title: Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the brain after experimental subarachnoid hemorrhage in rats.
abstract: We have previously shown that astaxanthin (ATX) reduces the blood-brain barrier (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage (SAH) insults. However, the underlying mechanisms remain unclear. It is known that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9 (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we investigated whether ATX could ameliorate MMP-9 activation and expression in a rat model of SAH. A total of 144 rats were randomly divided into the following groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous blood into the prechiasmatic cistern. ATX (20 μl of 0.1 mmol) or vehicle was administered intracerebroventricularly 30 min after SAH induction. Mortality, neurological function, brain edema and blood-brain barrier (BBB) permeability were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were used to analyze MMP-9 expression and activity in brain samples. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were also evaluated at 24h. Our data indicated that ATX could significantly reduce the expression and activity of MMP-9, leading to the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL-positive cells at 24h but not 72 h after SAH. The ATX-mediated down-regulation of MMP-9 was correlated with the decreased levels of IL-1β, TNF-α, oxidative stress, activated microglia and infiltrating neutrophils. These results suggest that the neurovascular protection of ATX in SAH is partly associated with the inhibition of MMP-9 expression and activity.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: zhangxsp@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Tian-Wei
authors.initials: TW
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: hang_neurosurgery@163.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Hang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001813:Blood-Retinal Barrier / Q000254:growth & development / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors; D024341:Xanthophylls / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D024341:Xanthophylls; D008315:Malondialdehyde; C005948:astaxanthine; D020780:Matrix Metalloproteinase 9
keywords: Astaxanthin; Early brain injury; Matrix metalloproteinase-9; Subarachnoid hemorrhage