Synthesis of Serotonin in Traumatized Rat Brain

Authors

  • K. Tsuiki,

    1. Cone Laboratory for Neurosurgical Research and
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    • The permanent address of Dr. K. Tsuiki is Department of Neurosurgery, Iwate Medical University, Morioka, Iwate, Japan.

  • A. Takada,

    1. Cone Laboratory for Neurosurgical Research and
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    • The permanent address of Drs. A. Takada and S. Nagahiro is Department of Neurosurgery, Kumamoto University Medical School, Kumamoto City, Kumamoto, Japan.

  • S. Nagahiro,

    1. Cone Laboratory for Neurosurgical Research and
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    • The permanent address of Drs. A. Takada and S. Nagahiro is Department of Neurosurgery, Kumamoto University Medical School, Kumamoto City, Kumamoto, Japan.

  • M. Grdiša,

    1. Cone Laboratory for Neurosurgical Research and
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    • The permanent address of Dr. M. Grdiša is Department of Molecular Medicine, Rudjeu Boškovic Institute, Zagreb, Croatia.

  • M. Diksic,

    1. Cone Laboratory for Neurosurgical Research and
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  • H. M. Pappius

    Corresponding author
    1. Goad Unit of the Donner Laboratory of Experimental Neurochemistry, Montreal Neurological Institute and Hospital, and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
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Address correspondence and reprint requests to Dr. H. M. Pappius at Montreal Neurological Institute, 3801 University St., Montreal, Quebec, Canada H3A 2B4.

Abstract

Abstract: Previous studies have demonstrated that focal freezing lesions in rats cause a widespread decrease of cortical glucose use in the lesioned hemisphere and this was interpreted as a reflection of depression of cortical activity. The serotonergic neurotransmitter system was implicated in these alterations when it was shown that (1) cortical serotonin metabolism was increased widely in focally injured brain and (2) inhibition of serotonin synthesis prevented the development of cortical hypometabolism. In the present studies we applied an autoradiographic method that uses the accumulation of the 14C-labeled analogue of serotonin α-methylserotonin to assess changes in the rate of serotonin synthesis in injured brain. The results confirmed that 3 days after the lesion was made, at the time of greatest depression of glucose use, serotonin synthesis was significantly increased in cortical areas throughout the injured hemisphere. The increase was also seen in the dorsal hippocampus and area CA3, as well as in the medial geniculate and dorsal raphe, but not in any other subcortical structures including median raphe. Present results suggest that the functional changes in the cortex of the lesioned hemisphere are associated with an increased rate of serotonin synthesis mediated by activation of the dorsal raphe. We also documented by α-[14C]aminoisobutyric acid autoradiography that there was increased permeability of the blood-brain barrier, but this was restricted to the rim of the lesion.

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