Prostacyclin receptor deletion aggravates hippocampal neuronal loss after bilateral common carotid artery occlusion in mouse

Abstract

Transient global cerebral ischemia causes delayed neuronal death in the hippocampal CA1 region. It also induces an increase in cyclooxygenase 2 (COX-2), which generates several metabolites of arachidonic acid, known as prostanoids, including prostacyclin (PGI2). To determine the role of the PGI2 receptor (IP) in post-ischemic delayed cell death, wild-type and IP knockout (IP−/−) C57Bl/6 mice were subjected to 12-min bilateral common carotid artery occlusion or sham surgery, followed by 7 days of reperfusion. In the sham-operated mice, no statistical difference in CA1 hip-pocampal neuronal density was observed between the wild-type (2836±18/mm2) and IP−/− (2793±43/mm2) mice. Interestingly, in animals subjected to ischemia, surviving neuronal density in wild-type mice decreased to 50.5±7.9% and that of IP−/− mice decreased to 23.0±4.5% of their respective sham-operated controls (P<0.05). The results establish a role for the IP receptor in protecting pyramidal hippocampal neurons after this global ischemic model and suggest that IP receptor agonists could be developed to prevent delayed pyramidal neuronal cell death.

Importance of normothermia control in investigating delayed neuronal injury in a mouse global ischemia model

“…Neuronal injury was evaluated as previously described (Wei et al, 2008). In brief, 7 days after ischemia, animals were euthanized with sodium pentobarbital (35–50 mg/kg intraperitoneally) and transcardially perfused with 0.9% saline, followed by 4% paraformaldehyde.…”

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…Prostacyclin receptor deletion has been shown to aggravate hippocampal neuronal loss caused by ischemia (Wei et al, 2008) and cortical cell loss after traumatic brain injury (Lundblad et al, 2008). These experiments indirectly suggest that IP receptors could promote neuronal survival.…”

Sustained Neurological Recovery After Stroke in Aged Rats Treated With a Novel Prostacyclin Analog

“…PGI 2 induces vasodilation, is a potent inhibitor of platelet aggregation, and reduces microvascular permeability 1 . PGI 2 IP receptor deficient (IP −/− ) mice displayed exacerbated neuronal death following brain ischemia 2, 3 . In addition, PGI 2 analogs significantly reduced ischemic brain injury 2, 4–6 .…”