Surfactant reduction of cerebral infarct size and behavioral deficit in a rat model of cerebrovascular arterial gas embolism

Abstract

Gas embolism occurs commonly in cardiac and vascular surgery and decompression sickness. The goals of this study were to develop a new in vivo rat model of cerebrovascular arterial gas embolism and to determine the effects of exogenous surfactants on resultant brain infarct volume and accompanying long-term neurological dysfunction using the model. Unilateral cerebral arterial gas embolism was induced in Sprague Dawley rats, including groups receiving intravenous Pluronic F-127 (PF-127) and Oxycyte perflourocarbon surfactant pretreatment. Magnetic resonance imaging (MRI) was performed at 24 and 72 h postembolism to determine infarct volume. The elevated body swing test (EBST), limb-placement test, proprioception forelimb and hindlimb tests, whisker tactile test, and Morris Water Maze test were performed to assess motor behavior, somatosensory deficit, and spatial cognitive function out to 29 days after embolization. A stable stroke model was developed with MRI examination revealing infarction in the ipsilateral cerebral hemisphere. Gas embolized rats had significant cognitive and sensorimotor dysfunction, including approximately threefold increase in Morris Water Maze latency time, ∼20% left-sided biasing in EBST performance, 0.5 to 1.5 (mean) point score elevations in the proprioception and whisker tactile tests, and 3.0 point (mean) elevation in the limb-placement test, all of which were persistent throughout the postembolic period. Surfactant prophylaxis with either PF-127 or Oxycyte rendered stroke undetectable by MRI scanning and markedly reduced the postembolic deficits in both cognitive and sensorimotor performance in treated rats, with normalization of EBST and whisker tactile tests within 7 days.

Keywords: animal; behavior; cognition; experimental; gas embolism; rat; stroke; surfactant.

Fig. 1.

Magnetic resonance images at 24 h postoperatively for sham-operated (A), gas-embolized (B), gas-embolized plus PF-127-pretreated (C), and gas-embolized plus Oxycyte-pretreated (D) rats.

Fig. 2.

Infarct volume in the 6 gas-embolized (no surfactant prophylaxis) animals at 1 and 3 days after induction of injury.

Fig. 3.

Time course of results of Morris Water Maze latency period (A) and swimming speed (B). Data are shown as means + SD. P < 0.00625 compared with sham-operated controls for animals receiving vehicle + microbubbles (*), vehicle + microbubbles + PF-127 ($), and vehicle + microbubbles + Oxycyte (#). **P < 0.00625 compared with baseline within the same treatment group. ***P < 0.00625 compared with value at 3 days postoperative within the same treatment group, n = 6 animals per group.

Fig. 4.

Time course of results of elevated body swing (A) and limb-placement (B) behavioral tests. Data for elevated body swing test are shown as means + SD. P < 0.00625 compared with sham-operated controls for animals receiving vehicle + microbubbles (*), vehicle + microbubbles + PF-127 ($), and vehicle + microbubbles + Oxycyte (#). **P < 0.00625 compared with baseline within the same treatment group. ***P < 0.00625 compared with value at 3 days postoperative within the same treatment group. Data for limb-placement test are shown as box plots with a line within the box marking the median and the lower and upper boundaries of the box indicating the 25th and 75th percentiles, respectively. Differences are significant with P < 0.001 compared with sham-operated controls for animals receiving vehicle + microbubbles (^x), vehicle + microbubbles + PF-127 (S), and vehicle + microbubbles + Oxycyte (F). ^xxDifferences are significant with P < 0.001 compared with baseline within the same treatment group. ^xxxDifferences are significant with P < 0.001 compared with value at 3 days postoperative within the same treatment group, n = 6 animals per group.

Fig. 5.

Time course of results of the proprioception forelimb (A), proprioception hindlimb (B), and whisker-tactile (C) behavioral tests. Data are shown as box plots with a line within the box marking the median, and the lower and upper boundaries of the box indicating the 25th and 75th percentiles, respectively. Differences are significant with P < 0.001 compared with sham-operated controls for animals receiving vehicle + microbubbles (^x), vehicle + microbubbles + PF-127 (S), and vehicle + microbubbles + Oxycyte (F). ^xxDifferences are significant with P < 0.001 compared with baseline within the same treatment group. ^xxxDifferences are significant with P < 0.001 compared with value at 3 days postoperative within the same treatment group; n = 6 animals per group.