Louise D McCullough

Duke University Medical Center, Durham, North Carolina, United States

Are you Louise D McCullough?

Claim your profile

Publications (101)340.62 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Intracerebral hemorrhage (ICH) is a devastating type of stroke that lacks a specific treatment. An intense immune response develops after ICH, which contributes to neuronal injury, disability, and death. However, the specific mediators of inflammation-induced injury remain unclear. The objective of the present study was to determine whether blood-derived CCR2(+)Ly6C(hi) inflammatory monocytes contribute to disability. ICH was induced in mice and the resulting inflammatory response was quantified using flow cytometry, confocal microscopy, and neurobehavioral testing. Importantly, blood-derived monocytes were distinguished from resident microglia by differential CD45 staining and by using bone marrow chimeras with fluorescent leukocytes. After ICH, blood-derived CCR2(+)Ly6C(hi) inflammatory monocytes trafficked into the brain, outnumbered other leukocytes, and produced tumor necrosis factor. Ccr2(-/-) mice, which have few circulating inflammatory monocytes, exhibited better motor function following ICH than control mice. Chimeric mice with wild-type CNS cells and Ccr2(-/-) hematopoietic cells also exhibited early improvement in motor function, as did wild-type mice after inflammatory monocyte depletion. These findings suggest that blood-derived inflammatory monocytes contribute to acute neurological disability. To determine the translational relevance of our experimental findings, we examined CCL2, the principle ligand for the CCR2 receptor, in ICH patients. Serum samples from 85 patients were collected prospectively at two hospitals. In patients, higher CCL2 levels at 24 h were independently associated with poor functional outcome at day 7 after adjusting for potential confounding variables. Together, these findings suggest that inflammatory monocytes worsen early disability after murine ICH and may represent a therapeutic target for patients.
    Journal of Neuroscience 03/2014; 34(11):3901-9. · 6.91 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Metformin is currently the first-line treatment drug for type 2 diabetes. Metformin is a well-known activator of AMP-activated protein kinase (AMPK). In experimental studies, metformin has been shown to exert direct vascular effects by increasing vascular endothelial growth factor expression and improving microvascular density. As stroke is the leading cause of long-term disability and angiogenesis is implicated as an important mechanism in functional recovery, we hypothesized that chronic metformin treatment would improve post-stroke functional recovery by enhancing functional microvascular density. For this study, C57BL/6N male mice were subjected to a 60-min middle cerebral artery occlusion, and were given 50 mg/kg/day metformin beginning 24 h post-stroke for 3 weeks. Behavioral recovery was assessed using adhesive-tape removal and the apomorphine-induced turning test. The role of angiogenesis was assessed by counting vessel branch points from fluorescein-conjugated lectin-perfused brain sections. Importantly even if metformin treatment was initiated 24 h after injury it enhanced recovery and significantly improved stroke-induced behavioral deficits. This recovery occurred in parallel with enhanced angiogenesis and with restoration of endogenous cerebral dopaminergic tone and revascularization of ischemic tissue. We assessed if the effects on recovery and angiogenesis were mediated by AMPK. When tested in AMPK α-2 knockout mice, we found that metformin treatment did not have the same beneficial effects on recovery and angiogenesis, suggesting that metformin-induced angiogenic effects are mediated by AMPK. The results from this study suggest that metformin mediates post-stroke recovery by enhancing angiogenesis, and these effects are mediated by AMPK signaling.
    European Journal of Neuroscience 03/2014; · 3.75 Impact Factor
  • Fudong Liu, Louise D McCullough
    [show abstract] [hide abstract]
    ABSTRACT: Transient middle cerebral artery occlusion (tMCAO) in rodents is one of the most widely utilized models in experimental stroke studies on focal cerebral ischemia. tMCAO can be modeled in different ways, all aimed at mimicking the clinical scenario of early reperfusion after an ischemic infarct. Some models utilize mechanical occlusion to transiently occlude blood flow with an intraluminal suture, others use "humanized" clot with adjunctive thrombolytic use. This chapter will focus on these two models; the intraluminal suture and thromboembolic MCAO, as they are widely used in stroke research. In addition, several methods of cerebral blood flow (CBF) monitoring during a tMCAO procedure including laser Doppler flowmetry (LDF), laser speckle flowmetry (LSF), and carbon-14 Iodoantipyrine Autoradiography ((14)C-IAP) will be described.
