scholarly journals Effects of Combined Oral Conjugated Estrogens and Medroxyprogesterone Acetate on Brain Infarction Size after Experimental Stroke in Rat

2005 ◽  
Vol 25 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Marguerite T Littleton-Kearney ◽  
Judy A Klaus ◽  
Patricia D Hurn
Keyword(s):  
Brain Infarction ◽  
Brain Regions ◽  
Interactive Effects ◽  
Ovariectomized Rats ◽  
Experimental Stroke ◽  
Beneficial Effects ◽  
Infarction Volume ◽  
Conjugated Equine Estrogens ◽  
Subcortical Regions ◽  
Equine Estrogens

The reason that estrogen is strongly protective in various estrogen-deficient animal models while seemingly detrimental in postmenopausal women remains unclear. It hypothesized that prolonged oral medroxyprogesterone (MPA) plus oral conjugated equine estrogens (CEE) diminishes estrogen ability to reduce stroke damage in the rodent stroke model. To test the hypothesis, we fed ovariectomized rats CEE or MPA, or a combination of CEE and MPA (CEP), before inducing 120 min of reversible focal stroke, using the intraluminal filament model. After 22 h reperfusion, the brains were harvested and infarction volumes were quantified. Treatment with CEE alone or with CEP reduced cortical infarction volume. However, CEP failed to provide ischemic protection in subcortical regions. It was concluded that CEE alone, or with CEP, is neuroprotective in the cortex, but interactive effects between the hormones may counteract CEE beneficial effects in subcortical brain regions.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals HIV Infection Is Associated with Attenuated Frontostriatal Intrinsic Connectivity: A Preliminary Study

2015 ◽  
Vol 21 (3) ◽  
pp. 203-213 ◽  
Author(s):  
Jonathan C. Ipser ◽  
Gregory G. Brown ◽  
Amanda Bischoff-Grethe ◽  
Colm G. Connolly ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Brain Regions ◽  
Group Differences ◽  
Hiv Rna ◽  
Functional Connections ◽  
Intrinsic Connectivity ◽  
Dorsolateral Prefrontal ◽  
Independent Replication ◽  
Subcortical Regions ◽  
The Brain

AbstractHIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. (JINS, 2015, 21, 1–11)

The effects of conjugated equine estrogens plus cyclical dydrogesterone on serum lipoproteins and apoproteins in postmenopausal women

1988 ◽  
Vol 117 (3) ◽  
pp. 339-342 ◽  
Author(s):  
C. D. Fletcher ◽  
E. Farish ◽  
M. M. Dagen ◽  
F. Alazzawi ◽  
D. McQueen ◽  
...  
Keyword(s):  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Postmenopausal Women ◽  
Hormone Replacement ◽  
Hdl Cholesterol ◽  
Serum Lipoproteins ◽  
Conjugated Equine Estrogens ◽  
The Individual ◽  
Equine Estrogens

Abstract. erum lipoprotein and apoprotein concentrations were monitored for 24 weeks in 26 postmenopausal women treated with conjugated equine estrogens (0.625 mg/day) with the addition of dydrogesterone (10 mg/day) for the last 12 days of each 28 day cycle. The women had had no previous hormone replacement therapy. The estrogen plus dydrogesterone regimen caused significant (P < 0.05) increases in triacylglycerol and HDL cholesterol concentrations. Both HDL2 and HDL3 cholesterol were increased. There were no other significant changes in lipoprotein concentrations. Both apoprotein AI and apoprotein All concentrations increased significantly (P < 0.05) over the study period. The ratios of apoprotein AI to apoprotein All, apoprotein AI to HDL cholesterol and apoprotein All to HDL cholesterol did not change. At the doses employed in this study, the use of dydrogesterone as a progestogen alters the effects of conjugated equine estrogens on lipoproteins and reinforces the view that the effects of a combined HRT regimen cannot be predicted from a consideration of the effects of the individual components.

Ameliorative effect of low-dose spironolactone on obesity and insulin resistance is through replenishment of estrogen in ovariectomized rats

2019 ◽  
Vol 97 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Lawrence A. Olatunji ◽  
Oluwaseun A. Adeyanju ◽  
Olugbenga S. Michael ◽  
Taofeek O. Usman ◽  
Rita C. Tostes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Low Dose ◽  
Glycogen Synthase ◽  
Mass Gain ◽  
Ovariectomized Rats ◽  
Atherogenic Dyslipidemia ◽  
Beneficial Effects ◽  
Ovx Rats ◽  
Ameliorative Effect ◽  
Hormonal Therapies

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-β, 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17β-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.

scholarly journals Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction

2017 ◽  
Vol 23 (6) ◽  
pp. 594-600 ◽  
Author(s):  
FB Cabral ◽  
LH Castro-Afonso ◽  
GS Nakiri ◽  
LM Monsignore ◽  
SRC Fábio ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Brain Infarction ◽  
Internal Capsule ◽  
Brain Regions ◽  
Hemorrhagic Transformation ◽  
Anterior Circulation ◽  
Caudate Nuclei ◽  
Predictive Values ◽  
Cortical Regions

Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

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