Age-Dependent Changes in Long-Term Seizure Susceptibility and Behavior After Hypoxia in Rats

Authors

  • F. E. Jensen,

    Corresponding author
    1. Department of Neurology Children's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.A.
      Address correspondence and reprint requests to Dr. F. E. Jensen at Department of Neurology, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, U.S.A.
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  • G. L. Holmes,

    1. Department of Neurology Children's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • C. T. Lombroso,

    1. Department of Neurology Children's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • H. K. Blume,

    1. Department of Neurology Children's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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  • I. R. Firkusny

    1. Department of Neurology Children's Hospital, and Harvard Medical School, Boston, Massachusetts, U.S.A.
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Address correspondence and reprint requests to Dr. F. E. Jensen at Department of Neurology, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, U.S.A.

Abstract

Summary: We showed that hypoxia is acutely epileptogenic in immature but not in adult rats. In the present study, we evaluated whether hypoxia results in an in-crease in long-term seizure susceptibility to flurothyl and whether this is associated with impaired performance on behavioral tests. We also determined whether these long-term outcomes are dependent on age at time of O2, deprivation. Long Evans hooded rats were rendered hypoxic on either postnatal day (P)5, P10, or P60. Sixty to 75 days after hypoxia, rats were tested for performance in water maze, open field, and handling tests and for seizure susceptibility to flurothyl. Hypoxia at P10 significantly in-creased seizure susceptibility to fluorothyl, whereas hypoxia at P5 and P60 induced no long-term changes in seizure threshold. At P10, greater seizure severity during hypoxia and more prolonged exposure to hypoxia significantly increased long-term seizure susceptibility. This long-term change in seizure susceptibility appeared to be dissociated from any long-term neurobehavioral consequences, because only animals rendered hypoxic as adults (P60) had impaired behavioral performance. The results suggest that hypoxia-induced seizures can alter long-term seizure susceptibility and that this long-term effect is dependent on age and on severity of seizure activity at the time of previous hypoxia.

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