Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury.
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.
Zanier
Elisa Roncati
ER
Brain Injury Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Lee
Stefan M
SM
Vespa
Paul M
PM
Giza
Christopher C
CC
Hovda
David A
DA
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*
D018690:Excitatory Amino Acid Agonists; D005947:Glucose; D007608:Kainic Acid