Abstract T P81: Long-Term Activity Levels Vary by Rat Strain Following Stroke: A Disruption of the Circadian Rhythm?

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Allison Kunze ◽  
Dannielle Zierath ◽  
Olga Drogomiretskiy ◽  
Brett Jaspers ◽  
Tessa Barclay ◽  
...  

Background: Assessment of long-term behavioral outcome after experimental cerebral ischemia is important for evaluating potential therapeutic interventions. In this study, we explored strain related differences in baseline behavior and in response to stroke. Methods: Spontaneous cage activity was monitored (cm moved per hr) and analyzed before and after 2 hour middle cerebral artery occlusion (MCAO) in male Lewis, Wistar, and Sprague Dawley (SD) rats using the Noldus PhenoTyper® cages and EthoVision® Software system. Stroke severity was assessed using the neuroscore, foot fault errors, and performance on the rotarod. Infarct volume at 24 hours was determined in a second cohort of animals. Animals were sacrificed 56 days after MCAO. Data are analyzed using non-parametric statistics. Results: Prior to stroke, the median distance moved per hour during the dark was similar among the 3 strains, but Lewis rats were more active during the light cycle (P=0.001). Neuroscores did not differ between strains at 3 hrs after MCAO nor did infarct volumes at 24 hours after MCAO. Lewis rats, however, performed worse on the rotarod in the month following MCAO (P<0.05 at each time point). Foot fault errors were similar throughout the study period. After stroke, Lewis rats became more active during the dark cycle while Wistar and SD rats became more active during the light cycle (Figure). Summary: The 3 strains of rats evaluated in this study had different patterns in the change in activity after MCAO. Lewis rats showed an increase in activity during the dark cycle while Wistar and SD rats showed an increase in activity during the light cycle. This observation suggests that there are genetic differences in the response to stroke that may alter the circadian rhythm after stroke.

2021 ◽  
pp. 1-20
Author(s):  
Juandré Lambertus Bernardus Saayman ◽  
Stephanus Frederik Steyn ◽  
Christiaan Beyers Brink

Abstract Objective: To investigate the long-term effects of juvenile sub-chronic sildenafil (SIL) treatment on the depressive-like behaviour and hippocampal brain-derived neurotrophic factor (BDNF) levels of adult Sprague-Dawley (SD) versus Flinders Sensitive Line (FSL) rats. Methods: SD and FSL rats were divided into pre-pubertal and pubertal groups, whereafter 14-day saline or SIL treatment was initiated. Pre-pubertal and pubertal rats were treated from postnatal day 21 (PND21) and PND35, respectively. The open field and forced swim tests (FST) were performed on PND60, followed by hippocampal BDNF level analysis one day later. Results: FSL rats displayed greater immobility in the FST compared to SD rats (p < 0.0001), which was reduced by SIL (p < 0.0001), regardless of treatment period. Hippocampal BDNF levels were unaltered by SIL in all treatment groups (p > 0.05). Conclusion: Juvenile sub-chronic SIL treatment reduces the risk of depressive-like behaviour manifesting during young adulthood in genetically susceptible rats.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1838 ◽  
Author(s):  
Yi Zhang ◽  
Ying Zhang ◽  
Xiao-fei Jin ◽  
Xiao-hong Zhou ◽  
Xian-hui Dong ◽  
...  

Background: Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury, and autophagy plays a role in the pathology. Astragaloside IV is a potential neuroprotectant, but its underlying mechanism on cerebral I/R injury needs to be explored. The objective of this study is to investigate the neuroprotective mechanism of Astragaloside IV against cerebral I/R injury. Methods: Middle cerebral artery occlusion method (MCAO) and oxygen and glucose deprivation/reoxygenation (OGD/R) method were used to simulate cerebral I/R injury in Sprague-Dawley (SD) rats and HT22 cells, respectively. The neurological score, 2,3,5-Triphe-nyltetrazolium chloride (TTC) staining, and transmission electron microscope were used to detect cerebral damage in SD rats. Cell viability and cytotoxicity assay were tested in vitro. Fluorescent staining and flow cytometry were applied to detect the level of apoptosis. Western blotting was conducted to examine the expression of proteins associated with autophagy. Results: This study found that Astragaloside IV could decrease the neurological score, reduce the infarct volume in the brain, and alleviate cerebral I/R injury in MCAO rats. Astragaloside IV promoted cell viability and balanced Bcl-2 and Bax expression in vitro, reduced the rate of apoptosis, decreased the expression of P62, and increased the expression of LC3II/LC3I in HT22 cells after OGD/R. Conclusions: These data suggested that Astragaloside IV plays a neuroprotective role by down-regulating apoptosis by promoting the degree of autophagy.


2004 ◽  
Vol 23 (4) ◽  
pp. 239-247 ◽  
Author(s):  
Darryl P. Arfsten ◽  
Eric W. Johnson ◽  
Angie R. Thitoff ◽  
Anne E. Jung ◽  
Erin R. Wilfong ◽  
...  

