Progressive neurodegeneration after intracerebroventricular kainic acid administration in rats: implications for schizophrenia?
BACKGROUND
Intracerebroventricular (ICV) administration of kainic acid to rats produces limbic-cortical neuronal damage that has been compared to the neuropathology of schizophrenia.


METHODS
Groups of adult rats were administered ICV kainic acid and then assessed for neuronal loss and the expression of proteins relevant to mechanisms of neuronal damage after one and fourteen days. Neuronal loss was assessed by two-dimensional cell counting and protein expression was assessed by immunohistochemistry.


RESULTS
ICV kainic acid administration was associated with both immediate (day 1) and delayed (day 14) neuronal loss in the dorsal hippocampus. The immediate injury was largely limited to the CA3 hippocampal subfield, while the delayed injury included the CA1 subfield. Multiple mechanisms of cell death appeared to be involved in the delayed neuronal loss, as evidenced by changes in the expression of glutamate receptor subunits, heat shock protein and jun protein.


CONCLUSIONS
ICV kainic acid administration to adult rats produces progressive damage to limbic-cortical neurons, involving both fast and slow mechanisms of cell death. Given the evidence for clinical deterioration, cognitive deficits and hippocampal neuropathy in some cases of schizophrenia, this animal model may be relevant for hypotheses regarding mechanisms of neurodegeneration in that disorder.
Csernansky
J G
JG
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Csernansky
C A
CA
Kogelman
L
L
Montgomery
E M
EM
Bardgett
M E
ME
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008032:Limbic System / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced*; D051381:Rats; D012559:Schizophrenia / Q000209:etiology*; D013997:Time Factors
D007608:Kainic Acid