Abstract TP91: Stroke Induced Respiratory Dysfunction: Age, Apnea and Cognitive Decline

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Anthony Patrizz ◽  
Hilda Ahnstedt ◽  
Louise McCullough
Keyword(s):  
Cognitive Decline ◽  
Minute Ventilation ◽  
Cognitive Outcomes ◽  
Whole Body ◽  
Escape Time ◽  
Cognitive Tests ◽  
Respiratory Dysfunction ◽  
Young Stroke ◽  
Aged Mice ◽  
Post Stroke

Respiratory dysfunction is a common complication of stroke, with an incidence more than 60%, leading to prolonged recovery and increased mortality. Despite the high prevalence of stroke induced respiratory dysfunction (SIRD) little is known regarding how SIRD influences recovery and cognitive outcomes after ischemic stroke. Studies in non-stroke populations have shown that individuals with respiratory dysfunction are drastically more likely to develop cognitive impairment. We propose stroke will induce chronic respiratory dysfunction, instability, and apnea in mice, which are linked to higher mortality and greater post-stroke cognitive deficits. Respiratory dysfunction will be related to progressive cognitive decline following middle cerebral artery occlusion (MCAo) that is worse in aged mice. Whole body plethysmography was performed on C57/B6 young (2-3 month)/aged (20 month) male mice to establish baseline frequency (BPM), tidal volume, minute ventilation and apnea frequency. Animals were exposed to a variety of gas conditions to assess the contribution of peripheral and central chemoreceptors. Mice were subjected to 60 MCAO, producing chronic respiratory dysfunction, instability and apnea, or sham surgery. Days 3, 7 and weekly thereafter plethysmography and a variety of cognitive tests were performed to track respiratory dysfunction and progressive cognitive decline. Young and aged mice displayed hypoventilation (young stroke 181.4±22 vs. sham 264±35 bpm p<.05 and aged stroke 233.7±46.6 bpm vs. sham 369.4±25.9 p<.05) and increased apneas (young stroke 6.8±1.2 vs. 0.8±.8 apnea/min p<.01; aged stroke 16±1 vs. 12±1.5 apneas/min) at day 3 post-stroke. Six weeks later mice were stratified based on # apneas/min into minor (<5 apneas/min N=8) and moderate/severe (>5 apneas/min N=3). Mice with minor apneas perform better in a variety of cognitive tests. Fear conditioning (freezing behavior minor 1.47±.24s/event vs. mod .74±.07s/event, p=.02), Barnes maze: Escape time minor 158.5±35.2 sec vs. 217.9±82. NORT: ratio time novel/familiar object minor 2.2±.6 vs. 1.1±.3. Suggesting incidence of apneas as an indicator of cognitive decline. Therefore, the treatment of respiratory instability is a viable prospect to improve cognitive outcomes.

scholarly journals Reversing Mitochondrial, Metabolic and Molecular Defects in the Brain Improves Cognition in Aged Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 857-858
Author(s):  
Rajagopal Sekhar ◽  
Premranjan Kumar
Keyword(s):  
Oxidative Stress ◽  
Cognitive Decline ◽  
Whole Body ◽  
Cognitively Impaired ◽  
The Novel ◽  
Open Label ◽  
Molecular Defects ◽  
Aged Mice ◽  
Systemic Insulin Resistance ◽  
The Brain

Abstract Age-associated cognitive-decline is a risk factor for Alzheimer’s disease (AD), but mechanisms are not well understood, and interventions are lacking. Rodent studies on AD have not led to therapeutic breakthroughs for cognitively-impaired humans. In an open-label trial in older-adults we found that supplementing GlyNAC (glutathione precursors glycine and N-acetylcysteine) improved cognitive-decline, defects in whole-body mitochondrial-function, and systemic insulin-resistance, oxidative-stress, and inflammation. We hypothesized that aged-mice will have similar defects in the brain, and studied male C57BL/6J mice as follows: young-mice (20w) were compared to two-groups of aged-mice (90-weeks) receiving either GlyNAC or isonitrogenous-placebo diets for 8-weeks. GlyNAC-supplementation improved cognition, and the following measures in the brain: glutathione-concentrations, glucose-transporters in blood-brain-barrier and neurons, mitochondrial glucose-oxidation, oxidative-stress, endoplasmic-reticulum stress, autophagy, mitophagy, inflammation, senescence, genomic and telomere damage. These data provide mechanistic insights into the novel and beneficial role of GlyNAC supplementation to reverse cognitive-decline in aging, and holds promise for human AD.

