title: Lipocalin-prostaglandin D synthase is a critical beneficial factor in transient and permanent focal cerebral ischemia.
abstract: Prostaglandin D(2) (PGD(2)) is the most abundant prostaglandin produced in the brain. It is a metabolite of arachidonic acid and synthesized by prostaglandin D(2) synthases (PGDS) via the cyclooxygenase pathway. Two distinct types of PGDS have been identified: hematopoietic prostaglandin D synthase (H-PGDS) and lipocalin-type prostaglandin D synthase (L-PGDS). Because relatively little is known about the role of L-PGDS in the CNS, here we examined the outcomes in L-PGDS knockout and wild-type (WT) mice after two different cerebral ischemia models, transient middle cerebral artery (MCA) occlusion (tMCAO) and permanent distal middle cerebral artery occlusion (pMCAO). In the tMCAO model, the MCA was occluded with a monofilament for 90 min and then reperfused for 4 days. In the pMCAO model, the distal part of the MCA was permanently occluded and the mice were sacrificed after 7 days. Percent corrected infarct volume and neurological score were determined after 4 and 7 days, respectively. L-PGDS knockout mice had significantly greater infarct volume and brain edema than did WT mice after tMCAO (P<0.01). Similarly, L-PGDS knockout mice showed greater infarct volume and neurological deficits as compared to their WT counterparts after pMCAO (P<0.01). Using the two models enabled us to study the role of L-PGDS in both early (tMCAO) and delayed (pMCAO) ischemic processes. Our findings suggest that L-PGDS is beneficial for protecting the brain against transient and permanent cerebral ischemia. These results provide a better understanding of the role played by the enzymes that control eicosanoid synthesis and how they can be utilized as potential targets to prevent damage following either acute or potentially chronic neurological disorders.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 365, Baltimore, MD 21205, USA.
authors.forename: S
authors.initials: S
authors.lastname: Saleem
authors.forename: Z A
authors.initials: ZA
authors.lastname: Shah
authors.forename: Y
authors.initials: Y
authors.lastname: Urade
authors.forename: S
authors.initials: S
authors.lastname: Doré
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D001929:Brain Edema / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000473:pathology / Q000523:psychology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012720:Severity of Illness Index; D014867:Water / Q000737:chemistry
chemical_list: D054834:Lipocalins; D014867:Water; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase