Abstract WMP78: Prostaglandin D 2 DP1 Receptor Attenuates the Effects of Post-stroke Sleep Disturbance on Stroke Outcomes

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Abdullah S Ahmad ◽  
Pradip K Kamat ◽  
Damian Hernandez ◽  
Sylvain Dore
Keyword(s):  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Sleep Disturbance ◽  
Treated Group ◽  
Brain Regions ◽  
Cresyl Violet ◽  
Vehicle Group ◽  
Sleep Phase ◽  
Stroke Outcomes ◽  
Post Stroke

Background: Post-stroke sleep disturbance is reported to be an indicator of poor stroke outcomes. The strategic location of the PGD 2 DP1 receptor in specific brain regions regulating cerebrospinal fluid and sleep led us to hypothesize that the DP1 receptor may attenuate the deleterious effects associated with post-stroke sleep disturbance. Methods: First, to test the effect of sleep deprivation on locomotor activity, wildtype mice were individually housed and their activity was monitored 20h/d for 3d. Day zero was used to obtain baseline, while for the next two days, mice were subjected to sleep disturbance for 10h during the sleep phase followed by 10h of no sleep. Second, to test whether a selective DP1 receptor agonist decreases locomotor activity, mice were given an intraperitoneal injection of the agonist and locomotor activity was monitored. Third, to test the effect of post-stroke sleep disturbance on stroke outcomes, wildtype and DP1 -/- mice were subjected to 45min of MCAO and 7d of reperfusion. After MCAO, mice were subjected to post-stroke sleep disturbance for 12h/d for 3d during the mouse sleep phase. Results: Sleep disturbance resulted in higher activity (awake like) during the sleep phase and lower activity during the awake phase. The distance travelled during the awake phase after sleep deprivation was significantly lower (P<0.001). These data suggest that sleep deprivation attenuated locomotor activity. The total ambulatory distance covered by DP1 agonist-treated group 4h post-treatment was 2161.2±846.4cm compared with the vehicle group activity of 7093.5±1953cm (P<0.01), suggesting that the selective pharmacological agent induced sleep. Analysis of the Cresyl violet-stained sections revealed a significantly larger (P<0.05) infarction volume and neurologic deficit in post-stroke, sleep-disturbed DP1 -/- mice compared to similarly treated WT mice. Conclusion: These data show that the PGD 2 DP1 receptor plays a vital role in attenuating the deleterious effects of sleep disturbance on stroke outcomes. Additional studies are underway to further investigate mechanisms and optimal therapeutic conditions. [This work was supported by UF-CTSI (to A.S.A.) and R01NS046400, R01AT007429 (to S.D.)]

scholarly journals Functional recovery after the systemic administration of mesenchymal stem cells in a rat model of neonatal hypoxia-ischemia

2018 ◽  
Vol 22 (5) ◽  
pp. 513-522 ◽  
Author(s):  
Takuro Sakai ◽  
Masanori Sasaki ◽  
Yuko Kataoka-Sasaki ◽  
Shinichi Oka ◽  
Masahito Nakazaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Brain Volume ◽  
Treated Group ◽  
Brain Regions ◽  
Functional Improvement ◽  
Vehicle Group ◽  
Walk Test ◽  
Hypoxia Ischemia

