Different mechanisms may be responsible for neurocognitive deficit (NCD) following cardiac surgery, including immune activation due to cardiopulmonary bypass (CPB) and cerebral embolization. Short-term NCD following CPB was recently reported in a rat model [1]. We hypothesized that long-term NCD would occur in a similar set-up, and would be exacerbated by the injection of microspheres to simulate atheromatous embolization.

Methods and results
Male Wistar rats (c. 450g) were anaesthetized and subjected to one hour of CPB (n = 12) or sham-operated (n = 9). Twelve weeks after recovery, they were neurocognitively tested in the Morris Water Maze. Analysis using EthoVision showed no difference in the learning curve (decreasing search time or distance) between groups.

In a second experiment, either 30µm diameter microspheres (n = 12) [2] or vehicle (n = 4) was injected into the right internal carotid artery of similar rats. Again, the learning curves did not differ.

Using a new method to achieve bilateral distribution [3] in pilot experiments, there was a tendency for the injected animals (n = 5) to perform less well than control or sham-operated animals (n = 7).

Discussion
Injury due to CPB in the rat is either too minor to be detected, or the NCD does not persist beyond the short term. The plasticity of the rat brain may allow recovery from unilateral embolic damage, but bilateral damage appears to cause a lasting deficit. We intend to use this model to test possible pharmacological protective measures against surgery-induced NCD.

References

1. Mackensen, G.B.; Sato, Y.; Nellgard, B. et al. (2001). Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat. Anesthesiology, 95, 1485-1491.
2. Demura, N.; Mizukawa, K.; Ogawa, N.; et al. (1993). A cerebral ischemia model produced by injection of microspheres via the external carotid artery in freely moving rats. Neurosci. Res. (Ireland), 17, 23-30.
3. de Lange, F.; Houston, R.J.F.; Kalkman, C.J. (2002) Unilateral intracarotid injection of holmium microspheres to induce diffuse bilateral cerebral embolization in rats. ASA 2002 meeting abstract (accepted).

Paper presented at Measuring Behavior 2002 , 4^th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands

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