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

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 (K_i) of ¹⁴C-α-aminoisobutyric acid (¹⁴C-AIB) was measured. Regional cerebral blood flow (rCBF), regional arteriolar and venular O₂ saturation (SaO₂ and SvO₂ respectively), and O₂ consumption were determined using ¹⁴C-iodoantipyrine autoradiography and cryomicrospectrophotometry in alternate slices of the brain tissue. The K _i of ¹⁴C-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 O ₂ consumption by hyperosmolar BBB disruption and attenuation of the increase with NMDA blockade without affecting the degree of BBB disruption.