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p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord

An immunohistochemical investigation in the rat

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Abstract

The possibility that serotonin may influence the early response of astrocytes around a spinal cord trauma was investigated in a rat model by making a unilateral incision into the right dorsal horn of the T10-11 segments. One group of rats received a serotonin synthesis inhibitor, p-chlorophenylalanine (p-CPA) before injury in doses which cause a depletion of serotonin in the cord. Another group of traumatised rats did not receive p-CPA. All animals were allowed to survive for 5 h. Samples for immunohistochemistry were taken from the T9, T10-11 and T12 segments of the cord. Paraffin sections were immunostained for glial fibrillary acidic protein (GFAP) using monoclonal antibodies and avidin-biotin complex technique. Trauma to the cord resulted in a marked increase of GFAP immunoreactivity in all the investigated segments, particularly in the ipsilateral side. Pretreatment with p-CPA markedly reduced the GFAP response. This drug did not by itself influence the GFAP immunoreactivity of the cord of untraumatised rats. Our results show that trauma to the spinal cord induces a rapid enhancement of GFAP immunoreactivity in the cord which is present even far away from the primary lesion. This response can be prevented by pretreatment with the serotonin synthesis inhibitor, p-CPA. The results indicate that serotonin influences the increase of GFAP immunoreactivity following spinal cord injury either directly or indirectly, for instance by its microvascular reactions.

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Authors and Affiliations

  1. Laboratory of Neuropathology, University Hospital, S-751 85, Uppsala, Sweden

    H. S. Sharma & Y. Olsson

  2. Institute of Neuropathology, Klinikum Steglitz, Free University Berlin, Hindenburgdamm 30, D-12200, Berlin, Germany

    H. S. Sharma & J. Cervós-Navarro

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  1. H. S. Sharma
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  2. Y. Olsson
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  3. J. Cervós-Navarro
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Supported by grants from the Swedish Medical Research Council projects no. 320, Trygg-Hansa, Söderbergs stiftelse, Hedlunds stiftelse, Swärds stiftelse, Thyrings stiftelse, RTP, Wallenius Line, Åhléns, Humboldt Foundation, Bonn, Germany and from the University Grants Commission, New Delhi, India

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Sharma, H.S., Olsson, Y. & Cervós-Navarro, J. p-Chlorophenylalanine, a serotonin synthesis inhibitor, reduces the response of glial fibrillary acidic protein induced by trauma to the spinal cord. Acta Neuropathol 86, 422–427 (1993). https://doi.org/10.1007/BF00228575

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  • DOI: https://doi.org/10.1007/BF00228575

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