title: Early NO-donor treatment improves acute perfusion deficit and brain damage after experimental subarachnoid hemorrhage in rats.
abstract: A lack of nitric oxide (NO) may be a possible factor in the pathogenesis of an acute decrease of cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether early therapy with an NO-donor can improve CBF and offer neuroprotection after experimental SAH in rats. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated with 1.5μg/kg/min of intravenous sodium nitroprusside (SNP) or vehicle (n=10) starting 15min after induction of SAH until 180min thereafter. SNP caused a moderate decrease of arterial blood pressure and cerebral perfusion pressure. Conversely, CBF measured by laser-Doppler flowmetry increased significantly in SNP-treated animals. The rate of injured neurons in the hippocampal CA1-field was significantly reduced in SNP-treated animals (10.5±5%) compared to controls (14.2±7%), as well as the number of Caspase-3 positive neurons. Low-dose treatment with SNP can attenuate an early perfusion deficit after SAH and reduce neuronal damage in spite of a hypotensive side effect. This may reflect the reversal of an early NO-deficit. In the clinical setting, the moderate hypotensive effect may be welcome since SAH-patients frequently present with elevated blood pressure.
authors.affiliation: Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lilla
authors.affiliation: Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hartmann
authors.affiliation: Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koehler
authors.affiliation: Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Ralf-Ingo
authors.initials: RI
authors.lastname: Ernestus
authors.affiliation: Department of Neurosurgery, University Hospital Wuerzburg, 97080 Wuerzburg, Germany. Electronic address: Westermaier.T@ukw.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Westermaier
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D007427:Intracranial Pressure / Q000187:drug effects / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009599:Nitroprusside / Q000008:administration & dosage*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D009599:Nitroprusside; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Acute vasospasm; CBF; Neuroprotection; Nitric oxide; Subarachnoid hemorrhage