Metabolic Regulatory Clues From the Naked Mole Rat: Toward Brain Regulatory Functions During Stroke

Resistance to tissue hypoxia is a robust fundamental adaptation to low oxygen supply, and represents a novel neuroscience problem with significance to mammalian physiology as well as human health. With the underlying mechanisms strongly conserved in evolution, the ability to resist tissue hypoxia in natural systems has recently emerged as an interesting model in mammalian physiology research to understand mechanisms that can be manipulated for the clinical management of stroke. The extraordinary ability to resist tissue hypoxia by the naked mole rat (NMR) indicates the presence of a unique mechanism that underlies the remarkable healthy life span and exceptional hypoxia resistance. This opens an interesting line of research into understanding the mechanisms employed by the naked mole rat (. Heterocephalus glaber) to protect the brain during hypoxia. In a series of studies, we first examined the presence of neuroprotection in the brain cells of naked mole rats (NMRs) subjected to hypoxic insults, and then characterized the expression of such neuroprotection in a wide range of time intervals. We used oxygen nutrient deprivation (OND), an in vitro model of resistance to tissue hypoxia to determine whether there is evidence of neuronal survival in the hippocampal (CA1) slices of NMRs that are subjected to chronic hypoxia. Hippocampus neurons of NMRs that were kept in hypoxic condition consistently tolerated OND right from the onset time of 5. h. This tolerance was maintained for 24. h. This finding indicates that there is evidence of resistance to tissue hypoxia by CA1 neurons of NMRs. We further examined the effect of hypoxia on metabolic rate in the NMR. Repeated measurement of metabolic rates during exposure of naked mole rats to hypoxia over a constant ambient temperature indicates that hypoxia significantly decreased metabolic rates in the NMR, suggesting that the observed decline in metabolic rate during hypoxia may contribute to the adaptive mechanism used by the NMR to resist tissue hypoxia. This work is aimed to contribute to the understanding of mechanisms of resistance to tissue hypoxia in the NMR as an important life-sustaining process, which can be translated into therapeutic interventions during stroke

Clinical Risk Factors Associated with Ambulatory Outcome in Acute Ischemic Stroke Patient Smokers Treated with Thrombolytic Therapy

Background: Patients who have suffered an acute ischemic stroke (AIS) and are smokers may have a better outcome following thrombolytic therapy when compared with non-smokers. While this finding is controversial, data on baseline clinical risk factors to predict treatment efficacy of thrombolytic therapy using ambulatory status in patients who suffered AIS and are smokers is not common. Methods: Between 2010 and 2016, retrospective data on patients who have suffered an AIS and received recombinant tissue plasminogen activator (rtPA) were obtained from Greenville health system registry. Assessment of clinical risk factors and the likelihood of an improvement in post-stroke ambulation among smokers and non-smokers was carried out using multivariate logistic regression. Results: Of 1001 patients, 70.8% were smokers and 29.2% non-smokers. Among the smokers and non-smokers, 74.6% and 84.6% improvement in ambulation respectively at discharge. The odds of improved ambulation decrease among smokers as age group increases compared to those below 50 [(60–69 years, aOR, 0.30, 95% C.I, 0.108–0.850, p \u3c 0.05), (70–79 years aOR, 0.27, 95% C.I, 0.096–0.734, p \u3c 0.05), (80+ years aOR, 0.16, 95% C.I, 0.057–0.430, P \u3c 0.01). Patients with National Institute of Health Stroke Scale Score (NIHSS) score \u3e 7 (reference \u3c7) were 91% less likely to have improved ambulation among smokers and non-smokers (aOR, 0.09, 95% C.I, 0.055–0.155, P = 0.01), and (aOR, 0.08, 95% C.I, 0.027–0.214, P = 0.01) respectively. Atrial fibrillation was an independent predictor of decreased improvement in ambulation only among smokers (aOR, 0.58, 95% C.I, 0.356–0.928 P \u3c 0.05). Conclusion: Our findings suggest that elderly smokers with atrial fibrillation would benefit more from aggressive management of atrial fibrillation than non-smokers