A number of studies have demonstrated a protective effect associated with N-acetyl-l-cysteine (NAC) against toxic chemical exposure. However, the impact of long-term oral dosing on tissue pathology has not been determined. In this study, the authors assessed the impact of long-term oral NAC administration on organ histopathology and tissue glutathione (GSH) and total glutathione- S-transferase (GST) activity levels in Sprague-Dawley (SD) rats. Groups of 20 SD rats (10 males, 10 females), 8 weeks of age, were dosed daily by oral gavage with deionized H2O (negative controls) or NAC solution at a rate of 600 or 1200 mg/kg/day for 30 days. Animals were euthanized 6 h after treatment on study day 30. There were no significant differences in final body weights or weekly average weight gain between treatment groups. Serum alanine amino-transferase (ALT) activities were significantly elevated ( p ≤.05) in NAC-treated animals compared to controls when measured on study day 30. Histopathologic evaluation of the stomach, small intestine, liver, kidneys, spleen, thymus, and lungs revealed no lesions associated with NAC administration. When measured on study day 30, total GST activity for kidney and skin from NAC-treated animals were increased 39% to 131% as compared to controls. Tissue GSH concentrations from NAC-treated animals were increased 24% to 81% as compared with negative controls. Further studies are needed to determine if the observed increase in tissue GSH concentration and GST activity provide a degree of chemoprotection against dermal and systemic chemical toxicants.


2005 ◽  
Vol 23 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Sherry O. Kasper ◽  
Christy S. Carter ◽  
Carlos M. Ferrario ◽  
Detlev Ganten ◽  
Leon F. Ferder ◽  
...  

Transgenic rats with targeted decreased glial expression of angiotensinogen (ASrAogen rats) did not show an increase in systolic pressure compared with Sprague-Dawley (SD) rats during aging (15–69 wk of age). ASrAogen animals had lower body weights throughout the study, similar to reports for animals with systemic knockout of angiotensinogen or treated long term with renin-angiotensin system (RAS) blockers. Further characterization of indexes of growth and metabolism in ASrAogen rats compared with (mRen2)27 and SD rats, which express elevated versus normal brain and tissue angiotensin II levels, respectively, revealed that serum leptin was 100–200% higher in SD and (mRen2)27 rats at 46 wk and 69 wk of age. Consistent with low serum leptin, ASrAogen rats had higher food intake (73%) compared with SD or (mRen2)27 rats. (mRen2)27 rats had higher resting insulin levels than ASrAogen rats at all ages. Insulin levels were constant during aging in ASrAogen rats, whereas an increase occurred in SD rats, leading to higher insulin levels at 46 and 69 wk of age compared with ASrAogen rats. IGF-1 was comparable among strains at all ages, but (mRen2)27 rats had longer and ASrAogen rats had shorter tail lengths versus SD rats at 15 wk of age. In conclusion, reduced expression of glial angiotensinogen blunts the age-dependent rise in insulin levels and weight gain, findings that mimic the effects of long-term systemic blockade of the RAS or systemic knockout of angiotensinogen. These data implicate glial angiotensinogen in the regulation of body metabolism as well as hormonal mechanisms regulating blood pressure.


2001 ◽  
Vol 281 (2) ◽  
pp. R635-R644 ◽  
Author(s):  
Azeez A. Aileru ◽  
Aline De Albuquerque ◽  
John M. Hamlyn ◽  
Paolo Manunta ◽  
Jui R. Shah ◽  
...  

Altered sympathetic nervous system activity has been implicated often in hypertension. We examined short-term potentiation [posttetanic potentiation (PTP)] and long-term potentiation (LTP) in the isolated superior cervical ganglia (SCG) from Sprague-Dawley (SD) rats given vehicle, digoxin, or ouabain by subcutaneous implants as well as in animals with ouabain-induced hypertension (OHR), and inbred Baltimore ouabain-resistant (BOR) and Baltimore ouabain-sensitive (BOS) strains of rats. Postganglionic compound action potentials (CAP) were used to determine PTP and LTP following a tetanic stimulus (20 Hz, 20 s). Baseline CAP magnitude was greater in ganglia from OHR than in vehicle-treated SD rats before tetanus, but the decay time constant of PTP was significantly decreased in OHR and in rats infused with digoxin that were normotensive. In hypertensive BOS and OHR, the time constants for the decay of both PTP and LTP ( t L) were increased and correlated with blood pressure (slope = 0.15 min/mmHg, r = 0.52, P < 0.047 and 6.7 min/mmHg, r = 0.906, P < 0.0001, respectively). In BOS and OHR, t L (minutes) was 492 ± 40 ( n = 7) and 539 ± 41 ( n = 5), respectively, and differed ( P < 0.05) from BOR (257 ± 48, n = 4), SD vehicle rats (240 ± 18, n = 4), and captopril-treated OHR (370 ± 52, n = 5). After the tetanus, the CAP at 90 min in BOS and OHR SCG declined less rapidly vs. SD vehicle rats or BOR. Captopril normalized blood pressure and t L in OHR. We conclude that the duration of ganglionic LTP and blood pressure are tightly linked in ouabain-dependent hypertension. Our results favor the possibility that enhanced duration of LTP in sympathetic neurons contributes to the increase in sympathetic nerve activity in ouabain-dependent hypertension and suggest that a captopril-sensitive step mediates the link of ouabain with LTP.


