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Increased expression of caspase 2 in experimental and human temporal lobe epilepsy

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Abstract

Temporal lobe epilepsy (TLE) is often caused by a neurodegenerative brain insult that triggers epileptogenesis, and eventually results in spontaneous seizures, i.e., epilepsy. Understanding the mechanisms of cell death is a key for designing new drug therapies for preventing the neurodegeneration associated with TLE. Here, we investigated the expression of caspase 2, a protein involved in programmed cell death, during the course of epilepsy. We investigated caspase 2 expression in hippocampal samples derived from patients operated on for drug refractory TLE. To understand the evolution of altered-caspase 2 expression during the epileptic process, we also examined caspase 2 expression and activity in the rat hippocampus after status epilepticus-induced acute damage, during epileptogenesis, and after the onset of epilepsy. Caspase 2 expression was enhanced in the hippocampal neurons in chronic TLE patients. In rats, status epilepticus-induced caspase 2 labeling paralleled the progression of neurodegeneration. Proteolytic activation and cleavage of caspase 2 was also detected in the rat brain undergoing epileptogenesis. Our data suggest that caspase 2-mediated programmed cell death participates in the seizure-induced degenerative process in experimental and human TLE.

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Authors and Affiliations

  1. A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, PO Box 1627, FIN-70 211, Kuopio, Finland

    Susanna Narkilahti & Asla Pitkänen

  2. Regea Institute for Regenerative Medicine, University of Tampere, Biokatu 12, FI-33520, Tampere

    Susanna Narkilahti

  3. Department of Neurology, Kuopio University Hospital, PO Box 1777, FIN-70 211, Kuopio, Finland

    Leena Jutila, Reetta Kälviäinen & Asla Pitkänen

  4. Department of Pathology, Kuopio University Hospital, PO Box 1777, FIN-70 211, Kuopio, Finland

    Irina Alafuzoff & Leo Paljärvi

  5. Department of Pathology and Forensic Medicine, Kuopio University Hospital, PO Box 1777, FIN-70 211, Kuopio, Finland

    Kari Karkola

  6. Department of Pathology, Laboratory Centre, Tampere University Hospital, PO Box 2000, FI-33521, Tampere, Finland

    Leo Paljärvi

  7. Department of Neurosurgery, Kuopio

    Arto Immonen & Matti Vapalahti

  8. Department of Clinical Neurophysiology University Hospital, PO Box 1777, FIN-70 211, Kuopio, Finland

    Esa Mervaala

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  1. Susanna Narkilahti
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  2. Leena Jutila
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Correspondence to Susanna Narkilahti.

Additional information

The work was supported by The Academy of Finland, The Kuopio University Foundation, The Neurology Foundation, The North-Savo Regional Fund of the Finnish Cultural Foundation, Sigrid Juselius Foundation, and The Vaajasalo Foundation.

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Narkilahti, S., Jutila, L., Alafuzoff, I. et al. Increased expression of caspase 2 in experimental and human temporal lobe epilepsy. Neuromol Med 9, 129–144 (2007). https://doi.org/10.1007/BF02685887

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