Bilateral changes after neonatal ischemia in the P7 rat brain

Maria Spiegler, Sonia Villapol, Valérie Biran, Catherine Goyenvalle, Jean Mariani, Sylvain Renolleau, Christiane Charriaut-Marlangue

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10 Scopus citations


Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and subgranular zone (SGZ) and increases in the adult after brain injury. In this study, postnatal day 7 rats underwent middle cerebral artery electrocoagulation and transient homolateral common carotid artery occlusion, a lesioning protocol that resulted in ipsilateral (IL) forebrain ischemic injury, leading to a cortical cavity 3 weeks later. The effects of neonatal ischemia on hemispheric damage, cell death, cell proliferation, and neurogenesis were examined 4 hours to 6 weeks later by the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and immunohistochemistry of Ki-67 in proliferating cells and of doublecortin, a microtubule-associated protein expressed only by immature neurons. Neonatal ischemic injury resulted in persistent reduced IL and transient reduced contralateral (CL) hemispheric areas, a consequence of sustained and transient cell death in the IL and CL areas, respectively. Ki-67 immunostaining revealed 3 peaks of newly generated cells in the dorsal SVZ and SGZ in the IL side and also in the CL side at 48 hours and 7 and 28 days after ischemia. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 hours. Ischemic injury also stimulated SVZ neurogenesis, based on increased doublecortin immunostaining in both SVZs at 7 to 14 days after injury. Doublecortin-positive neurons remained visible around the lesion at 21 days but displayed an immature shape in discrete chains or clusters. Although unilateral ischemic damage was produced, results indicate successful regenerative changes in the CL hemisphere, allowing anatomical recovery.

Original languageEnglish (US)
Pages (from-to)481-90
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
StatePublished - Jun 2007


  • Animals
  • Animals, Newborn
  • Brain
  • Brain Ischemia
  • Cell Death
  • Cell Proliferation
  • Female
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Ki-67 Antigen
  • Male
  • Microtubule-Associated Proteins
  • Nerve Regeneration
  • Neurons
  • Neuropeptides
  • Oligodendroglia
  • Rats
  • Time Factors
  • Journal Article


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