OBJECTIVEChildren who have experienced neonatal hypoxic-ischemic encephalopathy often develop cerebral palsy. Although many treatments have been performed, few effective therapies are available. In this study, the authors tested in rats with hypoxia-ischemia (HI) injuries the hypothesis that the systemic infusion of mesenchymal stem cells (MSCs) would result in functional improvement by facilitating neural compensation in the contralesional cortex.METHODSPostnatal day (P) 7 (P7) rats that had undergone unilateral hemisphere hypoxia-ischemia (modified Rice-Vannucci model) were randomly assigned to MSC-infused or vehicle-infused groups. MSCs (1.0 × 106/200 μL) or vehicle were intravenously infused on P10. Brain volume was measured using in vivo MRI on P8 and P35. On P35, the rats were sacrificed after their behavior was evaluated using a beam walk test, and their brains were then prepared for histological analyses.RESULTSThe MSC-treated group had fewer slips on the beam walk test compared to those in the vehicle group (p = 0.041). MRI was used to measure the volumes of the whole brain, contralesional brain (hemisphere), and residual brain regions of interest, and the results indicated increased brain volume after the intravenous MSC infusions. The histological analyses revealed increased thicknesses of the contralesional cortex and corpus callosum in the MSC group compared with those in the vehicle group (p = 0.021, p = 0.019), which confirmed the volume increases. In the contralesional cortex, the MSC-treated group exhibited significant increases in the numbers of NeuN-positive cells (p = 0.004) and synaptic puncta (p = 0.000) compared with the numbers observed in the vehicle group.CONCLUSIONSThe intravenous infusion of MSCs resulted in improvements in functional outcome, increased brain volume, and enhanced synaptogenesis in HI rats.

scholarly journals Protective effect of Moringa oleifera Lam. leaf extract against carbon tetrachloride-induced neuroinflammation in a mouse model of hepatic encephalopathy

2021 ◽  
Author(s):  
Samah M. Fathy ◽  
Mohammed S.M. Mohammed
Keyword(s):  
Hepatic Encephalopathy ◽  
Carbon Tetrachloride ◽  
Mouse Model ◽  
Experimental Model ◽  
Moringa Oleifera ◽  
Ethanolic Extract ◽  
Treated Group ◽  
Brain Regions ◽  
Primary Response ◽  
Vehicle Group

Abstract Background Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with acute or chronic liver injury. Carbon tetrachloride (CCl4) is usually used as an experimental model for HE. The present study aimed to assess the neuroprotective impacts of Moringa oleifera Lam. leaf ethanolic extract (MOLE) against neurotoxicity in CCl4-induced mouse model of HE. Methods High-performance liquid chromatography (HPLC) analysis was used for the detection of marker compounds; rutin and β-sitosterol. Animals were divided into four groups; vehicle group, CCl4 treated group, MOLE treated group, and (CCl4 + MOLE) group treated with MOLE for 14 days before inducing neurotoxicity by CCl4. Results Pretreatment with MOLE decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), corticosterone, and ammonia levels in serum as well as it improved the antioxidant status of CCl4 treated mice in the tissue of hippocampus (HC) and cerebral cortex (CC). It reduced the expression of toll-like receptor (TLR)4, TLR2, myeloid differentiation primary response 88 (MYD88), and nuclear factor kappa B (NF-κB) genes and the protein levels of the pro-inflammatory cytokines in the selected brain regions. MOLE also exhibited anti-apoptotic effect as revealed by the reduced expression of caspase3, and prevented histological deteriorations caused by CCl4 treatment. Furthermore, CCl4-induced anxiety and depression-like behavioral changes were attenuated by MOLE preadministration. Conclusions Taken together, the current results suggest significant anxiolytic and antidepressant effects of MOLE via modulation of neuroinflammation, oxidative stress, TLR4/2-MyD88/NF-κB pathway, and apoptosis in HE experimental model.

scholarly journals Comparison of age‐dependent alterations in thioredoxin 2 and thioredoxin reductase 2 expressions in hippocampi between mice and rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Yeon Ho Yoo ◽  
Dae Won Kim ◽  
Bai Hui Chen ◽  
Hyejin Sim ◽  
Bora Kim ◽  
...  
Keyword(s):  
Thioredoxin Reductase ◽  
Pyramidal Cells ◽  
Brain Regions ◽  
Young Age ◽  
Cresyl Violet ◽  
Western Blots ◽  
Protein Levels ◽  
Cresyl Violet Staining ◽  
Age Dependent ◽  
The Brain

Abstract Background Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. Results Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. Conclusions Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

Withania somnifera attenuates nicotine induced locomotor sensitization and withdrawal symptoms in mice

