scholarly journals Poststroke cognitive impairment and hippocampal neurovascular remodeling: the impact of diabetes and sex

2018 ◽  
Vol 315 (5) ◽  
pp. H1402-H1413 ◽  
Author(s):  
Rebecca Ward ◽  
John Paul Valenzuela ◽  
Weiguo Li ◽  
Guangkuo Dong ◽  
Susan C. Fagan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Microglial Activation ◽  
Neuronal Degeneration ◽  
Artery Occlusion ◽  
Cognitive Outcomes ◽  
Stroke Severity ◽  
Male And Female ◽  
Neuronal Density ◽  
Neurovascular Remodeling ◽  
The Impact

Diabetes increases the risk and severity of cognitive impairment, especially after ischemic stroke. Pathological remodeling of the cerebrovasculature has been postulated to contribute to poor neuronal repair and worsened cognitive deficits in diabetes. However, little is known about the effect of diabetes on the vascularization of hippocampus, a domain critical to memory and learning. Therefore, we had two aims for this study: 1) to determine the impact of diabetes on hippocampal neurovascular remodeling and the resulting cognitive impairment after stroke using two models with varying disease severity, and 2) to compare the effects of ischemia on hippocampal neurovascular injury in diabetic male and female animals. Stroke was induced by middle cerebral artery occlusion (MCAO) by either the suture or embolic method in control and diabetic age-matched male and female Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial activation as well as cognitive outcomes were measured. Embolic MCAO induced greater neuronal degeneration, pathological vascularization, microglial activation, and cognitive impairment in diabetes as compared with control animals or 60-min MCAO. Although diabetic males had lower neuronal density at baseline, diabetic females had more neurodegeneration after stroke. Control animals recovered cognitive function by day 14 after stroke; diabetic animals showed deficits regardless of sex. These results suggest that mechanisms underlying cognitive decline in diabetes may differ in males and females and provide further insight to the impact of diabetes on stroke severity and poststroke cognitive impairment. NEW & NOTEWORTHY The present study is the first to provide comparative information on the effects of diabetes and ischemia on cognitive outcomes in both sexes while also evaluating the neurovascular structure in the hippocampus, a critical region for cognitive and memory-related tasks.

Abstract WP492: Differential Effects of Iron Chelation With Deferoxamine on Post-Stroke Neurovascular Inflammation: Disease and Sex Interactions

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Victoria L Wolf ◽  
Weiguo Li ◽  
Yasir Abdul ◽  
Guangkuo Dong ◽  
Rebecca Ward ◽  
...  
Keyword(s):  
Functional Outcomes ◽  
Microglial Activation ◽  
Iron Chelation ◽  
Artery Occlusion ◽  
Significant Loss ◽  
Cognitive Outcomes ◽  
Mesenchymal Transition ◽  
Differential Effects ◽  
Post Stroke ◽  
Neurovascular Remodeling

We have shown that 1) poor recovery in diabetes is associated with greater hemorrhagic transformation and significant loss of the cerebrovasculature, and 2) iron chelation therapy with deferoxamine (DFX) improves sensorimotor and cognitive outcomes while preventing vasoregression in male diabetic animals after stroke. This study tested the hypotheses that 1) diabetes mediates pathological post-stroke neovascularization in females and 2) DFX attenuates microglial activation and pathological neurovascular remodeling in both sexes. Control and diabetic animals were subjected to embolic middle cerebral artery occlusion (MCAO). DFX (100 mg/kg) or vehicle was given 1hour after MCAO and repeated every 12h for 7 days after stroke. Functional outcomes were assessed over time. Vascular indices, microglial morphology (activation), and neurovascular integrity (IgG and unpolarized Aquaporin-4) were measured at Day 14. Male and female microvascular endothelial cells (BMVECs) treated with iron and/or DFX were tested for viability and endothelial mesenchymal transition (EndMT) markers. DFX preserved vascular volume post-stroke in diabetic males. Stroke did not cause vasoregression in diabetic female animals; however, DFX reduced vascular indices while improving sensorimotor but not cognitive outcomes in both control and diabetic females. Ischemic injury amplified microglial activation and neurovascular remodeling in diabetes while DFX treatment restored these changes to control levels in male diabetic animals but not in females (Table). Female BMVECs grown under diabetic conditions expressed α-SMA and N-cadherin while VE-cadherin was decreased, indicative of EndMT (p<0.05 vs normal glucose). Data suggest that DFX treatment has sex- and disease-dependent effects on post-stroke neovascularization. Additional studies will aim to address the mechanisms by which DFX exerts these differential effects on functional outcomes and neurovascular remodeling.

