Rational and Aims - Reduced CA3-driven interictal activity has been reported in hippocampal-entorhinal cortex (EC)-slices obtained from pilocarpine-treated rodents during 4-aminopyridine (4AP) treatment. In addition, ictal discharges initiating in EC persist throughout the experiment in these slices, while they disappear within the first 2 hours of 4AP superfusion in non-epileptic control (NEC) tissue. This evidence has led us to hypothesize that CA3 cell damage, which is known to occur in several models of mesial temporal lobe epilepsy (MTLE), may release EC ictogenesis. However, this in vitro data could also be related to the artificial condition set to record seizure activity in the slice. We addressed this issue by determining in vivo the extent of hippocampal network activation by using a marker sensitive to repetitive seizure activity: ΔFosB. Methods – We induced status epilepticus (SE) in Sprague-Dawley male rat by injecting pilocarpine i.p. (380 mg/kg). The animals where then sacrificed at 1, 3, 7, 14, 21 days and processed for ΔFosB immunodetection and other histopathological studies; alternatively, at 21 days they were used for in vitro analysis of the hippocampal-entorhinal cortex slice by intrinsic optical signal detection after electrical stimulation.Results – Immediately after SE, ΔFosB immunoreactivity was widespread in all the hippocampal regions, while no positive cell nuclei were found in NEC. In the following days, a general decrease in ΔFosB levels was observed in all the positive areas, reaching the lowest levels 7 days after. However, the subiculum presented a smoother decrease and ΔFosB levels were significantly higher than in the other areas. A sharp increase in ΔFosB immunoreactivity occurred in the dentate gyrus 14 days after SE, when positive cell nuclei reappeared also in other regions. Twenty-one days after SE, ΔFosB levels were increased in all the hippocampal regions apart CA3 and the medial entorhinal cortex. The histopathological analysis demonstrated a large damage in layer III of the medial entorhinal cortex, while CA was generally preserved. By counting pyramidal neurons in CA3, only a 10% decrease in cell number was found (p<0.05 vs NEC). Hence, we postulated that CA3 could be hypoactive in pilocarpine-treated spontaneously epileptic animals. This hypothesis was confirmed by analyzing the intensity of intrinsic optical signals detected in CA3 after maximal stimulation of the dentate gyrus. Again, by directly stimulating the CA3 pyramidal layer we were able to record IOSs as intense as in NEC, proving that this region is spared from damage.Conclusions - These findings indicate that in epileptic rats, and perhaps in MTLE patients, mechanisms other than neuronal loss hamper CA3 network synchronization and thus the ability of hippocampal output ability to control ictogenesis in the EC.
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|Anno di pubblicazione:||2004|
|Titolo:||Ipoattività dei neuroni piramidali dell’area CA3 in un modello animale di epilessia del lobo temporale.|
|Autori:||E. Baldelli; I. Zini; G. Biagini; G. D'Arcangelo; V. Tancredi; M. D'Antuono; M. Avoli|
|Appare nelle tipologie:||Articolo su rivista|
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