Acute neuroprotection to pilocarpine-induced seizures is not sustained after traumatic brain injury in the developing rat

Gene G Gurkoff, C. C. Giza, D. Shin, S. Auvin, R. Sankar, D. A. Hovda

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Following CNS injury there is a period of vulnerability when cells will not easily tolerate a secondary insult. However recent studies have shown that following traumatic brain injury (TBI), as well as hypoxic-ischemic injuries, the CNS may experience a period of protection termed "preconditioning." While there is literature characterizing the properties of vulnerability and preconditioning in the adult rodent, there is an absence of comparable literature in the developing rat. To determine if there is a window of vulnerability in the developing rat, post-natal day 19 animals were subjected to a severe lateral fluid percussion injury followed by pilocarpine (Pc)-induced status epilepticus at 1, 6 or 24 h post TBI. During the first 24 h after TBI, the dorsal hippocampus exhibited less status epilepticus-induced cell death than that normally seen following Pc administration alone. Instead of producing a state of hippocampal vulnerability to activation, TBI produced a state of neuroprotection. However, in a second group of animals evaluated 20 weeks post injury, double-injured animals were statistically indistinguishable in terms of seizure threshold, mossy fiber sprouting and cell survival when compared to those treated with Pc alone. TBI, therefore, produced a temporary state of neuroprotection from seizure-induced cell death in the developing rat; however, this ultimately conferred no long-term protection from altered hippocampal circuit rearrangements, enhanced excitability or later convulsive seizures.

Original languageEnglish (US)
Pages (from-to)862-876
Number of pages15
JournalNeuroscience
Volume164
Issue number2
DOIs
StatePublished - Dec 1 2009

Keywords

  • hippocampus
  • long-term outcome
  • preconditioning
  • secondary insult
  • vulnerability

ASJC Scopus subject areas

  • Neuroscience(all)

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