scholarly journals Chronic Cerebral Hypoperfusion Induces Vascular Plasticity and Hemodynamics but Also Neuronal Degeneration and Cognitive Impairment

2015 ◽  
Vol 35 (8) ◽  
pp. 1249-1259 ◽  
Author(s):  
Zhen Jing ◽  
Changzheng Shi ◽  
Lihui Zhu ◽  
Yonghui Xiang ◽  
Peihao Chen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Neuronal Degeneration ◽  
Neuronal Loss ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Common Carotid Artery Occlusion

Chronic cerebral hypoperfusion (CCH) induces cognitive impairment, but the compensative mechanism of cerebral blood flow (CBF) is not fully understood. The present study mainly investigated dynamic changes in CBF, angiogenesis, and cellular pathology in the cortex, the striatum, and the cerebellum, and also studied cognitive impairment of rats induced by bilateral common carotid artery occlusion (BCCAO). Magnetic resonance imaging (MRI) techniques, immunochemistry, and Morris water maze were employed to the study. The CBF of the cortex, striatum, and cerebellum dramatically decreased after right common carotid artery occlusion (RCCAO), and remained lower level at 2 weeks after BCCAO. It returned to the sham level from 3 to 6 weeks companied by the dilation of vertebral arteries after BCCAO. The number of microvessels declined at 2, 3, and 4 weeks but increased at 6 weeks after BCCAO. Neuronal degeneration occurred in the cortex and striatum from 2 to 6 weeks, but the number of glial cells dramatically increased at 4 weeks after BCCAO. Cognitive impairment of ischemic rats was directly related to ischemic duration. Our results suggest that CCH induces a compensative mechanism attempting to maintain optimal CBF to the brain. However, this limited compensation cannot prevent neuronal loss and cognitive impairment after permanent ischemia.

Abstract TMP45: Predicting Long-term Body Function, Activity & Participation After Stroke: The Prevailing Role of Cognition in Determining Functional Outcome

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Arunima Kapoor ◽  
Krista Lanctot ◽  
Mark Bayley ◽  
Alex Kiss ◽  
Richard Swartz
Keyword(s):  
Cognitive Impairment ◽  
Functional Outcome ◽  
Stroke Severity ◽  
Post Stroke ◽  
Body Function ◽  
Multiple Levels ◽  
Multiple Domains ◽  
Levels Of Functioning ◽  
The Impact

Background: Stroke can impact multiple levels of function and result in complex disability. Few studies have examined limitations across the range of functions from body function to social participation, or explored the impact of post-stroke comorbidities, such as depression, obstructive sleep apnea (OSA) and cognition, on function, especially in the long-term. We aimed to determine post-stroke predictors of multiple levels of functioning approximately 2 years after a stroke, and to specifically evaluate the impact of depressive symptoms, OSA and cognitive impairment on outcome. Hypothesis: We hypothesized that in addition to traditional predictors of outcome–age and stroke severity–depression, OSA and cognitive impairment will predict functional outcome in multiple domains. Methods: Baseline assessment of depression, apnea and cognitive impairment with 2-year follow-up assessment of functional outcome to evaluate each of the three levels of functioning as stated in the WHO International Classification of Functioning: Body Function (Montreal Cognitive Assessment), Activity (modified Rankin) and Participation (Reintegration to Normal Living Index). Results: A total of 162 patients were enrolled at approximately 2 years and 5 months post-stroke. Forty one percent had activity limitations, 58% were cognitively impaired and 68% had restrictions in participation. Long-term activity limitation was predicted by greater age (OR = 0.95), stroke severity (OR = 1.69) and cognitive impairment (OR = 1.28) at baseline. Body function impairment was predicted by greater age (OR = 0.96), and cognitive impairment (OR = 1.49). Participation restriction was predicted by cognitive impairment (OR = 1.26). Conclusion: Baseline cognition predicts long-term function in multiple domains and is a better predictor of long-term participation than age or baseline stroke severity. In view of the widespread impact of post-stroke cognitive impairment on every level of functioning, routine post-stroke cognitive screening and target interventions are warranted. Greater attention to functional domains beyond activity could further optimize recovery and enhance outcome after stroke.

scholarly journals Pathways linking late-life depression to persistent cognitive impairment and dementia

2008 ◽  
Vol 10 (3) ◽  
pp. 345-357 ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Clinical Status ◽  
Late Life ◽  
Cognitive Outcomes ◽  
Late Life Depression ◽  
Increased Risk ◽  
The Impact