Author(s):  
Christianus Rustin ◽  
Zulhabri Othman ◽  
Muhammad Fakhruddin Irfan Bin Sazali

Background and Objective: Heart failure is linked with metabolic syndrome due to an unbalanced dietary intake. Previous studies suggest that cardiac dysfunction is related to chronic inflammation due to injury within the heart muscle. This study focused on the examination and sudden death of Sprague Dawley (SD) rat which was on long-term High-Fat Diet (HFD). The outcomes will potentially provide an insight into future research in sudden death due to HFD. Methods: Total of 15 SD rats grouped into ten HFD and five on normal diet (ND); Female SD rats on HFD underwent physical examination, tissue analysis 12 hours post-death using Hematoxylin & Eosin (H&E) followed by morphological assessment and SD rats from ND used as control. Microscopic images processed using ImageJ and data analysis performed in SPSS software. Results: No significant physical trauma prior to death, however on the 60th day SD rat suffered chronic inflammation to cardiac tissues with Lee Index (LI) of 0.30, indicated the occurrence of Myocardial infarction (MI). The average mean between the size area of inflammation and the region on cardiac tissue is (834.19 ± 103.41) and 94.2% of inflammation activities explained by the four random regions of cardiac tissue (R2= 0.942, F(1, 2)= 32.401, p< 0.05), with every one unit increase in the size area of inflammation, the infected region of cardiac tissue is estimated to increase at 0.970 (?= 0.970, p< 0.05). Conclusion: Chronic inflammation resulted in myocardial injuries led to mortality of SD rats largely due to HFD.


2001 ◽  
Vol 4 (3) ◽  
pp. 175-181 ◽  
Author(s):  
D. D. FULLER ◽  
T. L. BAKER ◽  
M. BEHAN ◽  
G. S. MITCHELL

Long-term facilitation (LTF) is a prolonged, serotonin-dependent augmentation of respiratory motor output following episodic hypoxia. Previous observations lead us to hypothesize that LTF is subject to genetic influences and, as a result, differs between Sprague-Dawley (SD) rats from two vendors, Harlan (H) and Charles River Laboratories/Sasco (CRL/S). Using a blinded experimental design, we recorded integrated phrenic (∫Phr) and hypoglossal neurograms in anesthetized, vagotomized, paralyzed, and ventilated rats. At 60 min following three 5-min hypoxic episodes (PaO2 = 40 ± 1 Torr; 5-min hyperoxic intervals), ∫Phr was elevated from baseline in both SD substrains (i.e., LTF; P < 0.05). Conversely, hypoglossal LTF was present in CRL/S but not H rats ( P < 0.05 between substrains). Serotonin immunoreactivity within the hypoglossal nucleus was not different between H and CRL/S rats. We conclude that the expression of hypoglossal LTF differs between SD rat substrains, indicating a difference in their genetic predisposition to neural plasticity.


2019 ◽  
Vol 47 (7) ◽  
pp. 833-841
Author(s):  
Rebecca R. Moore ◽  
Hiroaki Nagai ◽  
Rodney A. Miller ◽  
Jerry F. Hardisty ◽  
Neil Allison ◽  
...  

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.


2004 ◽  
Vol 4 ◽  
pp. 91-99 ◽  
Author(s):  
Daniela Quaglino ◽  
Miriam Capri ◽  
Luigi Zecca ◽  
Claudio Franceschi ◽  
Ivonne P. Ronchetti

Thymus plays an important role in the immune system and can be modulated by numerous environmental factors, including electromagnetic fields (EMF). The present study has been undertaken with the aim to investigate the role of long-term exposure to extremely low frequency electric and magnetic fields (ELF-EMF) on thymocytes of rats housed in a regular dark/light cycle or under continuous light. Male Sprague-Dawley rats, 2 months old, were exposed or sham exposed for 8 months to 50-Hz sinusoidal EMF at two levels of field strength (1 kV/m, 5 μT and 5 kV/m, 100 μT, respectively). Thymus from adult animals exhibits signs of gradual atrophy mainly due to collagen deposition and fat substitution. This physiological involution may be accelerated by continuous light exposure that induces a massive death of thymocytes. The concurrent exposure to continuous light and to ELF-EMF did not change significantly the rate of mitoses compared to sham-exposed rats, whereas the amount of cell death was significantly increased, also in comparison with animals exposed to EMF in a 12-h dark-light cycle. In conclusion, long-term exposure to ELF-EMF, in animals housed under continuous light, may reinforce the alterations due to a photic stress, suggesting that,in vivo, stress and ELF-EMF exposure can act in synergy determining a more rapid involution of the thymus and might be responsible for an increased susceptibility to the potentially hazardous effects of ELF-EMF.


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