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The Protective Effect of Dexanabinol (HU-211) on Nitric Oxide and Cysteine Protease-Mediated Neuronal Death in Focal Cerebral Ischemia

Neurochemical Research volume 33, pages 1683–1691 (2008)Cite this article

Abstract

We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p < 0.05). Dexanabinol treatment reduced NO concentration and cathepsin activity to the control level (p > 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p < 0.05). However, dexanabinol treatment lowered both of these (p < 0.05). We conclude that dexanabinol might be a useful agent for the treatment of stroke patients.

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Author information

Affiliations

  1. Department of Neurosurgery, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey

    Ramazan Durmaz

  2. Department of Anatomy, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey

    Hilmi Özden

  3. Department of Biochemistry, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey

    Güngör Kanbak, Okan Can Arslan & Kazım Kartkaya

  4. Department of Histology-Embryology, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey

    Erinç Aral

  5. Department of Physiology, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey

    Kubilay Uzuner

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  1. Ramazan Durmaz
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  2. Hilmi Özden
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Correspondence to Ramazan Durmaz.

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Durmaz, R., Özden, H., Kanbak, G. et al. The Protective Effect of Dexanabinol (HU-211) on Nitric Oxide and Cysteine Protease-Mediated Neuronal Death in Focal Cerebral Ischemia. Neurochem Res 33, 1683–1691 (2008). https://doi.org/10.1007/s11064-008-9605-0

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  • DOI: https://doi.org/10.1007/s11064-008-9605-0

Keywords

  • Apoptosis
  • Cathepsins
  • Dexanabinol
  • Nitric oxide
  • Permanent middle cerebral artery occlusion
  • TUNEL staining