scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

GONADOTROPHIN PATTERNS IN MALE AND FEMALE RATS:

1968 ◽  
Vol 58 (4) ◽  
pp. 600-612 ◽  
Author(s):  
Robert Boyd ◽  
Donald C. Johnson
Keyword(s):  
Ascorbic Acid ◽  
Testosterone Propionate ◽  
Female Rats ◽  
Female Rat ◽  
Feedback Effects ◽  
Male And Female ◽  
Prostate Weight ◽  
Male And Female Rats ◽  
Males And Females ◽  
Normal Males

ABSTRACT The effects of various doses of testosterone propionate (TP) upon the release of luteinizing hormone (LH or ICSH) from the hypophysis of a gonadectomized male or female rat were compared. Prostate weight in hypophysectomized male parabiotic partners was used to evaluate the quantity of circulating LH. Hypophyseal LH was measured by the ovarian ascorbic acid depletion method. Males castrated when 45 days old secreted significantly more LH and had three times the amount of pituitary LH as ovariectomized females. Administration of 25 μg TP daily reduced the amount of LH in the plasma, and increased the amount in the pituitary gland, in both sexes. Treatment with 50 μg caused a further reduction in plasma LH in males, but not in females, while pituitary levels in both were equal to that of their respective controls. LH fell to the same low level in partners of males or females receiving 100 μg TP. When gonadectomized at 39 days, males and females had the same amount of plasma LH, but males had more stored hormone. Pituitary levels were unchanged from controls following treatment with 12.5, 25 or 50 μg TP daily, but plasma values dropped an equal amount in both sexes with the latter two doses. Androgenized males or females, gonadectomized when 39 days old, were very sensitive to the effects of TP and plasma LH was significantly reduced with 12.5 μg daily. Pituitary LH in androgenized males was higher than that of normal males but was reduced to normal by small amounts of TP. The amount of stored LH in androgenized females was not different from that of normal females and it was unchanged by any dose of TP tested. Results are consistent with the conclusion that the male hypothalamic-hypophyseal axis is at least as sensitive as the female axis to the negative feedback effects of TP. Androgenization increases the sensitivity to TP in both males and females.

scholarly journals Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Song ◽  
Fang Yuan ◽  
Xiaohong Li ◽  
Xipeng Ma ◽  
Xinmin Yin ◽  
...  
Keyword(s):  
Sex Differences ◽  
Microbial Activity ◽  
Hepatic Steatosis ◽  
Female Rats ◽  
Male Rats ◽  
Calorie Intake ◽  
Dietary Copper ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rrna Sequencing

Abstract Background Inadequate copper intake and increased fructose consumption represent two important nutritional problems in the USA. Dietary copper-fructose interactions alter gut microbial activity and contribute to the development of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to determine whether dietary copper-fructose interactions alter gut microbial activity in a sex-differential manner and whether sex differences in gut microbial activity are associated with sex differences in hepatic steatosis. Methods Male and female weanling Sprague-Dawley (SD) rats were fed ad libitum with an AIN-93G purified rodent diet with defined copper content for 8 weeks. The copper content is 6 mg/kg and 1.5 mg/kg in adequate copper diet (CuA) and marginal copper diet (CuM), respectively. Animals had free access to either deionized water or deionized water containing 10% fructose (F) (w/v) as the only drink during the experiment. Body weight, calorie intake, plasma alanine aminotransferase, aspartate aminotransferase, and liver histology as well as liver triglyceride were evaluated. Fecal microbial contents were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Fecal and cecal short-chain fatty acids (SCFAs) were determined by gas chromatography-mass spectrometry (GC-MS). Results Male and female rats exhibit similar trends of changes in the body weight gain and calorie intake in response to dietary copper and fructose, with a generally higher level in male rats. Several female rats in the CuAF group developed mild steatosis, while no obvious steatosis was observed in male rats fed with CuAF or CuMF diets. Fecal 16S rRNA sequencing analysis revealed distinct alterations of the gut microbiome in male and female rats. Linear discriminant analysis (LDA) effect size (LEfSe) identified sex-specific abundant taxa in different groups. Further, total SCFAs, as well as, butyrate were decreased in a more pronounced manner in female CuMF rats than in male rats. Of note, the decreased SCFAs are concomitant with the reduced SCFA producers, but not correlated to hepatic steatosis. Conclusions Our data demonstrated sex differences in the alterations of gut microbial abundance, activities, and hepatic steatosis in response to dietary copper-fructose interaction in rats. The correlation between sex differences in metabolic phenotypes and alterations of gut microbial activities remains elusive.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Aniline and hexobarbital hydroxylases from rat lung and kidney: neither sex dependent nor inducible with phenobarbital

