Neuropathogical features of a rat model for perinatal hypoxic-ischemic encephalopathy with associated epilepsy

Authors

  • Shilpa D. Kadam,

    1. Department of Biomedical Sciences, Neurosciences Division, Colorado State University, Fort Collins, Colorado 80523, and Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah 84108
    Current affiliation:
    1. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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  • F. Edward Dudek

    Corresponding author
    1. Department of Biomedical Sciences, Neurosciences Division, Colorado State University, Fort Collins, Colorado 80523, and Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah 84108
    • Department of Physiology, University of Utah School of Medicine, 420 Chipeta Way, Suite 1700, Salt Lake City, UT 84108
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Abstract

Hypoxic-ischemic (HI) encephalopathy is an important neurological problem of the perinatal period. Little is known of the long-term progression of HI insults or the maladaptive changes that lead to epilepsy. Using rats with unilateral carotid occlusion followed by hypoxia at postnatal day 7, this study provides an initial analysis of the epilepsy caused by a perinatal HI insult with chronic and continuous behavioral monitoring. The histopathology was investigated at postnatal day 30 and later at ≥6 months of age using cresyl violet, Timm, and rapid Golgi staining and immunocytochemistry. The resultant epilepsy showed an increase in seizure frequency over time, with a preponderance for seizure clusters and behavioral features of an ipsilateral cerebral syndrome. In addition to parasagittal infarcts and porencephalic cysts in severe lesions, columnar neuronal death was found with cytomegaly in isolated groups of dysmorphic cortical neurons. Cortical dysgenesis was seen in the form of deep laminar cell loss, microgyri, white matter hypercellularity, and blurring of the white and gray matter junction. Mossy fiber sprouting was not only detected in the atrophied ipsilateral dorsal hippocampus of HI rats with chronic epilepsy, but was also found in comparable grades in spared ipsi- and contralateral ventral hippocampi. The cortical lesions in this animal model show histological similarities with those found in humans after perinatal HI. The occurrence of cortical abnormalities that are associated with epilepsy in humans correlates with the consequent detection of spontaneous recurrent seizures. J. Comp. Neurol. 505:716–737, 2007. © 2007 Wiley-Liss, Inc.

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