Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury

Elisa Roncati Zanier, Stefan M. Lee, Paul M. Vespa, Christopher C. Giza, David A. Hovda

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Abstract

This study was designed to determine whether a secondary increase in neuronal activity induced by a low dose of kainic acid (KA), a glutamate analogue, exacerbates the anatomical damage in hippocampal regions following a mild lateral fluid percussion (LFP) brain injury. KA (9 mg/kg) was injected intraperitoneally in LFP-injured rats (n = 16) 1 h post-trauma. The neuronal loss in the CA3, CA4, and hilar regions at 7 days was quantified by two-dimensional cell counts. Hippocampal activation 15 min following KA injection was assessed by measuring local glucose metabolic rates (ICMRglc). Following LFP+KA, the ipsilateral side exhibited a 62.7%, 75.7%, and 52.1% decrease in the number of CA3, CA4 and hilar neurons, respectively, compared to naive rats (n = 3). These CA3 and CA4 neuronal counts were also significantly decreased compared to LFP+saline (n = 5) and sham+KA (n = 9) groups. The median Racine Score, used to rate the severity of behavioral seizures, was 4 in LFP+KA and 2 in sham+KA groups (p <0.015), suggesting a reduction in seizure threshold following injury. ICMRglc in CA3 following LFP+KA was 121.8 ± 2.0 (mean ± SE) ipsilaterally and 71.5 ± 5.4 contralaterally (p <0.0012). No changes were found in the BBB permeability as measured by [14C]aminoisobutyric acid in CA3, CA4, and hilar regions. We conclude that the presence of low-level KA 1 h after LFP dramatically increases the extent of hippocampal activation and induces a striking loss of ipsilateral CA3 and CA4 pyramidal neurons. Neuronal excitation during a time of cellular vulnerability may trigger or amplify the cycle of secondary damage in functionally impaired, but potentially viable, tissue.

Original languageEnglish
Pages (from-to)409-420
Number of pages12
JournalJournal of Neurotrauma
Volume20
Issue number5
Publication statusPublished - May 1 2003

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Keywords

  • Kainic acid
  • Secondary injury
  • Seizures
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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