Rodent stroke models provide the experimental backbone for the in vivo determination of the mechanisms of cell death and neural repair, and for the initial testing of neuroprotective compounds. Less than 10 rodent models of focal stroke are routinely used in experimental study. These vary widely in their ability to model the human disease, and in their application to the study of cell death or neural repair. Many rodent focal stroke models produce large infarcts that more closely resemble malignant and fatal human infarction than the average sized human stroke. This review focuses on the mechanisms of ischemic damage in rat and mouse stroke models, the relative size of stroke generated in each model, and the purpose with which focal stroke models are applied to the study of ischemic cell death and to neural repair after stroke.

https://link.springer.com/content/pdf/10.1602%2Fneurorx.2.3.396.pdf

Rodent models of focal stroke: size, mechanism, and purpose.

Astragalus membranaceus Bunge has been used to treat numerous diseases for thousands of years. As the main active substance of Astragalus membranaceus Bunge, astragaloside IV (AS-IV) also demonstrates the potent protective effect on focal cerebral ischemia/reperfusion, cardiovascular disease, pulmonary disease, liver fibrosis, and diabetic nephropathy. Based on studies published during the past several decades, the current state of AS-IV research and the pharmacological effects are detailed, elucidated, and summarized. This review systematically summarizes the pharmacological effects, metabolism mechanism, and the toxicity of AS-IV. AS-IV has multiple pharmacologic effects, including anti-inflammatory, antifibrotic, antioxidative stress, anti-asthma, antidiabetes, immunoregulation, and cardioprotective effect via numerous signaling pathways. According to the existing studies and clinical practices, AS-IV possesses potential for broad application in many diseases.

Research review on the pharmacological effects of astragaloside IV.

Pharmacological effects of Astragaloside IV: a literature review

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

https://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2015.116

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review.

Owing to a dramatic increase in average life expectancy and the Family Planning program of the 1970s - 1990s, China is rapidly becoming an aging society. Therefore, the investigation of healthspan-extending drugs becomes more urgent. Astragalus membranaceus (Huangqi) is a major medicinal herb that has been commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders, or marketed as life-prolonging extracts for human use in China, for more than 2000 years. The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins. Pharmacological research indicates that the extract component of Astragalus membranaceus can increase telomerase activity, and has antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system. Our review focuses on the function and the underlying mechanisms of Astragalus membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer effects, based on experimental and clinical studies.

Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic.

Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia.

Background and Purpose. The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease.



Methods. A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale.



Results. CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%± 10% in grade 0-I, 60%± 10% in grade II, and 40%± 10% in grade III, P < .001); for PVH (80%± 10% in grade 0-I, 60%± 10% in grade II, and 40%± 10% in grade III, P < .001).



Conclusions. Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.

Ding Ding

Papers

Astragaloside IV protects against ischemic brain injury in a murine model of transient focal ischemia.

Relationship between cerebral vasomotor reactivity and white matter lesions in elderly subjects without large artery occlusive disease.

Plasma level of sICAM-1 is associated with the extent of white matter lesion among asymptomatic elderly subjects.