scholarly journals Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Zidan Zhao ◽  
Rebecca J. Hood ◽  
Lin Kooi Ong ◽  
Giovanni Pietrogrande ◽  
Sonia Sanchez Bezanilla ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Amyloid Beta ◽  
Neuronal Loss ◽  
Treatment Phase ◽  
Experimental Stroke ◽  
Low Oxygen ◽  
Associate Learning ◽  
Atmospheric Air ◽  
Post Stroke ◽  
Cognitive Benefits

Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognized to be notoriously difficult to treat. Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke. There is also emerging evidence that LOPC may improve cognitive function post-stroke. In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke. Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL/6 mice. At 72 h post-stroke animals were randomly assigned to either normal atmospheric air or to one of two low oxygen (11% O2) exposure groups (either 8 or 24 h/day for 14 days). Cognition was assessed during the treatment phase using a touchscreen based paired-associate learning assessment. At the end of treatment (17 days post-stroke) mice were euthanized and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 h) enhanced learning and memory in the 2nd week post-stroke when compared with stroke animals exposed to atmospheric air. Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several vascular deficits, as well as a reduction in the severity of the amyloid-beta (Aβ) burden. These findings provide further insight into the pro-cognitive benefits of LOPC.

scholarly journals Low oxygen post conditioning improves stroke-induced cognitive impairment

2018 ◽  
Author(s):  
Zidan Zhao ◽  
Lin Kooi Ong ◽  
Giovanni Pietrogrande ◽  
Sonia Sanchez Bezanilla ◽  
Kirby Warren ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Learning Task ◽  
Experimental Stroke ◽  
Low Oxygen ◽  
Absolute Level ◽  
Associate Learning ◽  
Air Exposure ◽  
Post Stroke ◽  
Biochemical Analyses

AbstractPost-stroke cognitive impairment has proven to be notoriously difficult to treat. In the current study, we sought to both better understand cellular changes that underpin cognitive deficits and to consider the potential restorative benefits of low oxygen post conditioning (LOPC). We were motivated to use LOPC as an intervention as it is one of the few experimental interventions previously shown to improve cognitive function post-stroke. Experimental stroke was induced by photothrombotic occlusion in adult male C57BL/6 mice. Mice were randomly assigned to either a normal atmospheric air exposure or low oxygen (11% O2) exposure groups three days post-occlusion. On day 17 post-stroke, mice were euthanized for histology or biochemical analyses. Stroked mice exposed to LOPC was associated with marked reductions in amyloid-beta both in its absolute level and in the extent of its oligomerization. Exposure to LOPC post-stroke also improved cellular deficits induced by stroke including an increase in vessel density, a reduction in vascular leakage, and restoration of AQP4 polarisation. Critically, stroked mice exposed to LOPC exhibited robust improvements in cognitive function post-stroke, assessed using a touchscreen based paired- associate learning task. These findings provide compelling pre-clinical evidence of the potential clinical utility of LOPC for enhancing recovery post-stroke.

More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke

2021 ◽  
pp. 0271678X2110058
Author(s):  
Sonia Sanchez-Bezanilla ◽  
Rebecca J Hood ◽  
Lyndsey E Collins-Praino ◽  
Renée J Turner ◽  
Frederick R Walker ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Motor Impairment ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Spatiotemporal Analysis ◽  
Motor Recovery ◽  
Experimental Stroke ◽  
Post Stroke ◽  
Cortical Stroke ◽  
Photothrombotic Stroke

