Nasal Administration of Recombinant Osteopontin Attenuates Early Brain Injury After Subarachnoid Hemorrhage

Is this research settled enough that it should be rolled out to all hospitals?  What clinical trials are needed?  The Joint Commission should be responsible for something like this but they won't do anything. Its up to you to get it into the hospital you plan on visiting after your next stroke. If only we had a great stroke association that would take care of all these  survivor needs and make sure doctors and hospitals were up-to-date.
http://stroke.ahajournals.org/content/44/11/3189.abstract.html?etoc

1. Basak Caner Topkoru, MD;
2. Orhan Altay, MD;
3. Kamil Duris, MD;
4. Paul R. Krafft, MD;
5. Junhao Yan, MD, PhD;
6. John H. Zhang, MD, PhD

+ Author Affiliations

1. From the Departments of Physiology and Pharmacology (B.C.T., O.A., K.D., P.R.K., J.Y., J.H.Z.) and Neurosurgery (J.H.Z.), Loma Linda University School of Medicine, CA.

1. Correspondence to John H. Zhang, MD, PhD, Department of Neurosurgery, Loma Linda University, Loma Linda, CA 92534. E-mail johnzhang3910@yahoo.com

Abstract

Background and Purpose—Neuronal apoptosis is a key pathological process in subarachnoid hemorrhage (SAH)–induced early brain injury. Given that recombinant osteopontin (rOPN), a promising neuroprotectant, cannot pass through the blood–brain barrier, we aimed to examine whether nasal administration of rOPN prevents neuronal apoptosis after experimental SAH.

Methods—Male Sprague–Dawley rats (n=144) were subjected to the endovascular perforation SAH model. rOPN was administered via the nasal route and neurological scores as well as brain water content were evaluated at 24 and 72 hours after SAH induction. The expressions of cleaved caspase-3, phosphorylated focal adhesion kinase (FAK), and phosphorylated Akt were examined using Western blot analysis. Neuronal cell death was demonstrated with terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling. We also administered FAK inhibitor 14 and phosphatidylinositol 3-kinase inhibitor, Wortmannin, prior to rOPN to establish its neuroprotective mechanism. ELISA was used to measure rOPN delivery into the cerebrospinal fluid.

Results—Cerebrospinal fluid level of rOPN increased after its nasal administration. This was associated with improved neurological scores and reduced brain edema at 24 hours after SAH. rOPN increased phosphorylated FAK and phosphorylated Akt expressions and decreased caspase-3 cleavage, resulting in attenuation of neuronal cell death within the cerebral cortex. These effects were abolished by FAK inhibitor 14 and Wortmannin.

Conclusions—Nasal administration of rOPN decreased neuronal cell death and brain edema and improved the neurological status in SAH rats, possibly through FAK–phosphatidylinositol 3-kinase–Akt–induced inhibition of capase-3 cleavage.