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Stimulation of β2-Adrenoceptors Induces Nerve Growth Factor and Inhibits Apoptosis in Rat Brain After Ischemia

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Maturation Phenomenon in Cerebral Ischemia III

Summary

Stimulation of β2-adrenoceptors in primary mixed cultures of rat hippocampai cells clearly protects neurons against glutamate-induced damage by an increased expression of nerve growth factor (NGF), since the neuroprotective effect of clenbuterol, a β2-adrenergic drug, was abolished, or at least reduced, by a β-blocker, NGF antibodies, p75 antibodies and NGF antisense oligodeoxynucleotide (ODN). Clenbuterol also reduced the infarct volume after occlusion of the middle cerebral artery in the rat and it decreased the number of damaged neurons after 10 min forebrain ischemia in the CA1 subfield of the rat. Simultaneously, the synthesis of NGF, as well as the synthesis of basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF-β1), was upregulated in various regions of the brain. In the rat model of global forebrain ischemia, DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells were diminished by clenbuterol, suggesting an anti-apoptotic potency of this drug. In addition, we could demonstrate an upregulation of the anti-apoptotic oncogenes Bcl-2 and Bcl-xl caused by clenbuterol, an effect, which could also contribute to the neuroprotection caused by stimulation of β2adrenoceptors.

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Authors
  1. J. Krieglstein
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  2. C. Culmsee
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  3. Y. Zhu
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  4. I. Semkova
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Editor information

Editors and Affiliations

  1. Department of Neurosurgery, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino-shi, Tokyo 180, Japan

    Umeo Ito

  2. Dipartimenti di Scienze Neurologiche, Università di Roma “La Sapienza”, Viale dell’University 30, 00185, Roma, Italy

    Cesare Fieschi

  3. Istituto Neurologico Mediterraneo, NEUROMED Research Laboratories, Via Atinense 18, 86077, Pozzilli (Isernia), Italy

    Francesco Orzi

  4. Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113 Tokyo, Japan

    Toshihiko Kuroiwa

  5. National Institutes of Health, Laboratory of Neuropathology and Neuroanatomical Sciences, NINDS, Bethesda, MD, 20892-4128, USA

    Igor Klatzo

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© 1999 Springer-Verlag Berlin Heidelberg

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Krieglstein, J., Culmsee, C., Zhu, Y., Semkova, I. (1999). Stimulation of β2-Adrenoceptors Induces Nerve Growth Factor and Inhibits Apoptosis in Rat Brain After Ischemia. In: Ito, U., Fieschi, C., Orzi, F., Kuroiwa, T., Klatzo, I. (eds) Maturation Phenomenon in Cerebral Ischemia III. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58602-6_10

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  • DOI: https://doi.org/10.1007/978-3-642-58602-6_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65023-2

  • Online ISBN: 978-3-642-58602-6

  • eBook Packages: Springer Book Archive

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