Citations 2
Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors
Griffith, Jessica I. , Rathi, Sneha , Zhang, Wenqiu , Zhang, Wenjuan , Drewes, Lester R. , Elmquist, William F. , Zhang, Wenqiu , Zhang, Wenjuan , Zhang, Wenqiu , Sarkaria, Jann N.
Pharmaceutics | December 14, 2020 | Volume: 12 | Issue: 12 | Pages: 1205
Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood–brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood–tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a “whole brain” approach to the treatment of brain tumors might be beneficial. We discuss various methods by which these obstacles might be overcome and assess how these strategies are progressing in the clinic. We believe that by approaching brain tumor treatment from this perspective, a new paradigm for drug delivery to brain tumors might be established.
Vascular dysfunction—The disregarded partner of Alzheimer's disease
Sweeney, Melanie D. , Montagne, Axel , Nation, Daniel A. , Schneider, Lon S. , Chui, Helena C., Harrington, Michael G. , Pa, Judy , Law, Meng , Wang, Danny J.J. , Jacobs, Russell E. , Doubal, Fergus , Ramirez, Joel , Dichgans, Martin , Love, Seth , Bath, Philip M. , Markus, Hugh S. , Salman, Rustam Al‐Shahi , Kalaria, Rajesh N., Werring, David J. , Moskowitz, Michael A., Katušić, Zvonimir S. , Lazarov, Orly , Rehman, Jalees , Wellington, Cheryl L. , González, Héctor M. , Yuan, Chun , Lockhart, Samuel N. , Hughes, Timothy M. , Chen, Christopher , Sachdev, Perminder S. , O’Brien, John T. , Pantoni, Leonardo , Gustafson, Deborah , Biessels, Geert Jan , Wallin, Anders , Wong, Adrian , Passmore, Peter , Barkof, Frederick, Muller, Majon , Román, Gustavo C. , Hamel, Édith , Seshadri, Sudha , Buchem, Mark A. van , Arvanitakis, Zoe , Drewes, Lester R. , Hachinski, Vladimir , Wardlaw, Joanna M. , Kalaria, Raj N. , Dichgans, Martin , O'Brien, John Tiernan , Wardlaw, Joanna Marguerite , Seshadri, Sudha , Sachdev, Perminder S , Sagare, Abhay P. , Chui, Helena C. , Black, Sandra E. , Nedergaard, Maiken , Benveniste, Helene , Iadecola, Costantino , Allan, Stuart McRae , Quinn, Terence J , Carare, Roxana Octavia , Touyz, Rhian M. , Williams, Steven , Lutz, Sarah E. , Minshall, Richard D. , Davis, Thomas P. , Gonzalez, Hector M , Skoog, Ingmar , Biessels, Geert Jan , Smith, Eric Edward , Mok, Vincent , Breteler, Monique M.B. , Gottesman, Rebecca F. , Schneider, Julie A. , Finch, Caleb E. , Toga, Arthur W. , Zloković, Berislav V. , Al-Shahi Salman, Rustam , Werring, David John , Wang, Danny J J
Alzheimer's & Dementia | January 11, 2019 | Volume: 15 | Issue: 1 | Pages: 158-167
Abstract Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.