Stroke: overview and tools for your research

Explore the complex pathology of stroke and access the tools you need to advance your research in stroke and its associated diseases.

Overview

• Stroke and stroke-associated diseases
• Autophagy in ischemic stroke – interactive pathway
• Small vessel disease, CADASIL, and vascular dementia – Professor Markus video
• Key targets in stroke
• Diagnostic stroke biomarkers
• Prognostic stroke biomarkers
• References

Stroke and stroke-associated diseases

Stroke is an aspect of cardiovascular disease, resulting from an interruption of the blood supply to a part of the brain. Such an interruption is caused by a clot blocking a blood vessel (ischemic stroke) or as the result of a blood vessel burst (hemorrhagic stroke). Ischemic stroke accounts for around 80% of all strokes.

Stroke is a major risk factor for the development of vascular cognitive impairment (VCI), vascular dementia (VaD), and Alzheimer’s disease (AD)^1,2. Current evidence suggests that 25-30% of ischemic stroke survivors develop immediate or delayed VCI or VaD³. 

The cerebral small-vessel disease is strongly associated with ischemic stroke and dementia. The most prevalent inherited cause of the cerebral small-vessel disease is CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a disorder linked to mutations in NOTCH3. The most common symptoms of CADASIL are small ischemic strokes and/or transient ischemic attacks and cognitive impairment, appearing in middle age, that may progress to VaD⁴.

Autophagy in ischemic stroke – interactive pathway

Recent studies have found autophagy to be a key regulatory factor in ischemic stroke, unveiling a new range of potential therapeutic targets for neuroprotection⁵.

Explore the role of autophagy signaling pathways in ischemic stroke with our interactive pathway.

Click on the preview below to download the interactive pathway.

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​​Small vessel disease, CADASIL, and vascular dementia

Learn more about the link between stroke, small vessel disease, and vascular dementia from Professor Hugh Markus, Professor of Stroke Medicine at the University of Cambridge.

Here Prof Markus discusses the connection between vascular risk factors and AD and highlights the value of studying CADASIL as a model for pure vascular dementia. He also talks us through recently discovered monogenic forms of small vessel disease such as HTRA1, COL4A1, COL4A2.

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Key targets in stroke

Key targets in stroke include HTRA1, NOTCH3, COL4A1/2, VEGFA, ACHE, BCHE. Mutations in NOTCH3 and HTRA1 genes are responsible for the development of CADASIL, which causes stroke⁶. COL4A1 mutations have been identified in adult patients with small-vessel disease and can result in stroke⁷.

VEGF-A is expressed at low levels in the adult human brain, but it is upregulated in response to stroke, predominantly in the stroke/penumbra area. VEGF-A was shown to promote angiogenesis, neurogenesis, and neuroprotection, leading to improved functional recovery. VEGF-A is, therefore, a potential candidate for treatment in ischemic stroke⁸.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the acetylcholine-hydrolyzing enzymes, may be potentially used as diagnostic biomarkers in stroke⁹. Additionally, BChE may serve as a biomarker for post-stroke dementia¹⁰.

Diagnostic stroke biomarkers

Diagnostic stroke biomarkers can be used to differentiate between ischemic and hemorrhagic strokes, which require distinct treatment approaches. Diagnostic stroke biomarkers can also distinguish between ischemic strokes and stroke mimics such as migraine, seizure, or hypoglycemia. Finally, biomarkers can identify the etiological subtype of ischemic strokes, which is essential because prognosis, risk of recurrence, and management options differ greatly between subtypes.

Advance your research in stroke with our SimpleStep ELISA^® kits for diagnostic stroke biomarkers. Our SimpleStep ELISA^® kits provide you with sensitive and reliable results within 90-minutes and are suitable for a wide range of samples.

Prognostic stroke biomarkers 

Prognostic stroke biomarkers can accurately predict mortality risk, functional outcomes, and specific complications after stroke such as post-stroke cognitive impairment.

Explore prognostic biomarkers in stroke with our SimpleStep ELISA^® kits.

References

1. Vijayan, M., Reddy, P.H. Stroke, vascular dementia, and Alzheimer's disease: molecular links. J Alzheimers Dis. 54, 427–443 (2016).
2. Wiesmann, M., Kiliaan, A.J., Claassen, J.A. Vascular aspects of cognitive impairment and dementia. J Cereb Blood Flow Metab. 33, 1696–1706 (2013).
3. Kalaria, R.N., Akinyemi, R., Ihara, M. Stroke injury, cognitive impairment and vascular dementia. Biochim Biophys Acta.1862, 915–925 (2016).
4. Wang, M.M. CADASIL. Handb Clin Neurol. 148, 733–743 (2018).
5. Papadakis, M., et al. Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy. Nat Med 19, 351–357 (2013).
6. Boehme, A.K., Esenwa, C., Elkind, M.S. Stroke risk factors, genetics, and prevention. Circ Res.120, 472–495 (2017).
7. Lanfranconi, S., Markus, H.S. COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke 41, e513–e518 (2010).
8. Geiseler SJ, Morland C. The janus face of VEGF in stroke. Int J Mol Sci. 19, 1362 (2018).
9. Ben Assayag, E., et al. Serum cholinesterase activities distinguish between stroke patients and controls and predict 12-month mortality. Mol Med. 16, 278–286 (2010).
10. Chen, Y.C., et al. Serum level and activity of butylcholinesterase: a biomarker for post-stroke dementia. J Clin Med. 8, 1778. (2019).