2018 ◽  
Vol 7 (2) ◽  
pp. 180-184
Author(s):  
Nitin G Dumore ◽  
◽  
Milind J Umekar ◽  
Brijrsh G Taksande ◽  
Manish M Aglawe ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Withania Somnifera ◽  
Anxiolytic Effect ◽  
Treated Group ◽  
Saline Group ◽  
Nicotine Withdrawal ◽  
Withdrawal Symptoms ◽  
Locomotor Sensitization ◽  
Nicotine Treatment ◽  
Per Se

Objective: To investigate the effect of withania somnifera extract (WSE) on nicotine mediated reinforcement effect and withdrawal symptoms which attributed for the addiction liabilities of nicotine. Methods: In Swiss albino mice nicotine mediated locomotor sensitization and anxiogenic effects of chronic and acute nicotine treatment respectively was tested per se or in combination with WSE. In addition, nicotine withdrawal induced anxiety-like behavior was also studied. Locomotor sensitization was tested by employing open field test (OFT), while symptoms of anxiety were evaluated by subjecting mice to elevated plus maze (EPM). Results: Daily treatment with nicotine (subcutaneous) for 7 days showed gradual increase in the locomotor activity in OFT as compared to saline group indicating the development of locomotor sensitization. Following 3 days of drug free period, nicotine challenge on day 11 also showed rise in locomotor activity depicting expression of sensitization. WSE pretreatment inhibited the nicotine induced development and expression of locomotor sensitization. WSE+nicotine treated group showed decreased ambulations as compared to per se nicotine group on day 1-7 and day 8 (P<0.05). In EPM, acute nicotine treated mice spend more time in open arms as compared to saline indicating the anxiolytic behavior. WSE pretreatment reversed this anxiolytic effect. Nicotine withdrawal mice showed significant increase in the number of entries in arm and total time spend in closed arm indicating anxiety-like behavior. WSE treatment in nicotine withdrawal mice inhibited the nicotine withdrawal induced increased number of entries and time spend in closed arms. Conclusion: These results indicated that WSE may serve an effective herbal medicine in arresting nicotine mediated reinforcement and withdrawal signs

scholarly journals Pills or Sleep Deprivation? Sleep-Deprivation as a Therapeutic Option Intervention in Psychiatry

2020 ◽  
pp. 16-32
Author(s):  
Andrey Viktorovich Antsyborov ◽  
Irina Vladimirovna Dubatova ◽  
Anna Valerievna Kalinchuk
Keyword(s):  
Sleep Deprivation ◽  
Therapeutic Option ◽  
Brain Regions ◽  
Clinical Effects ◽  
Data Set ◽  
Close Supervision ◽  
The Status ◽  
Clinical Conditions ◽  
Traditional Approaches

In recent decades, sleep deprivation has evolved from a single experimental data set to the status of an effective and affordable therapeutic intervention used in daily clinical practice. The mechanism of action of this method is aimed at the same neurotransmitter systems and brain regions as antidepressants. As in the case of pharmacotherapy for sleep deprivation, it should be used under close supervision of a physician. Clinical effects with sleep deprivation are achieved much faster than with psychopharmacotherapy, but they are not long-term in nature. It is possible to improve the results using a combination of pharmacotherapy and sleep deprivation. The use of sleep deprivation in clinical conditions is aimed primarily at preventing depression and its recurrence, as well as in cases resistant to pharmacotherapy. In modern conditions, the method of sleep deprivation is a significant alternative to traditional approaches to therapy of depression.

scholarly journals Racial and ethnic disparities in stroke outcomes: a scoping review of post-stroke disability assessment tools

2018 ◽  
Vol 41 (15) ◽  
pp. 1835-1845 ◽  
Author(s):  
Suzanne Perea Burns ◽  
Brandi M. White ◽  
Gayenell Magwood ◽  
Charles Ellis ◽  
Ayaba Logan ◽  
...  
Keyword(s):  
Scoping Review ◽  
Ethnic Disparities ◽  
Assessment Tools ◽  
Disability Assessment ◽  
Racial And Ethnic Disparities ◽  
Stroke Outcomes ◽  
Post Stroke ◽  
Stroke Disability