    Methods in molecular biology (Clifton, N.J.) 01/2014; 1135:81-93.
  • Meaghan Roy-O’Reilly, Louise D. McCullough
    [show abstract] [hide abstract]
    ABSTRACT: Stroke is now the leading cause of adult disability in the United States. Women are disproportionately affected by stroke. Women increasingly outnumber men in the elderly population, the period of highest risk for stroke. However, there is also a growing recognition that fundamental sex differences are present that contribute to differential ischemic sensitivity. In addition, gonadal hormone exposure can impact coagulation and fibrinolysis, key factors in the initiation of thrombosis. In this review we will discuss sex differences in stroke, with a focus on platelets, vascular reactivity and coagulation.
    Experimental Neurology 01/2014; · 4.65 Impact Factor
  • V R Venna, Y Xu, S J Doran, A Patrizz, L D McCullough
    [show abstract] [hide abstract]
    ABSTRACT: Stroke survivors often experience social isolation. Social interaction improves quality of life and decreases mortality after stroke. Male mice (20-25 g; C57BL/6N), all initially pair housed, were subjected to middle cerebral artery occlusion (MCAO). Mice were subsequently assigned into one of three housing conditions: (1) Isolated (SI); (2) Paired with their original cage mate who was also subjected to stroke (stroke partner (PH-SP)); or (3) Paired with their original cage mate who underwent sham surgery (healthy partner (PH-HP)). Infarct analysis was performed 72 h after stroke and chronic survival was assessed at day 30. Immediate post-stroke isolation led to a significant increase in infarct size and mortality. Interestingly, mice paired with a healthy partner had significantly lower mortality than mice paired with a stroke partner, despite equivalent infarct damage. To control for changes in infarct size induced by immediate post-stroke isolation, additional cohorts were assessed that remained pair housed for three days after stroke prior to randomization. Levels of brain-derived neurotrophic factor (BDNF) were assessed at 90 days and cell proliferation (in cohorts injected with 5-bromo-2'-deoxyuridine, BrdU) was evaluated at 8 and 90 days after stroke. All mice in the delayed housing protocol had equivalent infarct volumes (SI, PH-HP and PH-SP). Mice paired with a healthy partner showed enhanced behavioral recovery compared with either isolated mice or mice paired with a stroke partner. Behavioral improvements paralleled changes in BDNF levels and neurogenesis. These findings suggest that the social environment has an important role in recovery after ischemic brain injury.
    Translational psychiatry. 01/2014; 4:e351.
  • [show abstract] [hide abstract]
    ABSTRACT: Aging is an important determinant of ischemic stroke outcomes. Both clinical and experimental stroke studies have shown that aging negatively correlates with infarct volumes but is associated with worsened functional recovery after stroke. This may correspond to a differing cellular and molecular response to stroke in the aged versus young brain. It was hypothesized in this study that the smaller injury seen in the aged ischemic brain is because of structural differences in microvasculature with aging or differences in intraischemic tissue perfusion. Both young and aged C57BL6 mice were subject to middle cerebral artery occlusion modeling. Laser speckle flowmetry was used to study the functional dynamics of cerebral perfusion, and fluorescein isothiocyanate (FITC)-dextran staining was performed to examine the structural change in microvasculature. In separate cohorts, cresyl violet staining and immunohistochemistry with CD31 and IgG antibodies were applied to further assess the microvascular density and blood-brain barrier breakdown after stroke. No difference in cerebral blood flow was seen at the baseline, intraischemically, and postreperfusion in young versus aged mice. FITC-dextran and CD31 staining did not show significant differences in the microvascular density between young and aged ischemic brains. More extravasation of IgG through the blood-brain barrier was found in the young versus aged cohort at both 24 and 72 hours after stroke. Cerebrovascular dynamics and perfusion are not responsible for the different stroke phenotypes seen in the young versus aged animals, which may be more related to different levels of blood-brain barrier breakdown.
