A CEREBRAL-ISCHEMIA MODEL PRODUCED BY INJECTION OF MICROSPHERES VIA THE EXTERNAL CAROTID-ARTERY IN FREELY MOVING RATS

We produced an improved microembolism model of cerebral focal ischemia by injection of 1000-2000 microspheres 50 (+/- 5 mum diameter) via a tube retrogradely inserted into the right external carotid artery in freely moving rats. The group injected with 2000 spheres showed a much more severe mortality rate as well as neurological signs than did the 1000-sphere group. Brain water content of the 2000-sphere group was examined and found to show an increase from 4 to 24 h after embolization in the right hemisphere, indicating serious brain edema. Severe neurological signs and individual deaths by embolization were most likely related to the extent of development of brain edema. Examination of learning behavior by shuttle-box avoidance revealed partial but significant impairment of learning in the 1000-sphere group. Autoradiographic studies for muscarinic acetylcholine receptors and protein kinase C binding sites were conducted. Both these binding sites decreased in number, but protein kinase C seems to be more susceptible to ischemic injury than muscarinic acetylcholine receptors. The observation was considered to be closely related with an impairment of learning. The present study suggests that our microembolism model in freely moving rats is useful for investigations of the early phase and late phase of cerebral ischemia.