Abstract TP101: Intra-arterial IL-1α is Well Tolerated and Neuroprotective After Experimental Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kathleen E Salmeron ◽  
Michael E Maniskas ◽  
Amanda Trout ◽  
Emmanuel Pinteaux ◽  
Justin F Fraser ◽  
...  
Keyword(s):  
Side Effects ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Cresyl Violet ◽  
Current Standard ◽  
Preclinical Research ◽  
Vessel Occlusion ◽  
Post Stroke ◽  
Primary Mouse

Endovascular thrombectomy and t-PA are the only current standard of care treatments for emergent large vessel occlusion (ELVO) stroke. Despite rising recanalization rates, stroke remains the leading cause of long-term disability worldwide suggesting that additional therapies are needed. Severe stroke morbidity may be due, in part, to the acute and sustained inflammatory stroke response. Preclinical research has supported anti-inflammatory agents in limiting brain injury and improving functional outcome; however, the post-stroke inflammatory cascade appears to have both beneficial and deleterious effects, necessitating careful therapeutic translation. We have recently demonstrated that delayed (3 day) post-stroke intravenous (IV) administration of the interleukin (IL)-1α (one of the two major isoforms of the pro-inflammatory family of cytokine IL-1), promoted, rather than suppressed, post-stroke angiogenesis in the transient middle cerebral artery occlusion (MCAo) mouse model. In this study, we aimed to show a therapeutic efficacy of IL-1α in neuroprotection. We investigated the potential for IL-1α, administered acutely IV or intra-arterial (IA) (n=5) after mouse MCAo, to also be neuroprotective. We noted that IV IL-1α (1 ng) is neuroprotective (as measured by cresyl violet stained infarct volumes) with mild, transient side effects (blunted hypertension and bradycardia) that were well tolerated, and with better functional recovery in free motion behavioral tests. IA IL-1α (0.1 ng) administration was even more neuroprotective without the systemic changes seen with IV treatment. Additionally, we noted that IL-1α is directly neuroprotective of primary mouse cortical neurons exposed to oxygen and glucose deprivation conditions in vitro . Taken together, these results suggest that IL-1α could be therapeutic after stroke when administered IV or IA, and the latter may eliminate potentially harmful hemodynamic side effects.

Abstract P422: Chronic Nicotine Exposure Increases Hematoma Growth Following Intracerebral Hemorrhage in Young Rats of Both Sexes

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ashish K Rehni ◽  
Sunjoo Cho ◽  
Hever Navarro Quero ◽  
Miguel A Perez-pinzon ◽  
Ami P Raval ◽  
...  
Keyword(s):  
Treated Group ◽  
Vehicle Group ◽  
Female Group ◽  
Nicotine Exposure ◽  
Hematoma Volume ◽  
Treated Male ◽  
Male Group ◽  
Neurological Score ◽  
Hematoma Growth ◽  
Vehicle Treated Group

