TY - JOUR
T1 - Increased hippocampal CA3 vulnerability to low-level kainic acid following lateral fluid percussion injury
AU - Zanier, Elisa Roncati
AU - Lee, Stefan M.
AU - Vespa, Paul M.
AU - Giza, Christopher C.
AU - Hovda, David A.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
KW - Kainic acid
KW - Secondary injury
KW - Seizures
KW - Traumatic brain injury
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M3 - Article
C2 - 12803974
AN - SCOPUS:0037512500
VL - 20
SP - 409
EP - 420
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
SN - 0897-7151
IS - 5
ER -