Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline

Assayag, Einor Ben; Eldor, Roy; Korczyn, Amos D.; Kliper, Efrat; Shenhar‐Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M.; Auriel, Eitan

doi:10.1161/strokeaha.117.017709

Cited by 50 publications

(44 citation statements)

References 26 publications

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“…The third independent variable associated with WMH progression was GFR, with lower GFR values in WHM progressors. The finding that patients with impaired renal function have an increased WMH burden has been reported in several cross-sectional studies both in subjects with cardiovascular risk factors [35,36], and patients with previous stroke [37,38]. Nevertheless, this is the first longitudinal study in patients with a carotid plaque showing a significant association between renal impairment and risk of WMH progression.…”

Section: Discussionsupporting

confidence: 50%

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization

et al. 2019

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Section: Discussionsupporting

confidence: 50%

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization

et al. 2019

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“…This model also did not exacerbate white matter injury after stroke. The disruption of white matter integrity in the uninjured brain of T2D patients has been recently shown [59]. However, whether it is exacerbated after stroke in T2D patients is still largely undetermined [60,61].…”

Section: Discussionmentioning

confidence: 99%

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

et al. 2019

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Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain’s self-repair mechanisms – stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet (HFD) and subjected to transient middle cerebral artery occlusion (tMCAO). We evaluated neurological recovery by upper-limb grip strength at 1 and 6 weeks after tMCAO. Gray and white matter damage, stroke-induced neurogenesis, and survival and potential atrophy of PV-interneurons were quantitated by immunohistochemistry (IHC) at 2 and 6 weeks after tMCAO. Obesity/T2D impaired neurological function without exacerbating brain damage. Moreover, obesity/T2D diminished stroke-induced neural stem cell (NSC) proliferation and neuroblast formation in striatum and hippocampus at 2 weeks after tMCAO and abolished stroke-induced neurogenesis in hippocampus at 6 weeks. Finally, stroke resulted in the atrophy of surviving PV-interneurons 2 weeks after stroke in both non-diabetic and obese/T2D mice. However, after 6 weeks, this effect selectively persisted in obese/T2D mice. We show in a preclinical setting of clinical relevance that obesity/T2D impairs neurological functions in the stroke recovery phase in correlation with reduced neurogenesis and persistent atrophy of PV-interneurons, suggesting impaired neuroplasticity. These findings shed light on the mechanisms behind impaired stroke recovery in T2D and could facilitate the development of new stroke rehabilitative strategies for obese/T2D patients.

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“…Interestingly, the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study examined a combination of genetic, inflammatory, imaging, and psychological markers during the acute phase to predict longterm cognitive and functional decline, with collection of both blood and saliva [61]. While TABASCO identified imaging abnormalities, motor function (i.e., balance, gait), and comorbidities as biomarkers for cognitive decline [45,62,63], blood and saliva results have yet to be published.…”

Section: Current Biomarker Trials For Strokementioning

confidence: 99%

Biomarker Application for Precision Medicine in Stroke

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Janowski

et al. 2019

Transl. Stroke Res.

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Stroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies can be designed to support precision medicine therapeutic interventions after stroke. The current challenges in defining ideal biomarkers for stroke are highlighted, including consideration of disease course, age, lifestyle factors, and subtypes of stroke. This overview of current clinical trials includes biomarker collection, and concludes with an example of biomarker design for aneurysmal subarachnoid hemorrhage. With the advent of "-omics" studies, neuroimaging, big data, and precision medicine, well-designed stroke biomarker trials will greatly advance the treatment of a disease that affects millions globally every year.

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Type 2 Diabetes Mellitus and Impaired Renal Function Are Associated With Brain Alterations and Poststroke Cognitive Decline

Abstract: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691.

Cited by 50 publications

References 26 publications

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

Biomarker Application for Precision Medicine in Stroke

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