Spontaneous intracerebral hemorrhage (sICH) is the deadliest stroke subtype. There is strong evidence that tobacco use / smoking increases the risk of sICH, and some epidemiological studies have observed sex differences in sICH outcomes. However, systematic controlled studies on the effect of tobacco / smoking on post-sICH outcomes in both sexes are lacking. Therefore, we determined the effect of nicotine exposure on outcomes following collagenase-induced sICH both sexes. Young animals of both sexes were randomly divided into nicotine (4.5 mg / kg / day b.w.) and vehicle (saline) treatment groups (using osmotic pumps for two to three weeks). sICH in females was induced during the diestrous stage of estrous cycle. sICH was induced by collagenase injection into the right striatum and ~24 hours later, neurological scores were evaluated, rats were euthanized, and brains were sectioned to measure hematoma volume. Hematoma volumes for male rats was 42% higher (p<0.01) in the nicotine-treated group (139 ± 9 mm 3 , n=10) versus vehicle-treated group (98 ± 9 mm 3 , n=10). Hematoma volumes for female rats was 48% higher (p<0.01) in the nicotine-treated group (134 ± 11 mm 3 , n=10) versus vehicle-treated group (90 ± 7 mm 3 , n=10). Hematoma volumes for the vehicle and nicotine-treated male groups were not different from their respective female groups. The neurological score for the nicotine-treated male group (9.3 ± 0.6) was significantly higher (p<0.05) when compared to vehicle group (7.4 ± 0.6). The neurological score for the nicotine-treated female group (10.7 ± 0.2) was significantly higher (p<0.001) than the vehicle group (7.7 ± 0.7). The neurological score for the vehicle-treated male group was not different from its respective female group. However, the neurological score for the nicotine-treated male group was significantly lower than the female group. Our results show that chronic nicotine exposure increases hematoma volume post-sICH in animals of both sexes. Future studies into the mechanism of nicotine-induced increase in hematoma growth following sICH are required. Support: James and Esther King Biomedical Research Grant 9JK08

Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons

2021 ◽  
Vol 118 (47) ◽  
pp. e2111183118
Author(s):  
Jessica E. Schwarz ◽  
Anna N. King ◽  
Cynthia T. Hsu ◽  
Annika F. Barber ◽  
Amita Sehgal
Keyword(s):  
Locomotor Activity ◽  
Sleep Deprivation ◽  
Circadian Clock ◽  
Sleep Loss ◽  
Daily Cycle ◽  
Shaped Body ◽  
Recovery Sleep ◽  
Sleep Homeostat ◽  
Central Clock ◽  
Homeostatic Mechanisms

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide–dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.

Abstract P746: Sex Differences in Cognitive and Psychological Outcomes of Stroke: Impact of Diabetes

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Victoria L Wolf ◽  
Aunay Miller ◽  
Raghavendar Chandran ◽  
Weiguo Li ◽  
Adviye Ergul
Keyword(s):  
Artery Occlusion ◽  
Psychological Outcomes ◽  
Experimental Stroke ◽  
Dark Light ◽  
Stroke Outcomes ◽  
Post Stroke ◽  
Stroke Research ◽  
Y Maze ◽  
Male Animal ◽  
The Impact

Diabetes increases risk and severity of post-stroke cognitive impairment (PSCI), a major cause of disability worldwide. While it is known that females suffer more from PSCI, psychological outcomes and underlying reasons are poorly understood. From a preclinical perspective, potential explanations include 1) use of otherwise healthy animals in experimental stroke research without integration of common comorbid diseases like diabetes into the study design, and 2) optimization of most behavioral tests for sensorimotor and cognitive functions using only male animal models. Our hypothesis is that post-stroke outcomes are sex and comorbid disease-dependent. To test this, we validated the Novel Object Recognition (NOR), Y-maze, and Passive Avoidance (PAT) behavioral paradigms in Ctrl and Diabetic (DM) male (M) and female (F) rats pre- and post-stroke (S) via 60 min. middle cerebral artery occlusion (MCAO). We tested the PAT paradigm with a multi-trial method where the animals were habituated to the dark/light chambers without foot shock and then trained in 3 trials where they received foot shock upon entering the dark. We then tested retention following MCAO for their memory of foot shock 2 weeks prior. Multitrial results suggested that there was no difference between groups in learning to associate the dark chamber with the shock, so we revised the multitrial method into a single-trial method for ongoing retention tests to compare the impact of stroke on shock memory recall. PAT revealed (Table 1) disease- and sex-dependent responses to aversive stimulus. NOR revealed that M-DM-S and F-DM-S rats have decreased exploration time, suggesting that they are unmotivated or depressed. Y-maze indicated that males displayed spatial memory recovery, while females remained impaired. In summary, we have observed numerous sex- and disease-dependent post-stroke outcomes with standard behavioral paradigms, causing us to carefully consider how we evaluate preclinical outcomes.

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