title: Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury.
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 (lCMR(glc)). 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. lCMRglc 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 [(14)C]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.
authors.affiliation: Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Elisa Roncati
authors.initials: ER
authors.lastname: Zanier
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Lee
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vespa
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Giza
authors.forename: David A
authors.initials: DA
authors.lastname: Hovda
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D002452:Cell Count; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications*
chemical_list: D018690:Excitatory Amino Acid Agonists; D005947:Glucose; D007608:Kainic Acid