Small blood vessel models are being grown in a lab to help researchers investigate the possible causes of cerebral small vessel disease. They stated that they hope to find viable treatments for the ailment, which can affect patients with type 2 diabetes and high blood pressure. Although the results are encouraging, experts warn that there is still much work to be done in this area of study. In order to determine what causes small blood vessel-like models to leak in people with specific medical conditions that raise the risk of vascular dementia and stroke, scientists at Cambridge University in England have grown the models in a lab. The journal Stem Cell Reports published the study’s findings today.
Small vessel disease (SVD) of the brain primarily occurs in two forms. The most prevalent usually affects people in their middle years and is linked to type 2 diabetes and elevated blood pressure. People in their mid-30s are typically found with the other rare form, which is inherited. A COL4 gene mutation is one of the causes. Researchers at Cambridge’s Victor Philip Dahdaleh Heart and Lung Research Institute used skin samples from patients suffering from a rare form of SVD brought on by COL4 gene mutations. Induced pluripotent stem cells, which can differentiate into nearly any type of cell in the body, were produced using these. By using these cells to create new cells, the researchers were able to model the disease that affects the brain vessels. The complex support system that surrounds cells, known as the extracellular matrix, was disrupted by the mutations in this particular form of SVD, according to the scientists. Tight junctions were especially affected by this disruption, which made the blood vessels leaky. The overproduction of molecules known as matrix metalloproteinases (MMPs), which are required to preserve the extracellular matrix’s structure, was also linked to the disturbance that the researchers saw. The group used medications that block MMPs to treat the cells. To do this, they employed the anti-cancer medication marimastat, the antibiotic doxycycline, or both. According to the researchers, blocking the MMPs with medication halted the leak and undid the harm. They did point out that these medications can have harmful side effects.
SVD patients are routinely treated by Dr. Sean Savitz, a professor and the director of the Institute for Stroke and Cerebrovascular Diseases at UTHealth Houston. He expressed his admiration for the study’s conclusions to Medical News Today, but he issued a warning, noting that the researchers only examined rare genetic mutation cases. This is a very well-done study that raises some interesting questions about the biological and molecular alterations that may be underlying some of the pathologies observed in brains affected by small vessel disease (SVD). Not involved in the study, Savitz stated, SVD is very common, especially in older patients with vascular risk factors. He continued, It’s very interesting to use skin cells to recapitulate the conditions in small vessel disease. The fact that a common antibiotic could undo some of the changes seen was intriguing. But we must remember that the patients from whom the cells were taken had uncommon genetic mutations.
According to the researchers, approximately half (45%) of dementia cases globally and roughly one-fifth of ischemic strokes are caused by SVD. These happen when the brain’s blood and oxygen supply are cut off by a blood clot. They represent the most prevalent kind of stroke. According to an article published in Advances in Clinical and Experimental Medicine, cerebral small vessel disease is the most prevalent, progressive, and chronic type of vascular disease. It impacts the capillaries, arterioles, and tiny veins that supply the brain’s deep structures, including the white matter. According to Dr. Shae Datta, director of cognitive neurology at NYU Langone Hospital—Long Island and co-director of NYU Langone’s Concussion Center in New York, SVD causes cognitive impairment, ischemic or hemorrhagic stroke, problems with mobility, and neuropsychiatric symptoms. Datta, who was not involved in the study, told Medical News Today that regular exercise, healthy diet, Mediterranean diet, folic acid, and vitamin B12 and avoiding adverse lifestyle factors like smoking, excess alcohol, or high dietary sodium, are all associated with having fewer SVD features in observational studies.
According to Dr. Catherine Arnold, a neurologist at Northwell Lenox Hill in New York who was not involved in the study, there are typically multiple coexisting conditions with SVD. These may obstruct the course of therapy. In an interview with Medical News Today, Arnold stated, The results of this study allow a better understanding of some of the potential mechanisms behind the development of small vessel disease (SVD) and potential mechanisms for future treatments. However, this study alone does not provide enough clarity or insight to change practice entirely, given the likelihood of multiple co-existing processes that contribute to the disease, the speaker continued. Future research is necessary to determine whether the findings hold true for the majority of patients with cerebral small vessel disease who also have vascular risk factors like diabetes and hypertension, according to Savitz. Therefore, the results of these experiments cannot be immediately applied to a clinical setting; however, the study lays the groundwork for particular future treatment development directions. Other than vascular risk factor modifications, which include blood pressure, glucose, cholesterol, and adherence to a healthy diet, we do not currently have any specific treatments.
Treating the underlying cause of a condition, such as an ischemic stroke, is often the first step in treatment. According to Morales, secondary prevention strategies often involve the use of statins, glycemic control, antihypertensives, antithrombotics, and other medications in addition to encouraging social interaction, a Mediterranean diet, and frequent exercise. Medication side effects can contribute to compliance issues, which can arise frequently. Is it effective? Evidence suggests that some of the effects and progression of vascular disease can be mitigated by our current strategies; however, more effective precision-based medical strategies that target these mechanistic pathways are clearly needed.
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