Effects of blockade of NMDA receptors on cerebral oxygen consumption during hyperosmolar BBB disruption in rats

• Published in: Journal of the neurological sciences 2013-03, Vol.326 (1), p.29-34
• Main Authors: Chi, Oak Z, Barsoum, Sylviana, Grayson, Jeremy, Hunter, Christine, Liu, Xia, Weiss, Harvey R
• Format: Article
• Language: English
• Subjects: Animals; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiopathology; Blood–brain barrier; Brain - drug effects; Brain - physiopathology; Cerebral blood flow; Cerebral microcirculation; Cerebral oxygen consumption; Cerebral oxygen saturation; Excitatory Amino Acid Antagonists - pharmacology; Male; Neurology; NMDA; Oxygen Consumption - drug effects; Oxygen Consumption - physiology; Pipecolic Acids - pharmacology; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - physiology; Treatment Outcome
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2013.01.006

Abstract Hyperosmolar blood–brain barrier (BBB) disruption has been reported to increase cerebral O2 consumption. This study was performed to test whether blockade of N -methyl- d -aspartate (NMDA) receptor would affect cerebral O2 consumption during hyperosmolar BBB disruption. A competitive NMDA receptor antagonist CGS-19755 10 mg/kg was injected iv 15 min before intracarotid infusion of 25% mannitol. Twelve min after BBB disruption, the BBB transfer coefficient (Ki ) of14 C-α-aminoisobutyric acid (14 C-AIB) was measured. Regional cerebral blood flow (rCBF), regional arteriolar and venular O2 saturation (SaO2 and SvO2 respectively), and O2 consumption were determined using14 C-iodoantipyrine autoradiography and cryomicrospectrophotometry in alternate slices of the brain tissue. The Ki of14 C-AIB was markedly increased with hyperosmolar mannitol in both the control (5.8 ×) and the CGS treated rats (5.2 ×). With BBB disruption, the O2 consumption was significantly increased (+ 39%) only in the control but not in the CGS treated rats and was significantly lower (− 29%) in the CGS treated than the control rats. The distribution of SvO2 was significantly shifted to the higher concentrations with CGS treatment. Our data demonstrated an increase of O2 consumption by hyperosmolar BBB disruption and attenuation of the increase with NMDA blockade without affecting the degree of BBB disruption.