    Stroke 12/2013; · 6.16 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Social isolation in the pre-stroke environment leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression.
    Behavioural brain research 11/2013; · 3.22 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Despite the high mortality, there is currently no specific treatment for intracerebral hemorrhage (ICH). Research investigating optimum degree of blood pressure control in patients presenting with ICH and hypertension is ongoing. However, there is limited understanding of the potential benefits of specific classes of antihypertensive therapy. β-Adrenergic antagonists may provide neuroprotection from inflammation-induced injury by inhibiting sympathetic nervous system mediated immune activation. We examined mortality in ICH patients receiving β-adrenergic antagonists to determine whether this class of antihypertensive therapy was associated with improved survival. A retrospective analysis of a large, prospectively collected database of patients presenting with acute ICH was performed. Patients were grouped by inpatient β-blocker treatment to determine an effect on mortality during the inpatient stay and at 3months of follow-up. Additional analysis was conducted comparing β-blocker therapy to any other antihypertensive treatment to determine a class-specific association of β-blocker treatment with mortality. The study population included 426 patients with acute, spontaneous ICH. Inpatient β-blocker use was independently associated with decreased rates of inpatient death and mortality at 3months of follow-up. However, univariate and multivariable analyses comparing β-blocker use to other antihypertensives failed to show any class-specific reduction in mortality at either time point. Our study demonstrates that the improvement seen in patients treated with β-adrenergic antagonists is not an effect unique to this class. This supports ongoing trials to determine optimum levels of blood pressure control using multiple classes of antihypertensives.
    Journal of the neurological sciences 10/2013; · 2.32 Impact Factor
  • Arturo Montaño, Ilene Staff, Louise D McCullough, Gil Fortunato
    [show abstract] [hide abstract]
    ABSTRACT: Intravenous (IV) tissue plasminogen activator (tPA) administration for ischemic stroke between 3 and 4.5 hours after onset was found to be safe and beneficial in the ECASS III trial. However, its use has remained controversial, and its benefit as applied in routine practice at community stroke centers is less well defined. This retrospective database study compared safety and clinical outcomes in 500 patients given IV tPA either from 0 to 3 or 3 to 4.5 hours after onset at a high-volume community center from January 2008 to October 2012. Additional independent variables included for univariate and multivariate analysis were age, sex, hypertension, diabetes mellitus, National Institutes of Health stroke scale on arrival. There were no significant differences seen in rates of symptomatic intracranial hemorrhage (3.8% vs 5.8%, P > .05), in-hospital mortality, or Barthel index at 3 months between groups. In addition, tPA administration despite ECASS III contraindications did not appear to be an independent predictor of hemorrhage in the first 24 hours. Our results show that the conclusions of the ECASS III trial can be applied to routine stroke treatment at a community center and that IV thrombolysis in the 3- to 4.5-hour window results in similar safety and efficacy functional outcome at 3 months compared with administration before 3 hours after onset.