There is emerging evidence suggesting that a cortical stroke can cause delayed and remote hippocampal dysregulation, leading to cognitive impairment. In this study, we aimed to investigate motor and cognitive outcomes after experimental stroke, and their association with secondary neurodegenerative processes. Specifically, we used a photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Motor function was assessed using the cylinder and grid walk tasks. Changes in cognition were assessed using a mouse touchscreen platform. Neuronal loss, gliosis and amyloid-β accumulation were investigated in the peri-infarct and ipsilateral hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed persistent impairment in cognitive function post-stroke, whilst there was a modest spontaneous motor recovery over the investigated period of 84 days. In the peri-infarct region, we detected a reduction in neuronal loss and decreased neuroinflammation over time post-stroke, which potentially explains the spontaneous motor recovery. Conversely, we observed persistent neuronal loss together with concomitant increased neuroinflammation and amyloid-β accumulation in the hippocampus, which likely accounts for the persistent cognitive dysfunction. Our findings indicate that cortical stroke induces secondary neurodegenerative processes in the hippocampus, a region remote from the primary infarct, potentially contributing to the progression of post-stroke cognitive impairment.

scholarly journals Plasma Amyloid Beta and Tau Levels Are Predictors of Post-stroke Cognitive Impairment: A Longitudinal Study

2019 ◽  
Vol 10 ◽  
Author(s):  
Nai-Fang Chi ◽  
Shu-Ping Chao ◽  
Li-Kai Huang ◽  
Lung Chan ◽  
Yih-Ru Chen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Longitudinal Study ◽  
Amyloid Beta ◽  
Post Stroke

scholarly journals Targeting CDK5 post-stroke provides long-term neuroprotection and rescues synaptic plasticity

2016 ◽  
Vol 37 (6) ◽  
pp. 2208-2223 ◽  
Author(s):  
Johanna A Gutiérrez-Vargas ◽  
Herman Moreno ◽  
Gloria P Cardona-Gómez
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Neuronal Loss ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Cyclin Dependent Kinase ◽  
Post Stroke ◽  
Cyclin Dependent Kinase 5

Post-stroke cognitive impairment is a major cause of long-term neurological disability. The prevalence of post-stroke cognitive deficits varies between 20% and 80% depending on brain region, country, and diagnostic criteria. The biochemical mechanisms underlying post-stroke cognitive impairment are not known in detail. Cyclin-dependent kinase 5 is involved in neurodegeneration, and its dysregulation contributes to cognitive disorders and dementia. Here, we administered cyclin-dependent kinase 5-targeting gene therapy to the right hippocampus of ischemic rats after transient right middle cerebral artery occlusion. Cyclin-dependent kinase 5 RNA interference prevented the impairment of reversal learning four months after ischemia as well as neuronal loss, tauopathy, and microglial hyperreactivity. Additionally, cyclin-dependent kinase 5 silencing increased the expression of brain-derived neurotrophic factor in the hippocampus. Furthermore, deficits in hippocampal long-term potentiation produced by excitotoxic stimulation were rescued by pharmacological blockade of cyclin-dependent kinase 5. This recovery was blocked by inhibition of the TRKB receptor. In summary, these findings demonstrate the beneficial impact of cyclin-dependent kinase 5 reduction in preventing long-term post-ischemic neurodegeneration and cognitive impairment as well as the role of brain-derived neurotrophic factor/TRKB in the maintenance of normal synaptic plasticity.

Advances in Studies on Stroke-Induced Secondary Neurodegeneration (SND) and Its Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1154-1168
Author(s):  
Aishika Datta ◽  
Deepaneeta Sarmah ◽  
Kiran Kalia ◽  
Anupom Borah ◽  
Xin Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Motor Function ◽  
Microglial Activation ◽  
Neuronal Loss ◽  
Treatment Modalities ◽  
Treatment Approaches ◽  
Detection Techniques ◽  
Post Stroke ◽  
Function Impairment ◽  
Future Reference

