Toxicology of Industrial Compounds

244 NEUROTOXICITY TESTING OF INDUSTRIAL COMPOUNDS
Figure 18.2 Time-course of GFAP concentration in hippocampus by kainic acid. Rats
were treated with a single systemic dose of kainic acid (12 mg kg −1 , i.p.). GFAP was
determined by ELISA at the times indicated. Results are expressed as mean±SEM
(from Van den Berg and Gramsbergen, 1993, with permission).
time-course study, covering a period of 6 months, has indicated that in the
hippocampus a peak of 45 Ca uptake occurred already after 4 days and
normal values were reached only after another 2–4 months (Van den Berg
and Gramsbergen, 1993). More recent results indicate that other limbic
areas display similar kinetics, while 45 Ca uptake in striatum and cortex
return faster to normal values, e.g. within 2 weeks. Only in the thalamus a
long-term sustained 45 Ca uptake was present for a period of 6 months. In
general a good correlation was found between the regions showing
sustained 45 Ca accumulation and those known to be targets of KA
neurotoxicity. When these data on 45 Ca accumulation were related to
effects of KA on GFAP concentrations, also a good agreement was
observed concerning the brain regions involved (Gramsbergen and Van den
Berg, 1994). Histopathological examination of hippocampal sections
revealed extensive neurodegeneration by KA in CA1, CA3 and CA4
regions (Van den Berg and Gramsbergen, 1993).
Heavy metals
Lead may produce in children symptoms of acute encephalopathy after
exposure to high doses and at lower dose levels learning disorders and