Temporal profile of neuronal damage in a model of transient forebrain ischemia

Authors

  • Dr. William A. Pulsinelli MD, PhD.,

    Corresponding author
    1. The Department of Medical Research Council Laboratories, Carshalton, Surrey, SM5 4EF, United Kingdom
    • The Department of Medical Research Council Laboratories, Carshalton, Surrey, SM5 4EF, United Kingdom
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  • James B. Brierley MD,

    1. The Department of Medical Research Council Laboratories, Carshalton, Surrey, SM5 4EF, United Kingdom
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  • Fred Plum MD

    1. Department of Neurology, Cornell University Medical College, 1300 York Ave, New York, NY 10021
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Abstract

This study examined the temporal profile of ischemic neuronal damage following transient bilateral forebrain ischemia in the rat model of four-vessel occlusion. Wistar rats were subjected to transient but severe forebrain ischemia by permanently occluding the vertebral arteries and 24 hours later temporarily occluding the common carotid arteries for 10, 20, or 30 minutes. Carotid artery blood flow was restored and the rats were killed by perfusion-fixation after 3, 6, 24, and 72 hours. Rats with postischemic convulsions were discarded. Ischemic neuronal damage was graded in accordance with conventional neuropathological criteria. Ten minutes of four-vessel occlusion produced scattered ischemic cell change in the cerebral hemispheres of most rats. The time to onset of visible neuronal damage varied among brain regions and in some regions progressively worsened with time. After 30 minutes of ischemia, small to medium-sized striatal neurons were damaged early while the initiation of visible damage to hippocampal neurons in the h1 zone was delayed for 3 to 6 hours. The number of damaged neurons in neocortex (layer 3, layers 5 and 6, or both) and hippocampus (h1, h3–5, paramedian zone) increased significantly (p < 0.01) between 24 and 72 hours. The unique delay in onset of ischemic cell change and the protracte increase in its incidence between 24 and 72 hours could reflect either delayed-appearance of ischemic change in previously killed neurons or a delayed insult that continued to jeopardize compromised but otherwise viable neurons during the postischemic period.

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