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blood_brain_barrier_disruption [2021/08/03 20:05]
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-The [[blood-brain barrier]] (BBB) can be easily destroyed by [[stroke]], which is one of the main factors responsible for [[macrophage infiltration]] and central nervous [[inflammation]].  
-The blood-brain barrier represents a fundamental limitation in treating neurological disease because it prevents all neuropeptides from reaching the central nervous system (CNS). Currently, there is no efficient method to permanently bypass the blood-brain barrier. 
-Zang et al. reported the protective effects of Trelagliptin against BBB injury and [[macrophage infiltration]]. The results indicate that the infraction volume, the neurological score, and macrophage infiltration staining with [[CD68]] were increased in [[middle cerebral artery occlusion]] (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction [[zonula occludens protein-1]] (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of [[ZO-1]], and elevated expression level of [[CXCL1]] by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. The results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood-brain barrier in the brains of MCAO mice 
-((Zang L, Yang B, Zhang M, Cui J, Ma X, Wei L. [[Trelagliptin]] Mitigates [[Macrophage Infiltration]] by Preventing the Breakdown of the [[Blood-Brain Barrier]] in the Brain of [[Middle Cerebral Artery Occlusion]] Mice. Chem Res Toxicol. 2021 Mar 17. doi: 10.1021/acs.chemrestox.0c00323. Epub ahead of print. PMID: 33728903.)). 
-Although ongoing research has yielded some potential options for future [[glioblastoma]] therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications 
-((Hendricks BK, Cohen-Gadol AA, Miller JC. Novel delivery methods bypassing the  
-blood-brain and blood-tumor barriers. Neurosurg Focus. 2015 Mar;38(3):E10. doi: 
-10.3171/2015.1.FOCUS14767. PubMed PMID: 25727219.)). 
-Current strategies for enhancing the delivery of therapies across the BBB to the tumor is discussed, with a distinction made between strategies that seek to disrupt the BBB and those that aim to circumvent it in the article of Azad et al. 
-((Azad TD, Pan J, Connolly ID, Remington A, Wilson CM, Grant GA. Therapeutic 
-strategies to improve drug delivery across the blood-brain barrier. Neurosurg 
-Focus. 2015 Mar;38(3):E9. doi: 10.3171/2014.12.FOCUS14758. PubMed PMID: 25727231.)). 
-Histological investigations have shown that disruption of the [[blood brain barrier]] (BBB) is well correlated with the degradation of collagen IV, a major component of the BBB 
-((Egashira Y, Zhao H, Hua Y, Keep RF, Xi G. White matter injury after subarachnoid hemorrhage: role of blood-brain barrier disruption and matrix metalloproteinase-9. Stroke. 2015;46(10):2909–2915.)). 
-Among other basal lamina proteins, collagen IV is often degraded by metalloproteinase-9 (MMP-9) 
-[[Triolein]] emulsion infusion into the [[carotid artery]] has been reported to induce temporary and reversible opening of the [[blood brain barrier]] by increasing vascular permeability. 
-Transmucosal delivery of [[glial derived neurotrophic factor]] (GDNF) is equivalent to direct intrastriatal injection at ameliorating the behavioral and immunohistological features of [[Parkinson disease]] in a murine model. Mucosal grafting of arachnoid defects is a technique commonly used for endoscopic skull base reconstruction and may represent a novel method to permanently bypass the blood-brain barrier 
-((Bleier BS, Kohman RE, Guerra K, Nocera AL, Ramanlal S, Kocharyan AH, Curry WT, 
-Han X. Heterotopic Mucosal Grafting Enables the Delivery of Therapeutic 
-Neuropeptides Across the Blood Brain Barrier. Neurosurgery. 2016 
-Mar;78(3):448-57. doi: 10.1227/NEU.0000000000001016. PubMed PMID: 26352099.