Skin Cooling on Breath-Hold Duration and Predicted Emergency Air Supply Duration During Immersion

2020 ◽  
Vol 91 (7) ◽  
pp. 578-585
Author(s):  
Victory C. Madu ◽  
Heather Carnahan ◽  
Robert Brown ◽  
Kerri-Ann Ennis ◽  
Kaitlyn S. Tymko ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Hold Time ◽  
Whole Body ◽  
Breath Hold ◽  
Endurance Time ◽  
Skin Exposure ◽  
Breathing Apparatus ◽  
Air Supply ◽  
Skin Cooling ◽  
Breath Hold Duration

PURPOSE: This study was intended to determine the effect of skin cooling on breath-hold duration and predicted emergency air supply duration during immersion.METHODS: While wearing a helicopter transport suit with a dive mask, 12 subjects (29 ± 10 yr, 78 ± 14 kg, 177 ± 7 cm, 2 women) were studied in 8 and 20°C water. Subjects performed a maximum breath-hold, then breathed for 90 s (through a mouthpiece connected to room air) in five skin-exposure conditions. The first trial was out of water for Control (suit zipped, hood on, mask off). Four submersion conditions included exposure of the: Partial Face (hood and mask on); Face (hood on, mask off); Head (hood and mask off); and Whole Body (suit unzipped, hood and mask off).RESULTS: Decreasing temperature and increasing skin exposure reduced breath-hold time (to as low as 10 ± 4 s), generally increased minute ventilation (up to 40 ± 15 L · min−1), and decreased predicted endurance time (PET) of a 55-L helicopter underwater emergency breathing apparatus. In 8°C water, PET decreased from 2 min 39 s (Partial Face) to 1 min 11 s (Whole Body).CONCLUSION: The most significant factor increasing breath-hold and predicted survival time was zipping up the suit. Face masks and suit hoods increased thermal comfort. Therefore, wearing the suits zipped with hoods on and, if possible, donning the dive mask prior to crashing, may increase survivability. The results have important applications for the education and preparation of helicopter occupants. Thermal protective suits and dive masks should be provided.Madu VC, Carnahan H, Brown R, Ennis K-A, Tymko KS, Hurrie DMG, McDonald GK, Cornish SM, Giesbrecht GG. Skin cooling on breath-hold duration and predicted emergency air supply duration during immersion. Aerosp Med Hum Perform. 2020; 91(7):578–585.

Abstract 90: Diabetes Impairs Post-stroke Cerebrovascular Plasticity And Long-term Functional Recovery.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Roshini Prakash ◽  
Weiguo Li ◽  
Zhi Qu ◽  
Susan C Fagan ◽  
Adviye Ergul
Keyword(s):  
Cognitive Decline ◽  
Reperfusion Injury ◽  
Functional Recovery ◽  
Diabetic Rats ◽  
Neurological Deficits ◽  
Ischemic Reperfusion Injury ◽  
Post Stroke ◽  
Ischemic Reperfusion ◽  
Sensorimotor Recovery ◽  
The Impact

Background: Stroke associated with pre-existing diabetes worsens ischemic injury and impairs recovery. We have previously shown that type-2-diabetic rats subjected to cerebral ischemic reperfusion injury develop hemorrhagic transformation (HT) and greater neurological deficits. These diabetic rats also exhibit enhanced dysfunctional cerebral neovascularization that increases the risk of bleeding post-stroke. However, our knowledge of vascular and functional plasticity during the recovery phase of diabetic stroke is limited. This study tested the hypothesis that post-stroke neovascularization is impaired in diabetes and this is associated with poor sensorimotor and cognitive outcomes. Methods: Reparative neovascularization was assessed in the lesional and non-lesional areas in diabetic rats after 14 days of ischemic reperfusion injury. 3-dimensional reconstruction of the FITC stained vasculature were obtained by confocal microscopy and stereological parameters including vascular volume and surface area were measured. Astrogliosis was also determined by GFAP staining. The relative rates of sensorimotor recovery, cognitive decline and spontaneous activity were assessed. Results: Diabetes impairs reparative neovascularization in the lesional areas compared to control rats. Astroglial swelling and reactivity was pronounced in diabetic stroke compared to control stroke. Rate of sensorimotor recovery was significantly slower in diabetic stroke compared to the controls. Diabetes also exacerbated anxiety-like symptoms and cognitive decline post-stroke relative to control. Conclusion: Diabetes impairs post-stroke reparative neovascularization and impedes functional recovery. The impact of glycemic control on poor recovery in this critical period needs to be tested. N=6-8 * p≤ 0.05, ** p≤ 0.005

Abstract W MP50: Pair Housing Reverses the Detrimental Effect of Social Isolation and Restores BDNF and MBP in Aged Mice after Stroke

