Each year, approximately 795,000 people experience a new or recurrent
stroke. Of all
strokes, 84% are ischemic, 13% are
intracerebral hemorrhage (ICH)
strokes, and 3% are
subarachnoid hemorrhage strokes. Despite the decreased incidence of
ischemic stroke, there has been no change in the incidence of
hemorrhagic stroke in the last decade. ICH is a devastating disease 37-38% of patients between the ages of 45 and 64 die within 30 days. In an effort to prevent ischemic and
hemorrhagic strokes we and others have been studying the role of
prostaglandins and their receptors.
Prostaglandins are bioactive
lipids derived from the metabolism of
arachidonic acid. They sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. Most
prostaglandins are produced from specific
enzymes and act upon cells via distinct
G-protein coupled receptors. The presence of multiple
prostaglandin receptors cross-reactivity and coupling to different signal transduction pathways allow differentiated cells to respond to
prostaglandins in a unique manner. Due to the number of
prostaglandin receptors,
prostaglandin-dependent signaling can function either to promote neuronal survival or injury following acute excitotoxicity,
hypoxia, and stress induced by ICH. To better understand the mechanisms of neuronal survival and neurotoxicity mediated by
prostaglandin receptors, it is essential to understand downstream signaling. Several groups including ours have discovered unique roles for
prostaglandin receptors in rodent models of
ischemic stroke, excitotoxicity, and
Alzheimer disease, highlighting the emerging role of
prostaglandin receptor signaling in
hemorrhagic stroke with a focus on cyclic-
adenosine monophosphate and
calcium (Ca(2+)) signaling. We review current ICH data and discuss future directions notably on
prostaglandin receptors, which may lead to the development of unique therapeutic targets against
hemorrhagic stroke and
brain injuries alike.