scholarly journals Pharmacological targeting of the PDGF-CC signaling pathway for blood–brain barrier restoration in neurological disorders

2016 ◽  
Vol 167 ◽  
pp. 108-119 ◽  
Author(s):  
Sebastian A. Lewandowski ◽  
Linda Fredriksson ◽  
Daniel A. Lawrence ◽  
Ulf Eriksson
2020 ◽  
Vol 18 (9) ◽  
pp. 713-722 ◽  
Author(s):  
Ganji Hong ◽  
Ying Yan ◽  
Yali Zhong ◽  
Jianer Chen ◽  
Fei Tong ◽  
...  

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.


2021 ◽  
Author(s):  
Chiara Borsari ◽  
Erhan Keles ◽  
Andrea Treyer ◽  
Martina De Pascale ◽  
Paul Hebeisen ◽  
...  

Here we present the first pyrimido-pyrrolo-oxazine-based mTOR kinase inhibitor (11) predicted to penetrate the blood brain barrier (BBB). Thus, 11 has a potential in treatments of neurological disorders.


2020 ◽  
Vol 8 (21) ◽  
pp. 1458-1458
Author(s):  
Sheng-Long Chen ◽  
Geng-Xin Cai ◽  
Hong-Guang Ding ◽  
Xin-Qiang Liu ◽  
Zhong-Hua Wang ◽  
...  

2019 ◽  
Vol 20 (23) ◽  
pp. 6010 ◽  
Author(s):  
Jacopo Junio Valerio Branca ◽  
Mario Maresca ◽  
Gabriele Morucci ◽  
Tommaso Mello ◽  
Matteo Becatti ◽  
...  

Cadmium (Cd) is a highly toxic environmental pollutant released from the smelting and refining of metals and cigarette smoking. Oral exposure to cadmium may result in adverse effects on a number of tissues, including the central nervous system (CNS). In fact, its toxicity has been related to neurological disorders, as well as neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Under normal conditions, Cd barely reaches the brain in adults because of the presence of the blood–brain barrier (BBB); however, it has been demonstrated that Cd-dependent BBB alteration contributes to pathogenesis of neurodegeneration. However, the mechanism underlying Cd-dependent BBB alteration remain obscure. Here, we investigated the signaling pathway of Cd-induced tight junction (TJ), F-actin, and vimentin protein disassembly in a rat brain endothelial cell line (RBE4). RBE4 cells treated with 10 μM cadmium chloride (CdCl2) showed a dose- and time-dependent significant increase in reactive oxygen species (ROS) production. This phenomenon was coincident with the alteration of the TJ zonula occludens-1 (ZO-1), F-actin, and vimentin proteins. The Cd-dependent ROS increase elicited the upregulation of GRP78 expression levels, a chaperone involved in endoplasmic reticulum (ER) stress that induces caspase-3 activation. Further signal profiling by the pannexin-1 (PANX1) specific inhibitor 10Panx revealed a PANX1-independent increase in ATP spillage in Cd-treated endothelial cells. Our results point out that a ROS-dependent ER stress-mediated signaling pathway involving caspase-3 activation and ATP release is behind the BBB morphological alterations induced by Cd.


2019 ◽  
Vol 20 (7) ◽  
pp. 1632 ◽  
Author(s):  
Michelle Erickson ◽  
William Banks

Age is associated with altered immune functions that may affect the brain. Brain barriers, including the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB), are important interfaces for neuroimmune communication, and are affected by aging. In this review, we explore novel mechanisms by which the aging immune system alters central nervous system functions and neuroimmune responses, with a focus on brain barriers. Specific emphasis will be on recent works that have identified novel mechanisms by which BBB/BCSFB functions change with age, interactions of the BBB with age-associated immune factors, and contributions of the BBB to age-associated neurological disorders. Understanding how age alters BBB functions and responses to pathological insults could provide important insight on the role of the BBB in the progression of cognitive decline and neurodegenerative disease.


Aging Cell ◽  
2016 ◽  
Vol 16 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Jong-Chan Park ◽  
Sung Hoon Baik ◽  
Sun-Ho Han ◽  
Hyun Jin Cho ◽  
Hyunjung Choi ◽  
...  

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