There is a strong association between late-life depression, cognitive impairment, cerebrovascular disease, and poor cognitive outcomes, including progressive dementia, especially Alzheimer's disease. While neuroimaging evidence suggests that cerebrovascular disease plays a prominent role, it seems that depression alone may also confer substantial risk for developing Alzheimer's disease. The relationships between the prominent cerebrovascular changes, other structural abnormalities, specific forms of cognitive dysfunction, and increased risk for developing Alzheimer's disease among those with late-life depression have been difficult to reconcile. The varied findings suggest that there are likely multiple pathways to poor cognitive outcomes. We present a framework outlining multiple, non-mutually exclusive etiologic links between depression, cognitive impairment, and progressive decline, including dementia. Importantly, the model is both testable and falsifiable. Going forward, using models such as this to inform research should accelerate knowledge acquisition on the depression/dementia relationship that may be useful for dementia prevention, monitoring the impact of depression treatment on clinical status and course of illness.

scholarly journals High Neutrophil–Lymphocyte Ratio Predicts Post-stroke Cognitive Impairment in Acute Ischemic Stroke Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Minwoo Lee ◽  
Jae-Sung Lim ◽  
Chul-Ho Kim ◽  
Sang-Hwa Lee ◽  
Yerim Kim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Systemic Inflammation ◽  
Cognitive Outcomes ◽  
Stroke Patients ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Post Stroke ◽  
Increased Risk ◽  
The Impact

Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke.Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of &lt; -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type.Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1–4] and 2.26 [1.65–2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00–1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17–9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains.Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.

The Impact of a Comorbid Spinal Cord Injury on Cognitive Outcomes of Male and Female Patients with Traumatic Brain Injury

PM&R ◽  
2020 ◽  
Author(s):  
Tatyana Mollayeva ◽  
Mitchel Sutton ◽  
Michael Escobar ◽  
Mackenzie Hurst ◽  
Angela Colantonio
Keyword(s):  
Traumatic Brain Injury ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Brain Injury ◽  
Cognitive Outcomes ◽  
Male And Female ◽  
Female Patients ◽  
Cord Injury ◽  
The Impact

The Impact of Timing of Microglial Activation by Inflammation and Hypoxia Regarding Additive Neurotoxic Effects

2014 ◽  
Vol 45 (S 01) ◽  
Author(s):  
S. Jung ◽  
D. Frey ◽  
F. Brackmann ◽  
M. Richter-Kraus ◽  
R. Trollmann
Keyword(s):  
Microglial Activation ◽  
Neurotoxic Effects ◽  
The Impact

Exogenous Neonatal Erythropoietin Mitigates Brain Damage After a Combination of Prenatal Hypoxic-Ischemia and Lipopolysaccharide Inflammation in Rats

2008 ◽  
Vol 1 (4) ◽  
pp. A353
Author(s):  
Shenandoah Robinson ◽  
Qing Li
Keyword(s):  
Brain Damage ◽  
Intracellular Signaling ◽  
System Development ◽  
Intrauterine Infection ◽  
Artery Occlusion ◽  
Nervous System Development ◽  
Human Infants ◽  
Hypoxic Ischemia ◽  
Show Evidence ◽  
The Impact

Introduction Many infants born very preterm who suffer brain damage most likely experienced a combined insult from intrauterine infection and placental insufficiency. Damage is thought to be synergistic rather than additive but the mechanisms of combined injury remain elusive. A combination of lipopolysaccharide-induced inflammation and hypoxia-ischemia has been used in rats to model the dual insult that occurs in human infants prenatally. Erythropoietin, a pleiotrophic cytokine that is essential for central nervous system development, ameliorates brain injury after isolated hypoxic-ischemic or inflammatory insults through different intracellular signaling pathways. We hypothesized that exogenous neonatal EPO administration would lessen the damage of a combined prenatal insult in rats. Methods On embryonic Day 18 fetal rats experienced 60 minutes of transient uterine artery occlusion with or without intracervical LPS administration with sham controls receiving surgery but no occlusion and saline for LPS. Survival was recorded and histological biochemical and functional assays were performed. Means were compared with ANOVA with Tukey HSD post hoc analysis. Results After a combined insult of HI and 0.15-mg/kg LPS on E18 the survival of pups by postnatal Day 1 (P1) decreased from 77% with HI alone to 22% for LPS plus HI. When exogenous systemic EPO was administered P1–P3 survival to P9 improved markedly from 40% (2 of 5) for saline-treated insult pups to 100% (6 of 6) for EPO-treated. Initial histological analyses show EPO decreases the number of brain activated caspase 3 and activated microglia by P9. Additional analyses will be presented. Conclusion As at least 60% of placentas from infants born pre-term show evidence of chorioamnionitis, assessment of the impact of exogenous EPO on a model of a combination injury is essential prior to proceeding with a clinical trial. Initial results indicate neonatal exogenous EPO mitigates damage from the combined insult.

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