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.