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rajkumar Verma ◽  
Nia Harris ◽  
Brett Friedler ◽  
Joshua Crapser ◽  
Anita Patel ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Western Blot ◽  
Social Isolation ◽  
Enhanced Recovery ◽  
Infarct Volume ◽  
Recognition Task ◽  
Aged Mice ◽  
Post Stroke ◽  
Beneficial Effects ◽  
Novel Object Recognition Task

Background: Age is an important non-modifiable risk factor for stroke. Stroke rates double every decade after age 55. Social isolation (SI) exacerbates behavioural deficits, slows functional recovery and worsens histological injury after stroke in young animals, primarily by increasing the inflammatory response. However, the inflammatory response differs in aging, and whether the detrimental effects of SI are seen in aged animals is unknown. We hypothesize that acute and chronic post stroke SI will worsen stroke pathology and recovery in aged mice and pair housing (PH) will reverse these effects. Methods: Eighteen-month-old male C57BL/6 mice were pair housed (PH) for two weeks prior to stroke and randomly assigned to various housing conditions immediately after stroke. Behavioral analysis was done weekly starting at day 7. Mice were sacrificed either at 72 hours or 4 weeks after 60-minute right MCAO or sham surgery (n=9-10/group). Results: Mice isolated after stroke (ST-ISO) mice had significantly greater hemispheric infarct volume and neurological deficit scores (p<.05. n=13/group) than pair-housed (PH) stroke mice at 72 hours. SI mice that were isolated immediately after stroke showed significantly higher plasma IL-6 levels compared to PH sham (P<.001, n=13/group ) or PH stroke mice (P<.05) after 72 hour, but levels were similar by 4 weeks post-stroke (n=9-14/group). No change in tissue atrophy was seen after 4 weeks, however a significant interaction [F (1, 28) = 259.6, P<0.001] between housing and stroke was found in the Novel Object Recognition Task (NORT) at day 14. PH led to increased expression of Brain-derived neurotrophic factor (BDNF) and myelin basic protein (MBP) by IHC and western blot (n=5/group for IHC and n= 4/ western blot). Conclusions: Social isolation immediately after stroke led to enhanced injury acutely. Despite similar infarcts at 4 weeks, SI mice had delayed behavioral recovery. Pair housing led to increased expression of BDNF and myelin protein expression. Therefore, the beneficial effects of pair housing may be related to BDNF and MBP expression and enhanced recovery after injury in aged animals.

Post-Stroke Seizures and the Risk of Dementia Among Young Stroke Survivors

2021 ◽  
Author(s):  
Alain Lekoubou ◽  
Djibril M. Ba ◽  
Clever Nguyen ◽  
Guodong Liu ◽  
Douglas L. Leslie ◽  
...  
Keyword(s):  
Stroke Survivors ◽  
Young Stroke ◽  
Post Stroke

Ventilatory behavior after hypoxia in C57BL/6J and A/J mice

2001 ◽  
Vol 91 (5) ◽  
pp. 1962-1970 ◽  
Author(s):  
Fang Han ◽  
Shyam Subramanian ◽  
Thomas E. Dick ◽  
Ismail A. Dreshaj ◽  
Kingman P. Strohl
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
Genetic Effect ◽  
Strain Differences ◽  
Whole Body ◽  
Environmental Forcing ◽  
Ventilatory Responses ◽  
Term Potentiation ◽  
Genetic Mechanisms ◽  
Whole Body Plethysmography

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (V˙e), respiratory frequency (f), tidal volume (Vt), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease inV˙e on reoxygenation with either air (−11%) or 100% O2 (−20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in V˙e (−28.4 vs. −38.7%, air vs. 100% O2) and f (−13.8 vs. −22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase inV˙e (+116%) and f (+62.2%) during air reoxygenation and significant increase in V˙e (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

Homocysteine and cognitive tests as predictors of cognitive decline: A cohort study

2009 ◽  
Vol 283 (1-2) ◽  
pp. 296
Author(s):  
A. Garcia ◽  
A. Hemraj ◽  
S. Klar ◽  
T. Chestney ◽  
L. Khoja ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cognitive Decline ◽  
Cognitive Tests

scholarly journals Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling

2018 ◽  
Vol 128 (5) ◽  
pp. 984-991 ◽  
Author(s):  
Chelsea Angel ◽  
Zachary T. Glovak ◽  
Wateen Alami ◽  
Sara Mihalko ◽  
Josh Price ◽  
...  
Keyword(s):  
Body Weight ◽  
Surgical Stress ◽  
Minute Ventilation ◽  
Whole Body ◽  
Compensatory Response ◽  
Leptin Signaling ◽  
Leptin Receptors ◽  
Congenic Lines ◽  
Increased Risk ◽  
Respiratory Variability

