of B lymphocytes via EBV and the levels of neopterin with different accompanying cytokine responses. Materials and methods: Mononuclear cells were isolated from peripheral blood samples of healthy donors and transformed with an EBV secreting cell-line, B95-8. Neopterin, interferon (IFN)-\gamma, tumour necrosis factor (TNF)-\alpha, and interleukin (IL)-6 levels were measured in culture …

Evaluation Of Genexpert Vana/Vanb Assay For The Detection Of Vancomycin-Resistant Enterococci In Patients Newly Admitted To Intensive Care Units, Server Yağci, Çi̇ğdem Ataman Hati̇poğlu, Şeri̇fe Altun, Cemal Bulut, Zeli̇ha Koçak Tufan, Hati̇ce Uludağ Altun, Günay Ertem, Fatma Şebnem Erdi̇nç

Turkish Journal of Medical Sciences

The automated Cepheid GeneXpert system provides rapid PCR results and can be used for the identification of VRE. We aimed to evaluate the use of the Cepheid Xpert vanA/vanB real-time PCR assay for the detection of VRE from rectal swabs of patients newly admitted to intensive care units in a hospital setting. Materials and methods: Rectal swab samples of patients newly admitted to 6 intensive care units from March 2011 to February 2012 were obtained. The specimens were analyzed by the GeneXpert system. The results were reported for both vanA and vanB as negative or positive. Results: Comparing the number …

Influence Of Trace Elements And Their Correlation With Semen Quality In Fertile And Infertile Subjects, Vickram Sundaram, Muthugadhalli Srinivas, Jayaraman Gurunathan, Kamini Rao, Ramesh Pathy Maniyan, Sridharan Balasundaram

Turkish Journal of Medical Sciences

There has been increasing curiosity about the appraisal of essential trace elements present in human body fluids and their correlation to human health. Human seminal plasma contains several trace elements that have an imperative role in the normal functioning of the semen. As a result, it is very important to evaluate Zn and other trace elements present in the seminal plasma for the assessment of male infertility. The main objective of this research is to evaluate Zn concentrations and their intercorrelations with semen parameters such as sperm concentration, sperm motility, and normal morphology of the sperm, towards their contribution to …

Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel

Theses and Dissertations--Pharmacology and Nutritional Sciences

Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …

Sex Differences In Cell Death And Steroid Hormone Receptors In Cortical Explants, Amanda L. Trout

Theses and Dissertations--Physiology

Estrogens, such as the biologically active 17-b estradiol (E2) have many actions in the male and female brain. Not only does E2 regulate reproductive behavior in adults, it organizes and activates the brains of younger animals in a sex-specific manner. In addition, many human studies have shown E2 to provide protection against a variety of neurological disorders, including stoke. These studies have been controversial and depend largely on the type and timing of hormone replacement. Animal studies are much less controversial and clearly demonstrate a neuroprotective role for E2 following ischemic brain injury. Because much of E2 neuroprotection requires sex …