    The American journal of emergency medicine 09/2013; · 1.54 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Hypothyroidism is associated with increased ischemic stroke risk but paradoxically results in more favorable outcomes once a stroke occurs. Whether a similar pattern emerges in patients with primary intracerebral hemorrhage (ICH) is unknown. A retrospective analysis of a prospective stroke center database was performed to analyze the clinical presentation and outcomes of hypothyroid patients with spontaneous ICH. Patients were classified into groups with no history of thyroid disease (n = 491) versus those with hypothyroidism (n = 72). Hypothyroid patients were further classified into patients receiving thyroid replacement on admission or those without replacement. The Glasgow Coma Scale, ICH score, and the National Institutes of Health Stroke Scale (NIHSS) were used to assess the initial severity. Outcome was assessed by admission to discharge change in the NIHSS and modified Barthel Index (mBI), in-hospital mortality, discharge disposition and mortality, and the mBI at 3 and 12 months. There were 563 patients in the analysis. Seventy-two patients had a history of hypothyroidism, and of these, 63% received thyroid hormone replacement. Patients receiving replacement had significantly lower NIHSS at presentation (median 4 [IQR 1, 11]) compared with either the control group (median 8 [IQR 3, 16]) or hypothyroid patients without replacement (median 9 [IQR 3.8, 15.5]; P = .004). There was no difference in in-hospital and 3-month mortality or functional outcomes at 3 and 12 months among the groups. This study suggests that the history of hypothyroidism does not affect clinical severity or outcome after ICH.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 09/2013;
  • [show abstract] [hide abstract]
    ABSTRACT: Aging and biological sex are critical determinants of stroke outcome. Post-ischemic inflammatory response strongly contributes to the extent of ischemic brain injury, but how this response changes with age and sex is unknown. We subjected young (5-6months), middle aged (14-15months) and aged (20-22months), C57BL/6 male and female mice to transient middle cerebral artery occlusion (MCAO) and found that a significant age by sex interaction influenced histological stroke outcomes. Acute functional outcomes were worse with aging. Neutrophils, inflammatory macrophages, macrophages, dendritic cells (DCs) and microglia significantly increased in the brain post MCAO. Cycling females had higher Gr1(-) non-inflammatory macrophages and lower T cells in the brain after stroke and these correlated with serum estradiol levels. Estrogen loss in acyclic aged female mice exacerbated stroke induced splenic contraction. Advanced age increased T cells, DCs and microglia at the site of injury, which may be responsible for the exacerbated behavioral deficits in aged. We conclude that aging and sex have differential effects on the post stroke inflammatory milieu. Putative immunomodulatory therapies need to account for this heterogeneity.
    Experimental Neurology 08/2013; · 4.65 Impact Factor
  • Source
    Mehwish A Mirza, Lori Capozzi, Yan Xu, Louise D McCullough, Fudong Liu
    [show abstract] [hide abstract]
    ABSTRACT: Vascular early response gene (Verge) is a novel immediate early gene that is highly expressed during developmental angiogenesis and after ischemic insults in adult brain. However, the role of Verge after neonatal injury is not known. In the present study, we investigated the hypothesis that Verge contributes to vascular remodeling and tissue repair after neonatal ischemic injury. The Rice-Vanucci model (RVM) was employed to induce neonatal stroke in both Verge knockout (KO) and wild-type (WT) postnatal day 10 (P10) mice. Histological and behavioral outcomes at acute (24h), subacute (7d) and chronic (30d) phases were evaluated. Angiogenesis, neurogenesis, and glial scar formation were also examined in the ischemic brain. No significant differences in outcomes were found between WT and Verge mice at 24h or 7 days after stroke. However genetic deletion of Verge led to pronounced cystic cavitation, decreased angiogenensis and glial scar formation in the ischemic hemisphere compared to WT mice at 30 days. Verge knockout mice also had significantly worse functional outcomes at 30 days which was accompanied by decreased neurogenesis and angiogenesis in the ischemic hemisphere. Our study suggests that Verge plays an important role in the induction of neurogenesis and angiogenesis after ischemia, contributes to improved tissue repair, and enhances chronic functional recovery.