Abstract Background Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing. Methods Mice (n = 40 male and 40 female) comprising four congenic lines that differ in leptin signaling and body weight were injected with saline and buprenorphine (0.3 mg/kg). Whole-body plethysmography was used to quantify the effects on minute ventilation. The data were evaluated using three-way analysis of variance, regression, and Poincaré analyses. Results Relative to B6 mice with normal leptin, buprenorphine decreased minute ventilation in mice with diet-induced obesity (37.2%; P &lt; 0.0001), ob/ob mice that lack leptin (62.6%; P &lt; 0.0001), and db/db mice with dysfunctional leptin receptors (65.9%; P &lt; 0.0001). Poincaré analyses showed that buprenorphine caused a significant (P &lt; 0.0001) collapse in minute ventilation variability that was greatest in mice with leptin dysfunction. There was no significant effect of sex or body weight on minute ventilation. Conclusions The results support the interpretation that leptin status but not body weight or sex contributed to the buprenorphine-induced decrease in minute ventilation. Poincaré plots illustrate that the buprenorphine-induced decrease in minute ventilation variability was greatest in mice with impaired leptin signaling. This is relevant because normal respiratory variability is essential for martialing a compensatory response to ventilatory challenges imposed by disease, obesity, and surgical stress.

scholarly journals UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

2018 ◽  
Vol 46 (4) ◽  
pp. 1683-1692 ◽  
Author(s):  
Hongmei Lang ◽  
Yang Xiang ◽  
Zhihua Ai ◽  
Zhiqing You ◽  
Xiaolan Jin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Dysfunction ◽  
Salt Intake ◽  
Uncoupling Protein ◽  
Left Ventricular ◽  
High Salt ◽  
Whole Body ◽  
Endurance Capacity ◽  
Respiratory Dysfunction

Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH) are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3) plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5%) or a high-salt (HS, 8%) diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Abstract WP153: Post-Stroke Physical Exercise Improves Cognition in Middle-Aged Female Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sharnikha Saravanan ◽  
Weizhao Zhao ◽  
Kunjan R Dave ◽  
Miguel A Perez-Pinzon ◽  
Ami P Raval
Keyword(s):  
Enzyme Activity ◽  
Physical Exercise ◽  
Cognitive Decline ◽  
Fear Conditioning ◽  
Enzyme Activities ◽  
Female Rats ◽  
Male Rats ◽  
Mitochondrial Enzyme ◽  
Post Stroke ◽  
Activity Measurements

Background: A woman’s risk of a stroke increases exponentially following the onset of menopause, andpost-stroke cognitive decline is a significant consequence of stroke survivors. Our earlier study demonstrated that physical exercise (PE) reduced post-stroke brain injury and improved cognitive functions in male rats. The focus of our study is on the improvement of post-stroke cognitive function in female rats. Methods: Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO; 90 min) and randomly assigned to either PE or sham-PE groups. After 3-5 days, rats underwent sham-PE (0m/min speed) or PE (15m/min speed) for 30 mins either every day (continuous) or alternate day for five times on treadmill. The rats that underwent the alternate day paradigm were treated with ER-β agonist (DPN; 1mg/kg) or vehicle-DMSO immediately following PE/sham-PE sessions to determine the synergistic effect. Twenty-one days after the last PE/sham-PE, rats were tested for hippocampal-dependent contextual fear conditioning and freeze time was measured. Rat brains were processed for histology and infarct area was measured with MCID software. From a separate cohort of rat subjected to PE or sham-PE, brain tissue was harvested for various biochemical assays and mitochondrial enzyme activity measurements. Results: Post-tMCAO continuous PE did not reduce ischemic damage. However, alternate PE regimen with or without ER-β agonist reduced infract volume by 20% (p < 0.05) and 23% (p < 0.05), respectively as compared to no-PE. Similarly, alternate PE showed increased freezing on the second day of fear conditioning by 15% (p < 0.05), indicating improved spatial memory. Individual mitochondrial complex I, II, III and IV enzyme activity measurements demonstrated significant improvement in complex III-IV enzyme activities in the alternate PE treated group as compared to sham-PE. Conclusion: An alternate day PE paradigm and ER-β activation improves post-stroke mitochondrial enzyme activities and cognition in reproductively senescent female rats. Future studies delineating underlying mechanism could help identify therapies to prevent/reduce cognitive decline in menopausal female stroke patients.

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