Lipocalin-prostaglandin D synthase is a critical beneficial factor in transient and permanent focal cerebral ischemia

S. Saleem, Z. A. Shah, Y. Urade, S. Doré

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Prostaglandin D2 (PGD2) is the most abundant prostaglandin produced in the brain. It is a metabolite of arachidonic acid and synthesized by prostaglandin D2 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.

Original languageEnglish (US)
Pages (from-to)248-254
Number of pages7
JournalNeuroscience
Volume160
Issue number1
DOIs
StatePublished - Apr 21 2009
Externally publishedYes

Keywords

  • cerebral ischemia
  • middle cerebral artery occlusion
  • mouse
  • PGD
  • prostaglandins

ASJC Scopus subject areas

  • Neuroscience(all)

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