Diabetic aggravation of stroke and animal models

Rehni, Ashish K.; Liu, Allen; Pérez-Pinzón, Miguel A.

doi:10.1016/j.expneurol.2017.03.004

Cited by 23 publications

(15 citation statements)

References 352 publications

(439 reference statements)

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“…Second, a single administration of streptozotocin damages pancreatic β‐cells and is a simple, cost effective and established method for inducing hyperglycaemia in type 1 diabetes. Regarding cerebral ischaemia, the endovascular MCAO is the most used model by far because it represents 82% of the focal cerebral ischaemia models employed in diabetes experiments . Third, we followed a previously described protocol that allowed reaching optimal and sustained plasma concentrations of BZA (20.7 ± 2.1 ng mL ‐1 ) or E 2 (45.6 ± 7.8 pg mL ‐1 ) from 4 hours after the onset of ischaemia until the end of the procedure (24 hours).…”

Section: Discussionmentioning

confidence: 99%

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

Burguete

Jover‐Mengual

López‐Morales

et al. 2019

J Neuroendocrinology

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Because neuroprotection in stroke should be revisited in the era of recanalisation, the present study analysed the potential neuroprotective effect of the selective oestrogen receptor modulator, bazedoxifene acetate (BZA), in an animal model of diabetic ischaemic stroke that mimics thrombectomy combined with adjuvant administration of a putative neuroprotectant. Four weeks after induction of diabetes (40 mg kg -1 streptozotocin, i.p.), male Wistar rats were subjected to transient middle cerebral artery occlusion (intraluminal thread technique, 60 minutes) and assigned to one of three groups treated with either: vehicle, BZA (3 mg kg -1 day -1 , i.p.) or 17β-oestradiol (E 2 ) (100 μg kg -1 day -1 , i.p.). At 24 hours post-ischaemia-reperfusion, brain damage (neurofunctional score, infarct size and apoptosis), expression of oestrogen receptors (ER)α, ERβ and G protein-coupled oestrogen receptor), and activity of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)1/2 and phosphoinositide 3-kinase/Akt pathways were analysed. At 24 hours after the ischaemic insult, both BZA-and E 2 -treated animals showed lower brain damage in terms of improved neurofunctional condition, decreased infarct size and decreased apoptotic cell death.Ischaemia-reperfusion induced a significant decrease in ERα and ERβ expression without affecting that of G protein-coupled oestrogen receptor, whereas BZA and E 2 reversed such a decrease. The ischaemic insult up-regulated the activity of both the MAPK/ERK1/2 and phosphoinositide 3-kinase/Akt pathways; BZA and E 2 attenuated the increased activity of the ERK1/2 pathway, without affecting that of the Akt pathway. The results of the present study lend further support to the consideration of BZA as an effective and safer alternative overcoming the drawbacks of E 2 with respect to improving diabetic ischaemic stroke outcome after successful reperfusion. K E Y W O R D S 17β-oestradiol, apoptosis, bazedoxifene, diabetes, ischaemic stroke, selective oestrogen receptor modulators How to cite this article: Burguete MC, Jover-Mengual T, López-Morales MA, et al. The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β-oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway. J Neuroendocrinol. 2019;31:e12751.

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Section: Discussionmentioning

confidence: 99%

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

Burguete

Jover‐Mengual

López‐Morales

et al. 2019

J Neuroendocrinology

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“…For example, neurological impairment and recovery after experimental stroke is often worse in older animals compared with their younger counterparts 27 28. Hypertension and diabetes are very common in the elderly and both have been shown to worsen outcome in experimental stroke models 27 29. Obesity also worsens outcome after experimental stroke, with more ischaemic damage and greater blood–brain barrier breakdown observed in obese rodents compared with controls 30–33.…”

Section: Why Should We Consider Comorbidities?mentioning

confidence: 99%

Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

McCann¹,

Lawrence²

2020

BMJ Open Science

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Stroke is a significant cause of mortality and morbidity for which there are limited treatment options. Virtually all drug interventions that have been successful preclinically in experimental stroke have failed to translate to an effective treatment in the clinical setting. In this review, we examine one of the factors likely contributing to this lack of translation, the failure of preclinical studies to consider fully the advanced age and comorbidities (eg, hypertension or diabetes) present in most patients with stroke. Age and comorbidities affect the likelihood of suffering a stroke, disease progression and the response to treatment. Analysing data from preclinical systematic reviews of interventions for ischaemic stroke we show that only 11.4% of studies included an aged or comorbid model, with hypertension being the most frequent. The degree of protection (% reduction in infarct volume) varied depending on the comorbidity and the type of intervention. We consider reasons for the lack of attention to comorbid and aged animals in stroke research and discuss the value of testing a potential therapy in models representing a range of comorbidities that affect patients with stroke. These models can help establish any limits to a treatment’s efficacy and inform the design of clinical trials in appropriate patient populations.

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“…Therefore, while antidiabetic medicines for stroke in patients with DM are vigrously being developed [ 118 ], further studies should also concentrate on potential mechanism of DM-induced different phase of stroke [ 119 ]. This might be helpful in identifying specific pathogenic mechanisms underlying cerebral damage caused by DM potentiated stroke.…”

Section: Potential Dm-induced Mechanisms Leading To Diabetic Strokmentioning

confidence: 99%

Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus

Xing¹,

Tang²,

Lei³

et al. 2020

Aging and disease

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The goal of this review was to summarize current biochemical mechanisms of and risk factors for diabetic brain injury. We mainly summarized mechanisms published in the past three years and focused on diabetes induced cognitive impairment, diabetes-linked Alzheimer's disease, and diabetic stroke. We think there is a need to conduct further studies with increased sample sizes and prolonged period of follow-ups to clarify the effect of DM on brain dysfunction. Additionally, we also think that enhancing experimental reproducibility using animal models in conjunction with application of advanced devices should be considered when new experiments are designed. It is expected that further investigation of the underlying mechanisms of diabetic cognitive impairment will provide novel insights into therapeutic approaches for ameliorating diabetes-associated injury in the brain.

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Diabetic aggravation of stroke and animal models

Cited by 23 publications

References 352 publications

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?Comorbidity and age in the modelling of stroke: are we still failing to consider the characteristics of stroke patients?

Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus

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