misoprostol and Infarction--Middle-Cerebral-Artery

Vaginal prostaglandin pessaries are considered safe and effective method of abortion within the first two trimesters of pregnancy. We present a case of a young woman, with no known risk factors for cerebrovascular events, who developed a cryptogenic stroke following administration of intravaginal Misoprostol. Case report and review of the relevant literature. A 30-year-old woman presented with right hemiparesis and aphasia after having received three 600 microg tablets of intravaginal Misoprostol for an elective abortion earlier in the day. A brain MRI revealed an acute ischemic infarction in the left middle cerebral artery territory. An extensive workup for possible etiologies was negative. Intravaginal Misoprostol may be associated with stroke in young women. Further study is required to determine if this case represents an isolated incident, or a true association.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Legal; Administration, Intravaginal; Adult; Dose-Response Relationship, Drug; Female; Humans; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Misoprostol; Pessaries; Pregnancy; Stroke

Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

Topics: Animals; Anti-Ulcer Agents; Brain; Brain Ischemia; Cerebral Arteries; Cerebral Infarction; Cerebrovascular Circulation; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Immunohistochemistry; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Knockout; Misoprostol; Neuroprotective Agents; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Prostaglandin E, EP4 Subtype; Reperfusion Injury; Time Factors