Background: The occurrence of secondary neurodegeneration has exclusively been observed after the first incidence of stroke. In humans and rodents, post-stroke secondary neurodegeneration (SND) is an inevitable event that can lead to progressive neuronal loss at a region distant to initial infarct. SND can lead to cognitive and motor function impairment, finally causing dementia. The exact pathophysiology of the event is yet to be explored. It is seen that the thalami, in particular, are susceptible to cause SND. The reason behind this is because the thalamus functioning as the relay center and is positioned as an interlocked structure with direct synaptic signaling connection with the cortex. As SND proceeds, accumulation of misfolded proteins and microglial activation are seen in the thalamus. This leads to increased neuronal loss and worsening of functional and cognitive impairment. Objective: There is a necessity of specific interventions to prevent post-stroke SND, which are not properly investigated to date owing to sparsely reproducible pre-clinical and clinical data. The basis of this review is to investigate about post-stroke SND and its updated treatment approaches carefully. Methods: Our article presents a detailed survey of advances in studies on stroke-induced secondary neurodegeneration (SND) and its treatment. Results: This article aims to put forward the pathophysiology of SND. We have also tabulated the latest treatment approaches along with different neuroimaging systems that will be helpful for future reference to explore. Conclusion: In this article, we have reviewed the available reports on SND pathophysiology, detection techniques, and possible treatment modalities that have not been attempted to date.

scholarly journals 421 - Mood disorders and its relationship with cognitive impairment and dementia

2020 ◽  
Vol 32 (S1) ◽  
pp. 137-137
Author(s):  
Sandra Torres ◽  
Andreia Lopes
Keyword(s):  
Cognitive Impairment ◽  
Mood Disorders ◽  
Neuronal Loss ◽  
Neurocognitive Impairment ◽  
Attention And Memory ◽  
Psychiatric Illnesses ◽  
Neurocognitive Functions ◽  
The Many ◽  
The One ◽  
Published Research

ABSTRACT:Mood disorders are common psychiatric illnesses that represent a major cause of disability worldwide. With life expectancy and the percentage of elderly people rising in many developed and undeveloped countries around the globe, cognitive impairment and dementia are gaining a societal importance. The relation between mood disorders and cognitive function is a twofold. On the one hand, cognitive deficits within mood disorders have been studied extensively, in which there seems to be a persistent neurocognitive impairment, both in acute phases and in interepisodic euthymic phases. Although results have not always been consistent, an overall pattern of specific impairments – in executive function, attention and memory - has become evident. On the other hand, recent research suggests that mood disorders, in general, may be risk factors for the development of mild cognitive impairment and dementia. In this sense, of the many models for the association of mood disorders and dementia, two are favored by several authors. One suggests that mood disorders are a risk factor for earlier clinical manifestation of dementia. The second sees mood disorders as the cause of dementing states, for instance through neuronal loss via dysregulation of the glucocorticoid cascade. In fact, there is suggestion that impairment of neuroplasticity may underlie the pathophysiology of mood disorders as such, and not only of neurocognitive impairment. In some patients, specific neurocognitive functions may be present before the onset of mood disorder and may constitute a trait factor or even an endophenotype. The aim of the present work is to, through a basic narrative review of published research on the main databases, summarize the main evidences of the association of mood disorders and dementia.

scholarly journals Post-stroke cognitive impairment on the Mini-Mental State Examination primarily relates to left middle cerebral artery infarcts

2021 ◽  
pp. 174749302098455
Author(s):  
Nick A Weaver ◽  
Angelina K Kancheva ◽  
Jae-Sung Lim ◽  
J Matthijs Biesbroek ◽  
Irene MC Huenges Wajer ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cognitive Deficits ◽  
Mini Mental State Examination ◽  
Left Middle Cerebral Artery ◽  
Post Stroke ◽  
Lesion Symptom Mapping ◽  
State Examination ◽  
Left Middle

Background Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods We examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67 ± 12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment. Results Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p < 0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.

Post-stroke Cognitive Impairment and Malnutrition in the Elderly (PCIME): study design and protocol

2021 ◽  
Author(s):  
Zahra Vahabi ◽  
M. Reza Azarpazhooh ◽  
Shima Raeesi ◽  
Shahram Oveisgharan ◽  
Farnaz Etesam ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Study Design ◽  
The Elderly ◽  
Post Stroke
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