Evidence Against a Pathogenic Role For Mossy Fiber Sprouting.

Abstract

Is mossy fiber sprouting present at the time of the first spontaneous seizures in rat experimental temporal lobe epilepsy? Nissinen J, Lukasiuk K, Pitkanen A Hippocampus 2001;11:299–310 Purpose The contribution of mossy fiber sprouting to the generation of spontaneous seizures in the epileptic brain is under dispute. This study addressed this question by examining whether sprouting of mossy fibers is present at the time of appearance of the first spontaneous seizures in rats, and whether all animals with increased sprouting have spontaneous seizures. Methods Epileptogenesis was induced in 16 rats by electrically stimulating the lateral nucleus of the amygdala for 20–30 min until the rats developed self-sustained status epilepticus (SSSE). During and after SSSE, rats were monitored in the long term with continuous video-EEG until they developed a second spontaneous seizure (8–54 days). Thereafter, monitoring was continued for 11 days to follow up seizure frequency. The density of mossy fiber sprouting was analyzed from Timm-stained preparations. The density of hilar neurons was assessed from thionine-stained sections. Results Of 16 rats, epilepsy developed in 14. In epileptic rats, the density of mossy fiber sprouting did not correlate with the severity or duration (115–620 min) of SSSE, delay from SSSE to occurrence of first (8–51 days) or second (8–54 days) spontaneous seizure, or time from SSSE to perfusion (20–63 days). In the temporal end of the hippocampus, the sprouting correlated with the severity of neuronal damage (ipsilateral: r = −0.852, p < 0.01; contralateral: r = −0.748, p < 0.01). The two animals without spontaneous seizures also had sprouting. Increased density of sprouting in animals without seizures and its association with the severity of neuronal loss was confirmed in another series of 30 stimulated rats that were followed up with video-EEG monitoring for 60 days. Conclusions Our data indicate that although mossy fiber sprouting is present in all animals with spontaneous seizures, its presence is not necessarily associated with the occurrence of spontaneous seizures.