Alzheimer Disease I

The cytokine interleukin-I (IL-I) and its endogenous antagonist (IL-I ra) have important functions in the central nervous system. Recent experimental observations have suggested that recombinant L-LRA (rL-Ira) has neuroprotective properties in ischaemia. excitotoxicity, and trauma. We wished to see what effect rU-I ra had on kainic acid-induced neuronal death and to investigate how this might relate to changes in expression of the amyloid precursor protein gene (APP) and glial fibrillary acid protein (GFAP) using in situ hybridization. Wistar rats were treated by intraccrebroventricular administration with rUIra at doses of 10, 20 and 40 pg given ten minutes befort and 10 minutes after inuapritoneal kainic acid 10 mgkg. Behaviour was measured and, after LO days, the brains were removed for histology and in situ hybridization. There were no anticonvulsant effects on kainic acid-induced wet dog shakes or limbic motor s e i m s with rIL-1 ra af any dose tested. With rIL-I ra 10 pg given twice, there was si,&cant protection of neurons in the CAI field of the hippocampus and dorsal thalamus, but not in the primary olfactory cortex-amygdaloid region. Small, but insignificant. neuroprotective effects were observed in the Same anatomical regions with a dose of 20 pg given twice. and no neuroprotective effects were observed with 40 pg. The enhaccd neuronal survival in CAI and the dorsal thalamus was associated with preservation of APP 695 MRNA neumnal form) and lack of stimulation of both APP 770 (glial form) and GFAP mcssages, used as a measure of astrocyte activation. Where there was no neuroprotection APP 695 MRNA was reduced and stimulation of both APP 770 and GFAP mRNAs was observed. In conclusion. rIL-1 RA bas doseand regiondependent effects on neuronal survival after kainic acid and prevents damage-induced changes in APP and GFAP mRiiAs. P1 .D1.02 Human p-Amyloid Deposition in Brain and Extracerebral Tissues after Cardiac Arrest in Rats with Short-Term Siirvival R.Pluta, M.Barcikowska, S.Januszewski, A.Misicka and A. W. Lipkowski Medical Research Centre, PAS, Warsaw, Poland