title: Cerebral Vasoactivity and Oxygenation with Oxygen Carrier M101 in Rats.
abstract: The severity of traumatic brain injury (TBI) may be reduced if oxygen can be rapidly provided to the injured brain. This study evaluated if the oxygen-carrier M101 causes vasoconstricton of pial vasculature in healthy rats (Experiment 1) and if M101 improves brain tissue oxygen (PbtO2) in rats with controlled cortical impact (CCI)-TBI (Experiment 2). M101 (12.5 mL/kg intravenous [IV] over 2 h) caused a mild (9 mm Hg) increase in the mean arterial blood pressure (MAP) of healthy rats without constriction of cerebral pial arterioles. M101 (12 mL/kg IV over 1 h) caused a modest (27 mm Hg) increase in MAP (peak, 123 ± 5 mm Hg [mean ± standard error of the mean]) of CCI-TBI rats and restored PbtO2to near pre-injury levels. In both M101 and untreated control (NON) groups, PbtO2was ∼30 ± 2 mm Hg pre-injury and decreased (p ≤ 0.05) to ∼16 ± 2 mm Hg 15 min after CCI. In NON, PbtO2remained ∼50% of baseline but M101 administration resulted in a sustained increase in PbtO2(peak, 25 ± 5 mm Hg), which was not significantly different from pre-injury until the end of the study, when it decreased again below pre-injury (but was still higher than NON). Histopathology showed no differences between groups. In conclusion, M101 increased systemic blood pressures without concurrent cerebral pial vasoconstriction (in healthy rats) and restored PbtO2to 86% of pre-injury for at least 80 min when given soon after CCI-TBI. M101 should be evaluated in a clinically-relevant large animal model for pre-hospital treatment of TBI.
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Paula
authors.initials: P
authors.lastname: Moon-Massat
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Saad Habib-E-Rasul
authors.initials: SH
authors.lastname: Mullah
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Rania
authors.initials: R
authors.lastname: Abutarboush
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Biswajit K
authors.initials: BK
authors.lastname: Saha
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Georgina
authors.initials: G
authors.lastname: Pappas
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.
authors.forename: Charles
authors.initials: C
authors.lastname: Auker
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.|2 Department of Surgery, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Richard M
authors.initials: RM
authors.lastname: McCarron
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.|2 Department of Surgery, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Francoise
authors.initials: F
authors.lastname: Arnaud
authors.affiliation: 1 Department of Neurotrauma, Naval Medical Research Center , Operational and Undersea Medicine Directorate, Silver Spring, Maryland.|2 Department of Surgery, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Anke
authors.initials: A
authors.lastname: Scultetus
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006454:Hemoglobins
keywords: brain; hemoglobin-based oxygen carrier; oxygen therapeutic; trauma; vascular reactivity