Functional integration of new neurons into hippocampal networks and poststroke comorbidities following neonatal stroke in mice

S. D. Kadam, C. L. Smith-Hicks, D. R. Smith, P. F. Worley, A. M. Comi

Research output: Contribution to journalArticle

Abstract

Stroke in the developing brain is an important cause of chronic neurological morbidities including neurobehavioral dysfunction and epilepsy. Here, we describe a mouse model of neonatal stroke resulting from unilateral carotid ligation that results in acute seizures, long-term hyperactivity, spontaneous lateralized circling behavior, impaired cognitive function, and epilepsy. Exploration-dependent induction of the immediate early gene Arc (activity-regulated cytoskeleton associated protein) in hippocampal neurons was examined in the general population of neurons versus neurons that were generated ~ 1 week after the ischemic insult and labeled with bromodeoxyuridine. Although Arc was inducible in a network-specific manner after severe neonatal stroke, it was impaired, not only in the ipsilateral injured but also in the contralateral uninjured hippocampi when examined 6 months after the neonatal stroke. Severity of both the stroke injury and the acquired poststroke epilepsy negatively correlated with Arc induction and new neuron integration into functional circuits in the injured hippocampi.

Original languageEnglish (US)
Pages (from-to)344-357
Number of pages14
JournalEpilepsy and Behavior
Volume18
Issue number4
DOIs
StatePublished - Aug 2010

Keywords

  • Arc
  • Behavioral comorbidities
  • Epilepsy
  • Hyperactivity
  • Lateralized circling
  • Neonatal stroke
  • Open-field test
  • Timm stain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

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