    Brain research bulletin 08/2013; · 2.18 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Hyponatremia is a risk factor for stroke and cardiovascular disease. Even mild hyponatremia is associated with increased 30-day mortality after myocardial infarction, and it has recently shown to increase the 3-year mortality after a stroke. In this work, we investigated both acute and chronic clinical outcomes after a stroke in hyponatremic patients. We reviewed all patients admitted between 2004 and 2011 with the diagnosis of acute ischemic stroke. Hyponatremia was defined as serum sodium level less than 135 mmol/L and recorded on admission. All hemorrhagic strokes were excluded. Data were analyzed using multivariate logistic regression. A total of 3585 patients with stroke were identified. Hyponatremia was observed in 565 (16%) patients. Baseline characteristics were similar between groups except heart failure (P = .015), cancer (P = .038), diabetes (P < .001), and dementia (P = .015). Hyponatremic patients had higher National Institutes of Health Stroke Scale (NIHSS) score on admission (P = .032) and at discharge (P = .02). Despite similar modified Barthel Index (mBI) preadmission, patients with hyponatremia had worse mBI on admission (P = .049). Hyponatremia was associated with higher mortality in hospital (P = .039) and at 3-month (P = .001) and 12-month follow-ups (P = .001). A poorer discharge disposition was seen in the hyponatremia group (P = .004). Complications during admission were similar between groups except for urinary infection (P = .008). Patients with hyponatremia had worse NIHSS and mBI values on admission, and their deficits worsened during their hospitalization. This is the first study to demonstrate that hyponatremia is associated with acute mortality and poorer discharge dispositions and to confirm that higher mortality occurs in these patients, even after 12 months after a stroke.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 08/2013;
  • Source
    Fudong Liu, Louise D McCullough
    [show abstract] [hide abstract]
    ABSTRACT: Inflammation plays a critical role in mediating brain injury induced by neonatal hypoxic ischemic encephalopathy (HIE). The mechanisms underlying inflammatory responses to ischemia may be shared by neonatal and adult brains; however, HIE exhibits a unique inflammation phenotype that results from the immaturity of the neonatal immune system. This review will discuss the current knowledge concerning systemic and local inflammatory responses in the acute and subacute stages of HIE. The key components of inflammation, including immune cells, adhesion molecules, cytokines, chemokines and oxidative stress, will be reviewed, and the differences between neonatal and adult inflammatory responses to cerebral ischemic injury will also be discussed.
    Acta Pharmacologica Sinica 07/2013; · 2.35 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Elevation of intracellular calcium was traditionally thought to be detrimental in stroke pathology. However, clinical trials testing treatments that block calcium signaling have failed to improve outcomes in ischemic stroke. Emerging data suggest that calcium may also trigger endogenous protective pathways after stroke. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) is a major kinase activated by rising intracellular calcium. Compelling evidence has suggested that CaMKK and its downstream kinase CaMK IV are critical in neuronal survival when cells are under ischemic stress. We examined the functional role of CaMKK/CaMK IV signaling in stroke. We used a middle cerebral artery occlusion model in mice. Our data demonstrated that pharmacological and genetic inhibition of CaMKK aggravated stroke injury. Additionally, deletion of CaMKK β, one of the 2 CaMKK isoforms, reduced CaMK IV activation, and CaMK IV deletion in mice worsened stroke outcome. Finally, CaMKK β or CaMK IV knockout mice had exacerbated blood-brain barrier disruption evidenced by increased hemorrhagic transformation and activation of matrix metalloproteinase. We observed transcriptional inactivation including reduced levels of histone deacetylase 4 phosphorylation in mice with CaMKK β or CaMK IV deletion after stroke. Our data have established that the CaMKK/CaMK IV pathway is a key endogenous protective mechanism in ischemia. Our results suggest that this pathway serves as an important regulator of blood-brain barrier integrity and transcriptional activation of neuroprotective molecules in stroke.
