Bengzon J, Kokaia Z, Lindvall O
Department of Neurology, University Hospital, Lund, Sweden.
Exp Neurol. 1993 Jul;122(1):143-54. doi: 10.1006/exnr.1993.1115.
Grafts of fetal noradrenaline (NA)-rich locus coeruleus (LC) tissue implanted bilaterally into the hippocampus in 6-hydroxydopamine (6-OHDA) treated, hyperexcitable rats retard seizure development in hippocampal kindling. We report that bilateral intrahippocampal LC grafts failed to affect the severity of seizures when implanted in 6-OHDA-treated, already kindled rats. Furthermore, a noradrenergic hyperinnervation of the hippocampus, produced by grafting fetal LC tissue into the intact brain, did not influence hippocampal kindling development. Kindling leads to long-term reduction in basal hippocampal NA release from the intrinsic locus coeruleus system as monitored using intracerebral microdialysis. This deficit could be reversed by intrahippocampal LC grafts implanted into previously kindled rats. However, these unilateral grafts had no effect on the severity of the kindled convulsions despite a noradrenergic hyperinnervation of the hippocampus around the grafts. In conclusion, these data show a distinct functional specificity of intrahippocampal LC grafts in the kindling model of epilepsy. Similar to the intrinsic noradrenergic system, the grafted neurons have a major inhibitory influence on seizure development but are ineffective against established convulsions.
将富含去甲肾上腺素（NA）的胎儿蓝斑（LC）组织双侧植入经6-羟基多巴胺（6-OHDA）处理的、兴奋性过高的大鼠海马体中，可延缓海马体点燃模型中的癫痫发作发展。我们报告称，当将双侧海马内LC移植片植入经6-OHDA处理且已被点燃的大鼠体内时，未能影响癫痫发作的严重程度。此外，将胎儿LC组织移植到完整大脑中所产生的海马体去甲肾上腺素能超神经支配，并未影响海马体点燃的发展。如使用脑内微透析监测所示，点燃会导致来自固有蓝斑系统的基础海马体NA释放长期减少。将海马内LC移植片植入先前已被点燃的大鼠体内可逆转这种缺陷。然而，尽管移植片周围的海马体存在去甲肾上腺素能超神经支配，但这些单侧移植片对点燃惊厥的严重程度并无影响。总之，这些数据显示了海马内LC移植片在癫痫点燃模型中的独特功能特异性。与固有去甲肾上腺素能系统类似，移植的神经元对癫痫发作发展具有主要抑制作用，但对已确立的惊厥无效。
