Dataset Information

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline.

ABSTRACT:

Background

Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes.

Methods

Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient's serum, at the acute phase of stroke, to determine if they could predict PSCI 3?months later.

Results

We found long-term spatial memory was impaired in diabetic mice 6?weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients.

Conclusions

we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.

SUBMITTER: Cogo A

PROVIDER: S-EPMC7885563 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline.

Cogo Adrien A Mangin Gabrielle G Maïer Benjamin B Callebert Jacques J Mazighi Mikael M Chabriat Hughes H Launay Jean-Marie JM Huberfeld Gilles G Kubis Nathalie N

Molecular neurodegeneration 20210215 1

<h4>Background</h4>Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may em ...[more]

PMID: 33588894

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Project description:BackgroundSex differences in post-stroke cognitive decline have not been systematically evaluated in a nationally representative cohort. We use a quasi-experimental design to investigate sex differences in rate of post-stroke cognitive decline.MethodsUtilizing the event study design, we use the Health and Retirement Study (HRS) data (1996-2016) to evaluate the differences (percentage points [95% Confidence interval]) in the rate of change in cognitive function, measured using the modified version of the Telephone Interview for Cognitive Status (TICS-m) score, before and after incident stroke, and among patients with and without incident stroke. We estimated this event study model for the overall study population and separately fit the same model for male and female participants.ResultsOf 25,872 HRS participants included in our study, 14,459 (55.9%) were females with an overall mean age (SD) of 61.2 (9.3) years. Overall, 2,911 (11.3%) participants reported experiencing incident stroke. Participants with incident stroke (vs. no stroke) had lower baseline TICS-m score (15.6 vs. 16.1). Among participants with incident stroke, the mean pre-stroke TICS-m score was higher than the mean post-stroke TICS-m score (14.9 vs. 12.7). Event study revealed a significant short-term acceleration of cognitive decline for the overall population (4.2 [1.7-6.6] percentage points, p value = 0.001) and among female participants (5.0 [1.7-8.3] percentage points, p value = 0.003). We, however, found no evidence of long-term acceleration of cognitive decline after stroke. Moreover, among males, incident stroke was not associated with significant changes in rate of post-stroke cognitive decline.ConclusionFemales, in contrast to males, experience post-stroke cognitive deficits, particularly during early post-stroke period. Identifying the sex-specific stroke characteristics contributing to differences in post stroke cognitive decline may inform future strategies for reducing the burden of post-stroke cognitive impairment and dementia.

Project description:Cognitive decline is a major cause of disability in stroke survivors. The magnitude of survivors' cognitive changes after stroke is uncertain.To measure changes in cognitive function among survivors of incident stroke, controlling for their prestroke cognitive trajectories.Prospective study of 23,572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, residing in the continental United States, enrolled 2003-2007 and followed up through March 31, 2013. Over a median follow-up of 6.1 years (interquartile range, 5.0-7.1 years), 515 participants survived expert-adjudicated incident stroke and 23,057 remained stroke free.Time-dependent incident stroke.The primary outcome was change in global cognition (Six-Item Screener [SIS], range, 0-6). Secondary outcomes were change in new learning (Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; range, 0-30), verbal memory (Word-List Delayed Recall; range, 0-10), and executive function (Animal Fluency Test; range, ?0), and cognitive impairment (SIS score <5 [impaired] vs ?5 [unimpaired]). For all tests, higher scores indicate better performance.Stroke was associated with acute decline in global cognition (0.10 points [95% CI, 0.04 to 0.17]), new learning (1.80 points [95% CI, 0.73 to 2.86]), and verbal memory (0.60 points [95% CI, 0.13 to 1.07]). Participants with stroke, compared with those without stroke, demonstrated faster declines in global cognition (0.06 points per year faster [95% CI, 0.03 to 0.08]) and executive function (0.63 points per year faster [95% CI, 0.12 to 1.15]), but not in new learning and verbal memory, compared with prestroke slopes. Among survivors, the difference in risk of cognitive impairment acutely after stroke, compared with immediately before stroke, was not statistically significant (odds ratio, 1.32 [95% CI, 0.95 to 1.83]; P?=?.10); however, there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate (odds ratio, 1.23 per year [95% CI, 1.10 to 1.38]; P?<?.001). For a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference of 4.0% (95% CI, -1.2% to 9.2%) at year 3 and 12.4% (95% CI, 7.7% to 17.1%) at year 6.Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years.

Dataset Information

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline.

Background

Methods

Results

Conclusions

Publications

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline.

Similar Datasets

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