    Stroke 07/2013; · 6.16 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Intracerebral hemorrhage (ICH) is a severe type of stroke for which there is currently no specific medical therapy. We hypothesized that statins reduce immediate inflammatory injury and improve long-term recovery from increased neurogenesis and angiogenesis. We conducted a large retrospective cohort study to assess the influence of statin therapy on patient death and disability at 12 months after ICH. This was a retrospective analysis of a prospectively collected database at a tertiary care medical center. Patients were grouped based on statin use, and poor outcome was assessed as dead or alive with dependency (modified Barthel Index ≤14). We compared outcomes in 190 patients exposed to statins to 236 patients who were not exposed to statins. Univariate analysis found that statin use was associated with decreased mortality in-hospital and at 12 months (P = .001). Multivariable analysis found that statin use was associated with a decreased odds of death or disability at 12 months after ICH (odds ratio 0.44; 95% confidence interval 0.21-0.95). Statin use is associated with improved long-term outcome at 12 months after ICH. This finding supports previous clinical studies that have shown the short-term benefits of statin therapy. In addition, this study correlates with animal studies supporting the possible long-term recovery benefits of statins.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 07/2013;
  • [show abstract] [hide abstract]
    ABSTRACT: Prolonged dysphagia after middle cerebral artery (MCA) territory strokes may require percutaneous endoscopic gastrostomy (PEG) tube feeding. We examined the predictors of PEG placement among patients with MCA stroke. It was hypothesized that stroke laterality was a predictor. A retrospective cohort study of existing data from Hartford Hospital Stroke Database was done. A total of 157 patients with acute ischemic MCA stroke were included. Patients were divided into the "PEG" group (n = 24) and "no PEG" group (n = 133). Existing demographic, clinical and swallowing data were compared between the 2 groups. Demographic data were similar between the groups. The "PEG" group had a higher admission National Institute of Health Stroke Scale (NIHSS) score, higher proportion of patients who had thrombolytic administration, in- hospital aspiration pneumonia and inability to be assessed on first swallow evaluation. Multivariate analysis revealed that all, except thrombolytic administration may predict PEG placement. Admission NIHSS score, in-hospital aspiration pneumonia and inability to undergo first swallow evaluation may predict PEG placement in patients with acute MCA stroke. Stroke laterality was not associated. This knowledge facilitates early identification of patients that may require PEG tube placement for early nutrition provision and discharge to rehabilitation.
    Neurorehabilitation 07/2013; · 1.42 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Pre-exposure to 3-hydroxy-3-methylgutaryl-coenzyne A reductase inhibitors (statins) appears to improve outcomes in patients with acute ischemic stroke (AIS). Whether this extends to patients over 80 is not known. Patients ≥80 years of age with AIS were retrospectively reviewed from the stroke registry of a tertiary stroke center. Pre-admission statin use, demographics, vascular risk factors, and comorbid conditions were assessed. Primary outcomes were admission National Institutes of Health Stroke Scale (NIHSS) scores and in-hospital mortality/discharge to hospice, and secondary outcomes included subsequent intracerebral hemorrhage (ICH) and modified Barthel index (mBI) at 3 months. Multivariable logistic regression was used to evaluate the association between pre-admission statin use and outcomes among elderly patients. Among 804 patients ≥80, those taking statins prior to AIS admission were overall younger, were more likely to have hypertension, coronary artery disease, diabetes, hyperlipidemia, and were more likely to be on an antiplatelet, but less likely to receive treatment with IV tissue plasminogen activator (tPA). Patients on statin had lower stroke severity (NIHSS>16: 21.9% vs. 27.6%) and in-hospital mortality/discharge to hospice (22.8% vs. 27.6%), but neither was significant. There was no difference in ICH (1.2% vs. 1.9%), and patients on statins had a non-significant trend toward less disability on mBI (27.5% vs. 35.7%). Pre-admission statin use did not show a statistical difference in either outcome, but it did show a trend toward lower stroke severity and improved short-term outcomes. In addition, our study suggests that statins may be safe in elderly stroke patients and may not increase the risk of ICH.
