Protective effects of tirilazad mesylate and metabolite U-89678 against blood-brain barrier damage after subarachnoid hemorrhage and lipid peroxidative neuronal injury

Journal of Neurosurgery
S L SmithE D Hall

Abstract

The 21-aminosteroid lipid-peroxidation inhibitor, tirilazad mesylate (U-74006F), recently was shown in a large multinational Phase III clinical trial to decrease mortality and improve neurological recovery in patients 3 months after onset of aneurysmal subarachnoid hemorrhage (SAH). A major tirilazad metabolite in animals and man, U-89678 is formed when the 4-5 double bond in the A-ring is reduced and has been postulated to contribute significantly to tirilazad's neuroprotective effects. In the first experiment of the present study, the authors compared the effects of tirilazad and U-89678 on acute blood-brain barrier (BBB) damage in rats subjected to SAH via injection of 300 microliters of autologous nonheparinized blood under the dura of the left cortex. The rats were treated by intravenous administration of either 0.3 or 1.0 mg/kg of tirilazad or U-89678 10 minutes before and 2 hours after SAH, and BBB damage was quantified according to the extravasation of the protein-bound Evans' blue dye into the injured cortex 3 hours post-SAH. The results revealed that 0.3 and 1.0 mg/kg tirilazad significantly reduced SAH-induced BBB damage 35.2% (p < 0.05) and 60.6% (p < 0.0001), respectively, in comparison to treatment with vehicle. T...Continue Reading

References

Mar 1, 1989·Stroke; a Journal of Cerebral Circulation·M Zuccarello, D K Anderson
Feb 1, 1987·The Journal of Clinical Investigation·S M SadrzadehJ W Eaton
Jan 1, 1986·Central Nervous System Trauma : Journal of the American Paralysis Association·H A Kontos, J T Povlishock
Jan 1, 1982·Acta neurochirurgica·T Trojanowski
May 1, 1982·Stroke; a Journal of Cerebral Circulation·T ShigenoJ Cervoś-Navarro
Nov 17, 1994·Annals of the New York Academy of Sciences·E D HallF F Sun
Apr 1, 1994·Postgraduate Medical Journal·A J Larner
Feb 1, 1994·Pharmaceutical Research·J C FleishakerG R Peters
Feb 1, 1993·Journal of Neurochemistry·E D HallP A Yonkers

❮ Previous
Next ❯

Citations

Apr 29, 1999·International Journal of Radiation Oncology, Biology, Physics·D KondziolkaL D Lunsford
Sep 22, 1999·Pathology Oncology Research : POR·R DurmazE Tel
Jun 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Peter WilfN Rubén Cúneo
Feb 11, 2014·Translational Stroke Research·Michael K Tso, R Loch Macdonald
Jun 9, 2006·Neurological Research·Fatima A Sehba, Joshua B Bederson
Sep 28, 2006·Proceedings. Biological Sciences·John L Maron, Elizabeth Crone
Feb 6, 2016·Journal of Pharmaceutical and Biomedical Analysis·P GadgilD S-L Chow
Nov 22, 2011·World Neurosurgery·Robert G WhitmoreSherman C Stein
Nov 3, 2004·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Erkan KaptanogluEtem Beskonakli
Sep 27, 2007·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·S L SmithE D Hall
Dec 14, 2005·Journal of the Neurological Sciences·Christian BermuellerStefan Zausinger
Jul 15, 2015·Neurochemical Research·Pooja Khanna SoodBimla Nehru
Jan 19, 2013·Journal of Neurotrauma·Ming SunYazhuo Zhang
Oct 4, 2016·Molecular Neurobiology·Rongrong ZhangXinyue Qin
Sep 1, 2004·Neurosurgery·Stefan ZausingerRobert Schmid-Elsaesser
Feb 26, 2009·Free Radical Research·Pamela B L PunShabbir Moochhala
Jun 19, 1998·Neurosurgery·R L MacdonaldP K Andrus

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.