title: Distinctive neuropathologic alterations in the deep layers of the parietal cortex after moderate ischemic-hypoxic injury in the P3 immature rat brain.
abstract: Moderate focal brain hypoxic-ischemic (HI) injury in the immature P3 rat leads to loss of cortical volume and disruptions of cortical myelination. In this study, we characterized the time course and pattern of cellular degeneration, axonal disruption, astrogliosis, and microglia activation. After moderate transient unilateral hypoxia-ischemia, brains were collected at set time points and positive staining was assessed. Cellular degeneration stained with Fluoro-Jade B (FJ-B) was distributed in a columnar pattern, primarily within the deep cortical layers V-VII extending up to layer IV of the parietal cortex (pCx). FJ-B staining increased in the ipsilateral pCx 12 and 24 h (p < 0.05) after the injury. Beta-amyloid precursor protein immunoreactivity indicating axonal disruption increased at 24 h (p < 0.05) and showed the same distribution as FJ-B. Glial fibrillary acidic protein-positive astrocytes increased dramatically within the ipsilateral pCx from 24 h (p < 0.05) to 18 d (p < 0.001) after HI injury and displayed a columnar pattern extending from the deep cortical layers to layers IV. Isolectin-B4 and ED1-labeled microglia were also increased within the ipsilateral deep pCx and underlying white matter between 12 and 24 h (p < 0.01), and increased Isolectin-B4 lasted up to 7 d after injury. These observations are consistent with the hypothesis that neuronal loss, astrogliosis, and microglia activation precede the subsequent disruption of cortical growth and myelination. This model offers new possibilities for investigating the cellular and molecular mechanisms of damage and repair after neonatal HI injury.
authors.affiliation: Unité de Dévelopment, Department of Pediatrics, University of Geneva, 1211 Geneva, Switzerland. stephane.sizonenko@medecine.unige.ch
authors.forename: Stéphane V
authors.initials: SV
authors.lastname: Sizonenko
authors.forename: Jozsef Z
authors.initials: JZ
authors.lastname: Kiss
authors.forename: Terrie
authors.initials: T
authors.lastname: Inder
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: Chris E
authors.initials: CE
authors.lastname: Williams
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology; D009930:Organic Chemicals; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling
chemical_list: D016564:Amyloid beta-Protein Precursor; D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D009930:Organic Chemicals; C435731:fluoro jade