Involvement of ROS in BBB dysfunction.
The blood-brain barrier (BBB) forms a protective barrier around the brain, with the important function of maintaining brain homeostasis. Pathways thought to initiate BBB dysfunction include the kinin system, excitotoxicity, neutrophil recruitment, mitochondrial alterations and macrophage/microglial activation, all of which converge on the same point--reactive oxygen species (ROS). Interestingly, ROS also provide a common trigger for many downstream pathways that directly mediate BBB compromise such as oxidative damage, tight junction (TJ) modification and matrix metalloproteinases (MMP) activation. These observations suggest that ROS are key mediators of BBB breakdown and implicate antioxidants as potential neuroprotectants in conditions like stroke and traumatic brain injury (TBI). This review explores some of the pathways both upstream and downstream of ROS that have been implicated in increased BBB permeability and discusses the role of ROS and antioxidants in neuropathology.
Pun
Pamela B L
PB
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
Lu
Jia
J
Moochhala
Shabbir
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases