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Lesioning of the inferior olive using a ventral surgical approach

Characterization of temporal and spatial astrocytic responses at the lesion site and in cerebellum

  • Original Articles
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Molecular and Chemical Neuropathology

Abstract

Activated astrocytes, intrinsic components of both local and remote (axonal target regions) central nervous system injury responses, are now recognized as active metabolic and regulatory mediators in many neurological disorders. To further define these responses, we devised a new ventral surgical approach to unilaterally lesion the inferior olivary nuclear complex, which has a single predominant remote target, the cerebellum. Activated astrocyte number, volume, and density, as well as the total volume of brainstem involved in the astrocytic response, all peaked at postlesion day (pld) 4, returning toward, but not to, unoperated control values at pld 24 (p<0.05). In contrast, the peak astrocyte response in the cerebellum was delayed, being greatest at pld 6 (p<0.05 compared to control or pld 2). These responses were associated with increases in overexpression of S100β, an astrocyte-derived neurite growth factor, and with an increase in cerebellar steady-state levels of a neuronal injury response protein, the β-amyloid precursor protein (β-APP). This is similar to correlated increases in these two proteins that are found in epilepsy and alzheimer disease. Our studies defining remote astrocytic and neuronal responses may be important for understanding glialneuronal mechanisms underlying the spread of neuropathological changes in conditions such as Alzheimer disease.

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Authors and Affiliations

  1. Department of Medicine, University of Arkansas for Medical Sciences, 4300 West Seventh St., 72205, Little Rock, AR

    Kazuhiro Ito & W. Sue T. Griffin

  2. Department of Anatomy, University of Arkansas for Medical Sciences, 4300 West Seventh St., 72205, Little Rock, AR

    Kazuhiro Ito, Yasunari Ishikawa, Robert D. Skinner, Robert E. Mrak & W. Sue T. Griffin

  3. Department of Pathology, University of Arkansas for Medical Sciences, 4300 West Seventh St., 72205, Little Rock, AR

    Robert E. Mrak

  4. Department of Veterans' Affairs Medical Center, GRECC, John L. McClellan Memorial Veterans' Hospital, 4300 West Seventh St., 72205, Little Rock, AR

    Robert E. Mrak & W. Sue T. Griffin

  5. Department of Neurosurgery, University of The Ryukyus School of Medicine, Okinawa, Japan

    Kazuhiro Ito, Yasunari Ishikawa & Jiro Mukawa

  6. Departments of Neurology and Biochemsitry, University of Texas Southwestern Medical Center, Dallas, TX

    Marcelle Morrison-Bogorad

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  1. Kazuhiro Ito
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  2. Yasunari Ishikawa
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  3. Robert D. Skinner
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  6. Jiro Mukawa
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  7. W. Sue T. Griffin
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Ito, K., Ishikawa, Y., Skinner, R.D. et al. Lesioning of the inferior olive using a ventral surgical approach. Molecular and Chemical Neuropathology 31, 245–264 (1997). https://doi.org/10.1007/BF02815128

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  • DOI: https://doi.org/10.1007/BF02815128

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