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(Stroke. 2009;40:3139.)
© 2009 American Heart Association, Inc.

Research Letters

Cyclo-Oxygenase-2 Mediates Hyperbaric Oxygen Preconditioning-Induced Neuroprotection in the Mouse Model of Surgical Brain Injury

Vikram Jadhav, MD, PhD; Robert P. Ostrowski, MD, PhD; Wenni Tong, BS; Brenden Matus; Rachel Jesunathadas, BS John H. Zhang, MD, PhD

From the Departments of Physiology and Pharmacology (V.J., R.P.O., W.T., B.M., R.J., J.H.Z.), Neurosurgery (J.H.Z.), and Anesthesiology (J.H.Z.), Loma Linda University, School of Medicine, Loma Linda, Calif.

Correspondence to John H. Zhang, MD, PhD, Department of Neurosurgery, Loma Linda University Medical Center, 11234 Anderson Street, Room 2562B, Loma Linda, CA 92350. E-mail johnzhang3910{at}yahoo.com

Background and Purpose— We investigated the role of cyclo-oxygenase-2 (COX-2) in mechanisms of hyperbaric oxygen preconditioning (HBO-PC) in the mouse model of surgical brain injury (SBI).

Methods— C57BL mice were administered 100% oxygen for 1 hour at 2.5 atmosphere absolute for 5 consecutive days and subjected to SBI. Neurological status and brain edema were evaluated at 24 hours and 72 hours after the brain insult. Fluorescent immunostaining and Western blotting were performed to study hypoxia-inducible factor-1 and COX-2, respectively. Two doses of COX-2 inhibitor, NS398 (3 mg/kg and 10 mg/kg) were used to verify the role of COX-2 signaling pathway in the mechanism of HBO-PC.

Results— HBO-PC improved neurological status and decreased brain edema at 24 hours and 72 hours after SBI. HBO-PC by itself and SBI independently increased COX-2 levels by 2-fold and 4-fold, respectively. HBO-PC, however, reduced increase in hypoxia-inducible factor-1 and COX-2 expression after SBI. The HBO-PC-induced improvement in neurological status and brain edema was reversed by a suboptimal dose of the COX-2 inhibitor, NS398 (10 mg/kg intraperitoneally; 1/4th of dose shown to provide neuroprotection), which itself had no effect on investigated end points.

Conclusions— HBO-PC attenuates postoperative brain edema and improves neurological outcomes after SBI. The HBO-PC-induced neuroprotection is mediated through COX-2 signaling pathways.

Key Words: brain edema • brain injury • cyclo-oxygenase-2 • hyperbaric oxygen • preconditioning • surgical neuroprotection