Progression of spontaneous seizures after status epilepticus is associatedwith mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons

The development of spontaneous limbic seizures was investigated in a rat mo del in which electrical tetanic stimulation of the angular bundle was appli ed for up to 90 min. This stimulation produced behavioural and electrograph ic seizures that led to a status epilepticus (SE) in most rats (71%). Long- term EEG monitoring showed that the majority of the rats (67%) that underwe nt SE, displayed a progressive increase of seizure activity once the first seizure was recorded after a latent period of about 1 week. The other SE ra ts (33%) did not show this progression of seizure activity. We investigated whether these different patterns of evolution of spontaneous seizures coul d be related to differences in cellular or structural changes in the hippoc ampus. This was the case regarding the following changes. (i) Cell loss in the hilar region: in progressive SE rats this was extensive and bilateral w hereas in nonprogressive SE rats it was mainly unilateral. (ii) Parvalbumin and somatostatin-immunoreactive neurons: in the hilar region these were al most completely eliminated in progressive SE rats but were still largely pr esent unilaterally in nonprogressive SE rats. (iii) Mossy fibre sprouting: in progressive SE rats, extensive mossy fibre sprouting was prominent in th e inner molecular layer. In nonprogressive SE rats, mossy fibre sprouting w as also present but less prominent than in progressive SE rats. Although mo ssy fibre sprouting has been proposed to be a prerequisite for chronic seiz ure activity in experimental temporal lobe epilepsy, the extent of hilar ce ll death also appears to be an important factor that differentiates between whether or not seizure progression will occur.