    Archives of gerontology and geriatrics 06/2013; · 1.36 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: BACKGROUND: Middle Cerebral Artery (MCA) territory strokes can be disabling and may leave patients unable to swallow safely. Decisions regarding artificial nutrition and goals of care often arise in patients with severe strokes leading to dysphagia. This study determined some predictors of early transition to palliative level of care among patients with acute ischemic MCA stroke with dysphagia. METHODS: This is a retrospective cohort study. Demographic and clinical data of patients presenting to Hartford Hospital with an acute ischemic stroke between January 2005-December 2010 were gathered utilizing the Stroke Center at Hartford Hospital Database. The 236 patients included were divided into "early transition" and "not transitioned" to palliative care cohorts. Primary outcome was transition to palliative care. Factors that were significantly associated with an early transition to palliative level of care in univariate analysis were then entered into a multivariate logistic regression analysis to identify potential independent predictors of early transition to palliative level of care. The significance level was set at p < 0.05. RESULTS: 79 patients (34%) were transitioned to palliative level of care after failing the first swallow evaluation within a median of 3 days. Factors predictive of an early transition to palliative level of care after multivariate logistic regression analysis included advancing age (p < 0.001; OR: 1.10; 95% CI :1.056-1.155) , left MCA infarct (p = 0.039; OR: 0.417; 95% CI:0.182-0.956), a high NIHSS score on admission (p = 0.017; OR: 3.038; 95% CI: 1.22-7.555), administration of intra-arterial tPA (p < 0.001; OR: 7.106; 955 CI 2.541-19.873) and the inability to be assessed on the 1st swallow evaluation (p < 0.001; OR 0.053; 95% CI 0.022-0.131). CONCLUSIONS: The severity of dysphagia influences early transition to palliative level of care in acute stroke patients. Independent predictors of an early transition to palliative level of care among patients with an acute MCA territory stroke and dysphagia included advancing age, a left MCA infarct, a high NIHSS score on admission, administration of intra-arterial tPA and the inability to be assessed on the 1st swallow evaluation. This information may guide discussions with families of patients with MCA territory strokes regarding artificial nutrition and goals of care.
    BMC Palliative Care 05/2013; 12(1):21. · 1.12 Impact Factor
  • Bharti Manwani, Louise D McCullough
    [show abstract] [hide abstract]
    ABSTRACT: Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved signaling molecule that is emerging as one of the most important energy sensors in the body. AMPK monitors cellular energy status and is activated via phosphorylation when energy stores are low. This allows for maintenance of energy homeostasis by promoting catabolic pathways for ATP production and limiting processes that consume ATP. Growing number of stimuli have been shown to activate AMPK, and AMPK has been implicated in many diverse biological processes, including cell polarity, autophagy, and senescence. The effect of AMPK activation and its biological functions are extremely diverse and depend on both the overall energy "milieu" and the location and duration of activation. AMPK has tissue- and isoform-specific functions in the brain vs. periphery. These functions and the pathways activated also appear to differ by cell location (hypothalamus vs. cortex), cell type (astrocyte vs. neuron), and duration of exposure. Short bursts of AMPK activation have been found to be involved in ischemic preconditioning and neuronal survival; however, prolonged AMPK activity during ischemia leads to neuronal cell death. AMPK may also underlie some of the beneficial effects of hypothermia, a potential therapy for ischemic brain injury. This review discusses the role of AMPK in ischemic stroke, a condition of severe energy depletion. © 2013 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 03/2013; · 2.97 Impact Factor

Publication Stats

2k Citations
66 Downloads
340.62 Total Impact Points

Institutions

  • 2013
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2011–2013
    • National Institutes of Health
      Maryland, United States
    • Saint Francis Hospital And Medical Center, Hartford, Ct
      Hartford, Connecticut, United States
  • 2009–2013
    • University of Connecticut
      • • Department of Neurology
      • • Department of Neuroscience
      Storrs, CT, United States
    • Eastern Virginia Medical School
      • Department of Physical Medicine and Rehabilitation
      Norfolk, VA, United States
  • 2005–2013
    • Hartford Hospital
      • • Department of Neurosurgery
      • • Department of Neurology
      • • Stroke Center
      Hartford, Connecticut, United States
  • 2005–2012
    • UConn Health Center
      • • Department of Neuroscience
      • • Department of Neurology
      Farmington, CT, United States
  • 2010
    • Wannan Medical College
      Wu-hu-shih, Anhui Sheng, China
    • Yale University
      • Department of Neurology
      New Haven, CT, United States
  • 2003–2005
    • Johns Hopkins Medicine
      • • Department of Neurology
      • • Department of Anesthesiology and Critical Care Medicine
      Baltimore, MD, United States
  • 2001
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, MD, United States