Illustration of brain blood vessels symbolizing VEGF balance in stroke treatment.

Unlocking the Mystery: How Brain Blood Vessel Differences Impact Stroke Treatment

Nico Varela in Health & Wellness November 2025 • 5 min read.

"New research reveals the crucial role of specific protein variations in intracranial atherosclerosis and moyamoya disease, paving the way for more targeted therapies."

The human brain relies on a complex network of blood vessels to function correctly. When these vessels become narrowed or blocked, it can lead to severe conditions like stroke. Intracranial atherosclerosis (ICAD) and moyamoya disease (MMD) are two such conditions, both characterized by narrowed arteries in the brain, but they differ significantly in how the body attempts to compensate by forming new blood vessels (collaterals). Understanding these differences at a molecular level is crucial for developing better treatments.

Vascular endothelial growth factor (VEGF) is a protein that plays a vital role in stimulating the growth of new blood vessels. However, not all VEGF is created equal. VEGF-A165, a specific form of VEGF, exists in two versions: one that promotes blood vessel growth (VEGF-A165a) and one that inhibits it (VEGF-A165b). The balance between these two versions can significantly impact how well the brain can compensate for blocked arteries.

Recent research has delved into the differing roles of VEGF-A165a and VEGF-A165b in ICAD and MMD, revealing key distinctions that could revolutionize treatment strategies. This article breaks down the study's findings, explaining how these protein variations influence the conditions and what this means for future therapies.

VEGF-A165a/b Ratio: A Key Differentiator in Brain Blood Vessel Diseases

Illustration of brain blood vessels symbolizing VEGF balance in stroke treatment.

A new study compared the levels of VEGF-A165a and VEGF-A165b in patients with ICAD and MMD. The results showed a significantly higher baseline ratio of VEGF-A165a to VEGF-A165b in MMD patients compared to those with ICAD. This suggests that MMD is characterized by a greater natural tendency to promote blood vessel growth, which aligns with its known propensity for collateral formation.

The study also investigated how treatments affect the VEGF-A165a/b ratio. Key findings include:

Surgical Intervention: In ICAD patients, surgical revascularization led to a rapid increase in the VEGF-A165a/b ratio within one week. This indicates that surgery can effectively stimulate blood vessel growth in ICAD.
Medical Management: Intensive medical management in ICAD patients also increased the VEGF-A165a/b ratio, but at a slower pace, peaking after three months. This suggests that lifestyle modifications and medication can gradually shift the balance towards promoting blood vessel growth.
MMD Response: Surgical intervention did not significantly alter the VEGF-A165a/b ratio in MMD patients, possibly because their baseline ratio is already high.

These results highlight the distinct molecular profiles of ICAD and MMD and how they respond differently to treatment. The VEGF-A165a/b ratio appears to be a crucial factor in determining the extent of collateral formation and the effectiveness of different therapies.

Personalized Stroke Treatment: A Future Shaped by Protein Understanding

The research sheds light on the complex interplay of proteins and blood vessel health in the brain. By understanding the specific roles of VEGF-A165a and VEGF-A165b in ICAD and MMD, doctors can move closer to personalized stroke treatments that target the underlying molecular mechanisms of each condition.

Future studies should focus on confirming these findings in larger patient groups and exploring how other factors, such as genetics and lifestyle, influence the VEGF-A165a/b ratio. Further research into how Insulin Growth Factor (IGF) affects levels of VEGF could lead to better long-term medical treatment.

Ultimately, this research paves the way for more effective therapies that promote blood vessel growth in ICAD and MMD, improving outcomes for individuals at risk of stroke and other cerebrovascular diseases. By targeting the VEGF-A165a/b ratio, scientists and clinicians can unlock new possibilities for preventing and treating these debilitating conditions.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.jstrokecerebrovasdis.2018.10.004, Alternate LINK

Title: Differential Expression Of Vascular Endothelial Growth Factor-A165 Isoforms Between Intracranial Atherosclerosis And Moyamoya Disease

Subject: Cardiology and Cardiovascular Medicine

Journal: Journal of Stroke and Cerebrovascular Diseases

Publisher: Elsevier BV

Authors: Hao Jiang, Juan F. Toscano, Michael Schiraldi, Shlee S. Song, Konrad H. Schlick, Oana M. Dumitrascu, Raymond Liou, Patrick D. Lyden, Jianwei Pan, Renya Zhan, Jeffrey L. Saver, Nestor R. Gonzalez

Published: 2019-02-01

Everything You Need To Know

What are the key differences between Intracranial atherosclerosis (ICAD) and moyamoya disease (MMD)?

Intracranial atherosclerosis (ICAD) and moyamoya disease (MMD) are both conditions characterized by narrowed arteries in the brain. The difference lies in how the brain attempts to compensate. ICAD involves narrowing of the arteries, while MMD often involves the formation of new blood vessels, or collaterals, to bypass the blockages. Understanding these differences is crucial for tailoring treatments because the underlying mechanisms and responses to therapies can vary significantly.

What is the role of VEGF-A165 in brain health?

VEGF-A165 is a specific form of Vascular Endothelial Growth Factor (VEGF), a protein that stimulates the growth of new blood vessels. The critical aspect is that VEGF-A165 has two versions, VEGF-A165a and VEGF-A165b. VEGF-A165a promotes blood vessel growth, and VEGF-A165b inhibits it. The ratio of these two versions is critical because it determines how well the brain can compensate for narrowed or blocked arteries in conditions like ICAD and MMD, impacting the formation of collateral vessels.

Why is the VEGF-A165a/b ratio important in the context of these brain conditions?

The ratio of VEGF-A165a to VEGF-A165b is important because it indicates the brain's capacity to form new blood vessels. A higher ratio of VEGF-A165a, which promotes blood vessel growth, suggests a greater ability to compensate for blockages. The study found that MMD patients have a naturally higher baseline ratio than ICAD patients, which aligns with MMD's tendency to form more collaterals. This ratio is a key differentiator in how these conditions respond to treatments. Monitoring and manipulating this ratio through therapies could potentially enhance treatment effectiveness.

How do treatments affect the VEGF-A165a/b ratio in ICAD and MMD?

In ICAD patients, surgical revascularization leads to a rapid increase in the VEGF-A165a/b ratio, indicating that surgery can effectively stimulate blood vessel growth. Intensive medical management also increases the ratio but at a slower pace. In contrast, surgical intervention does not significantly alter the VEGF-A165a/b ratio in MMD patients. These differing responses highlight how the balance of VEGF-A165a and VEGF-A165b can be manipulated to promote blood vessel growth in specific conditions.

How can this research lead to improved stroke treatments?

This research opens the door for personalized stroke treatment. By understanding the roles of VEGF-A165a and VEGF-A165b in ICAD and MMD, doctors can develop treatments that target the specific molecular mechanisms of each condition. This could involve therapies to boost VEGF-A165a levels or reduce VEGF-A165b, thereby promoting blood vessel growth and improving outcomes. The goal is to move away from a one-size-fits-all approach and tailor treatments to the individual needs of each patient, improving the effectiveness of stroke interventions.