1982 ◽  
Vol 60 (10) ◽  
pp. 1247-1250 ◽  
Author(s):  
Janet L. Lister ◽  
Bruce B. Virgo
Keyword(s):  
Microsomal Protein ◽  
Female Rats ◽  
Rat Lung ◽  
Male And Female ◽  
Aniline Hydroxylase ◽  
Protein Levels ◽  
Male And Female Rats ◽  
Males And Females ◽  
Cytochrome P 450 ◽  
Lung And Kidney

The basal activities of aniline hydroxylase (AH), hexobarbital hydroxylase (HH), and ethylmorphine N-demethylase (ED) were measured in the 9000 × g supernatant of kidneys and lungs from male and female rats. No ED activity was detected in any tissue although all tissues N-demethylated three other substrates. The activities of AH and HH were not sex dependent in either kidney or lung. Similarly, pulmonary and renal microsomal protein concentrations were independent of sex. In addition, cytochrome P-450 levels in the kidney were the same in males and females (pulmonary P-450 was not measured). The pulmonary hydroxylases were more active than the renal enzymes in both sexes. In males, phenobarbital (ip, 50 rng∙kg−1∙day−1 for 3 days) failed to induce AH or HH in either kidney or lung; it did not increase the weight or microsomal protein levels of these organs and it also failed to increase renal P-450. Thus, the basal activities of AH and HH in lungs and kidneys are not different in male and female rats and are not increased by phenobarbital.

P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stavrakis ◽  
K Elkholey ◽  
L Morris ◽  
Y Li ◽  
S S Po
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Sudden Death ◽  
Ejection Fraction ◽  
Female Rats ◽  
Autonomic Modulation ◽  
Preserved Ejection Fraction ◽  
Qtc Prolongation ◽  
Male And Female ◽  
Male And Female Rats

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic. Purpose To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes. Methods Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality. Results A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner. Conclusions Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.

Effect of long-term undernutrition on male and female rat diaphragm contractility, fatigue, and fiber types

1994 ◽  
Vol 76 (4) ◽  
pp. 1540-1547 ◽  
Author(s):  
D. J. Prezant ◽  
B. Richner ◽  
T. K. Aldrich ◽  
D. E. Valentine ◽  
E. I. Gentry ◽  
...  
Keyword(s):  
Weight Gain ◽  
Fatigue Resistance ◽  
Female Rats ◽  
Fiber Types ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Males And Females ◽  
Diaphragm Atrophy

The effects of long-term undernutrition (10 wk) on diaphragm contractility, fatigue, and fiber type proportions were studied in male and female rats. Contractility and fatigue resistance indexes were measured in an in vitro diaphragm costal strip preparation by using direct stimulation at 37 degrees C. Undernutrition allowed for continued growth in males and females but with substantial reductions in weight gain. Relative to control rats of the same sex, final weights were significantly lower in undernourished males (74 +/- 3%) than females (90 +/- 5%), but weight gain was not significantly different between undernourished males (58 +/- 5%) and females (60 +/- 3%). Only in males did undernutrition significantly reduce costal diaphragm weight (to 77 +/- 5% of control). Diaphragm forces, normalized for cross-sectional area, were not significantly different from male or female control values. Fatigue resistance indexes (fatigue/baseline force) were increased at all stimulation frequencies in undernourished males but not in undernourished females. Costal diaphragm atrophy, involving types I and II fibers, occurred in undernourished males but not in undernourished females. In conclusion, despite long-term undernutrition reducing weight gain to similar levels in males and females (relative to control), there was excellent preservation of diaphragm weight, function, and structure in females but, although diaphragm atrophy occurred, there was preserved contractility and increased fatigue resistance in males.

