Brain Revascularization Therapy Strategy

Brain Revascularization

Angiogenesis is activated under situations of brain hypoxia, where insufficient endogenous signals reach sufficient functional vessels to locate brain vasculature. Therefore, pro-angiogenic therapy is a logistical solution to this challenge. demonstrated that an increase in brain angiogenesis indicates an increase in endothelial cells that can result in the performance of the neurovascular unit and cerebral blood flow.

Therefore, extracellular regulatory signals secreted by the microvasculature are generated, facilitating the proliferation and migration of neural stem cells as well as the supply of nutrients and oxygen, promoting neurological recovery and improving cognitive function (Hatakeyama et al., 2020).

Among the pro-angiogenic factors used to achieve brain revascularization, VEGF-A is the most potent candidate and is widely used because of its angiogenic and neuroprotective effects (Korpisalo and Yla-Herttuala, 2010; Lange et al., 2016; Shim and Madsen, 2018). ). The relevant feature of the function of VEGF is related to its interaction, interaction with the ECM, which orders its localization in tissues and controls the outcome of the angiogenic process (Martino et al., 2015).

Therefore, identifying specific signals involved in microvascular disruption in the CNS is a candidate for angiogenic therapy for the detection of neurovascular tissue in stroke, neurodegeneration, and aging.

Therapeutic Factor

  • Growth factor. The most potent and widely used pro-angiogenic factor to achieve brain revascularization is VEGF-A, due to its angiogenic and neuroprotective effects (Lange et al., 2016; Shim and Madsen, 2018). It has been shown that systemic or intracerebral soluble VEGF after stroke increases BBB opening, increases edema, and increases disorganized and immature blood vessels, while its antagonist reduces injury (Ma et al., 2012).
  • Bioactive Substances. Apart from vascular-derived growth factors, bioactive substances, such as ibutilide and astragaloside IV, promote angiogenesis and recovery from ischemic stroke.
  • Considerations. Dosage and Spatio-temporal control of delivery factors to prevent aberrant blood vessel formation, BBB leakage, gliomas, and other potential unwanted side effects (Manoonkitiwongsa et al., 2004; Ozawa et al., 2004; Uccelli et al., 2019; von Degenfeld et al., 2006), should be taken into account to achieve a better clinical outcome.

Nanotechnology Platforms

Nanotherapy is gaining disease momentum as a viable medical option for CNS treatment. Nanotechnology platforms, modern therapies, and biomaterials are tools that drive the efficient and safe delivery of therapeutic factors.

  • Nanocarrier. Currently, nano carrier-based clinical trials are underway for CNS revascularization in ALS patients by administering an intracerebroventricular solution containing an implantable drug delivery system consisting of an implantable catheter and SynchroMed II.
  • Gene Therapy System. Therapies based on gene therapy approaches, divided into viral and non-viral vectors, have emerged in recent years as a potential tool for the treatment of many congenital, acquired, and age-related diseases (Ingusci et al., 2019). Gene therapy includes opportunities to develop gene info, translation of endogenous protein/factor genes, providing the possibility to achieve stable or inducible therapeutic gene expression, as well as specific expression in target cells...
  • Another Approach with Combined Systems. To deliver continuous and localized amounts of angiogenic factors to brain tissue, cell encapsulation provides an attractive approach. In this way, a polymer matrix surrounded by a semi-permeable membrane enveloping the cell is engineered to defend it against immune cell-mediated protection and antibody-mediated rejection. Moreover, this membrane regulates bidirectional diffusion, enabling controlled and sustained delivery of therapeutic factors (Gurruchaga et al., 2015; Orive et al., 2003).


Gallego, I., Villate-Beitia, I., Saenz-del-Burgo, L., Puras, G., & Pedraz, J. L. (2022). Therapeutic Opportunities and Delivery Strategies for Brain Revascularization in Stroke, Neurodegeneration, and Aging. Pharmacology Review, 74(2), 439-461.

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