Seizure development and noradrenaline release in kindling epilepsy after noradrenergic reinnervation of the subcortically deafferented hippocampus by superior cervical ganglion or fetal locus coeruleus grafts.
Solid pieces of fetal locus coeruleus (LC) or superior cervical ganglion (SCG) were placed into a fimbria-fornix lesion cavity in 6-hydroxydopamine-treated, noradrenaline (NA)-denervated rats. Six to 8 months later, all animals were subjected to electrical kindling stimulations in the hippocampus until they had reached the fully kindled state. Nongrafted lesioned animals showed markedly increased kindling rate which was partly attenuated by LC but not SCG grafts. In both LC- and SCG-grafted animals, dopamine beta-hydroxylase immunocytochemistry demonstrated a high density of graft-derived noradrenergic fibers in the dorsal hippocampus, whereas reinnervation of the ventral hippocampus was much more sparse. Subregional distribution of these fibers within the hippocampus was different in the two grafted groups. Both grafts partly restored basal extracellular NA levels in the hippocampus and reacted to generalized seizures by a significant (two- to threefold) increase of NA release, as measured by intracerebral microdialysis. Our data indicate (i) that seizure activity can regulate transmitter release from noradrenergic neurons in both LC and SCG grafts, (ii) that only fetal LC grafts retard seizure development in kindling, and (iii) that the inability of SCG implants to influence kindling epileptogenesis could be due to a lack of synaptic contacts between the graft-derived ganglionic fibers and host hippocampal neurons.
Kokaia
M
M
Department of Neurology, University Hospital, Lund, Sweden.
Cenci
M A
MA
Elmér
E
E
Nilsson
O G
OG
Kokaia
Z
Z
Bengzon
J
J
Björklund
A
A
Lindvall
O
O
D000818:Animals; D003714:Denervation; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D005728:Ganglia, Sympathetic / Q000637:transplantation; D006624:Hippocampus / Q000503:physiopathology*; D007150:Immunohistochemistry; D007696:Kindling, Neurologic; D008125:Locus Coeruleus / Q000637:transplantation; D008297:Male; D017551:Microdialysis; D009416:Nerve Regeneration; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology*
D009638:Norepinephrine