scholarly journals Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 424
Author(s):  
Perla Y. Gutiérrez-Arzapalo ◽  
Pilar Rodríguez-Rodríguez ◽  
David Ramiro-Cortijo ◽  
Marta Gil-Ortega ◽  
Beatriz Somoza ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Level ◽  
Female Rats ◽  
Resistance Artery ◽  
Male And Female ◽  
Maternal Undernutrition ◽  
Male And Female Rats ◽  
Males And Females ◽  
Artery Remodeling ◽  
Tail Cuff

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague–Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.

scholarly journals Drug induction of hepatic glutathione S-transferases in male and female rats*

1975 ◽  
Vol 146 (2) ◽  
pp. 351-356 ◽  
Author(s):  
N Kaplowitz ◽  
J Kuhlekamp ◽  
G Clifton
Keyword(s):  
Female Rats ◽  
Metabolizing Enzymes ◽  
Male And Female ◽  
Male And Female Rats ◽  
Hepatic Glutathione ◽  
Drug Induction ◽  
Glutathione S Transferases ◽  
Proportional Increase ◽  
Males And Females ◽  
Specific Activities

The induction of the glutathione S-transferases by phenobarbital and polycyclic hydrocarbons was studied in male and female rats. Administration of phenobarbital resulted in 60-80% increase in S-aryl and S-aralkyl enzyme specific activities, whereas the S-epoxide and S-alkyl activities were increased by 30-40%. In following the sequence of induction, the former two activities were noted to reach peak activities before an increase in the latter two activities was observed. Both 3-methylcholanthrene and 3,4-benzopyrene were shown toi nduce these four enzymic activities, although without the discrimination between pairs of activities noted with phenobarbital. No change in Km accompanied the increase in Vmax. after induction by drugs, and no change occurred in Ki for sulphobromophthalein inhibition. Significantly lower enzyme specific activities were found for three of the activities studied in female rats but no difference was observed in the S-alkyltransferase activity. However, the proportional increase in the enzymic activities in response to phenobarbital was the same in males and females. These studies demonstrate the drug induction of a group of cytosolic drug-metabolizing enzymes as well as the identification of sex differences in these activities.

Diet and 14CH3-Methionine Incorporation into Liver Phosphatidylcholine Fractions of Male and Female Rats

1971 ◽  
Vol 49 (1) ◽  
pp. 71-79 ◽  
Author(s):  
R. L. Lyman ◽  
G. Sheehan ◽  
J. Tinoco
Keyword(s):  
Sex Differences ◽  
Flaxseed Oil ◽  
Female Rats ◽  
Stock Diet ◽  
Choline Deficiency ◽  
Male And Female ◽  
Methyl Group ◽  
Degree Of Unsaturation ◽  
Male And Female Rats ◽  
Purina Chow

An experiment was conducted to see whether diet influenced the incorporation of 14CH3-methionine into liver phosphatidylcholines of male and female rats.Rats of both sexes were fed either a stock diet (Purina Chow), a semipurified diet containing 10% flaxseed oil, or a low methionine diet with or without choline. One hour before killing, 14CH3-methionine was injected into the animals. The distribution of the label in subfractions of liver phosphatidylcholines was then determined.Choline phosphatides of female rats fed chow or flaxseed oil diets had higher specific activities than did those of males. In chow-fed female rats the additional radioactivity appeared mainly in the tetraene phosphatidylcholine fraction. In female rats fed flaxseed oil, the extra label appeared in the tetraene as well as in a pentaene fraction.Therefore, changes in the degree of unsaturation of the species of phosphatidylcholine by dietary modification did not alter total incorporation of the label into liver phosphatidylcholines nor did it influence sex differences in the incorporation even though the distribution of the label within particular species of choline phosphatides was changed.No sex differences in incorporation were evident in the low methionine diet whether it contained choline or not. Choline deficiency did not affect total incorporation of the methyl group nor the proportions of phosphatidylcholine subfractions in the phospholipids, although in males it depressed the amount of hepatic phosphatidylcholine.

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