Mazarati A M, Liu H, Soomets U, Sankar R, Shin D, Katsumori H, Langel U, Wasterlain C G
Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA.
J Neurosci. 1998 Dec 1;18(23):10070-7. doi: 10.1523/JNEUROSCI.18-23-10070.1998.
We examined the role of hippocampal galanin in an animal model of status epilepticus (SE). Control rats showed abundant galanin-immunoreactive (Gal-IR) fibers in the dentate hilus, whereas no Gal-IR neurons were observed. Three hours after the onset of self-sustaining SE (SSSE), induced either by intermittent stimulation of the perforant path for 30 min (PPS) or by injection of lithium and pilocarpine, Gal-IR fibers disappeared in the hilus and remained absent for up to 1 week afterward. Twelve hours after the induction of SE by PPS or 3 hr after pilocarpine administration, Gal-IR neurons appeared in the hilus; these neurons increased in number after 1 d and gradually declined 3 and 7 d later. Galanin concentration in the hippocampus, measured by ELISA, significantly decreased on the plateau of SSSE and increased 24 hr after PPS. Galanin (0.05 nmol) injected into the hilus prevented the induction of SSSE, and 0.5 nmol of galanin stopped established SSSE. These effects were attenuated by galanin receptor antagonists (M35 > M40 >/= M15). 2-Ala-galanin (5 nmol), a putative agonist of galanin type 2 receptors, prevented but was unable to stop SSSE. M35 facilitated the development of SSSE when given before PPS. We suggest that hippocampal galanin acts as an endogenous anticonvulsant via galanin receptors. SE-induced galanin depletion in the hippocampus may contribute to the maintenance of seizure activity, whereas the increase of galanin concentration and the appearance of galanin-immunoreactive neurons may favor the cessation of SSSE. The seizure-protecting action of galanin SSSE opens new perspectives in the treatment of SE.
我们在癫痫持续状态（SE）动物模型中研究了海马甘丙肽的作用。对照大鼠在齿状回门区显示出丰富的甘丙肽免疫反应性（Gal-IR）纤维，但未观察到Gal-IR神经元。在通过对穿通通路进行30分钟的间歇性刺激（PPS）或注射锂和匹鲁卡品诱导出现自主持续性SE（SSSE）3小时后，门区的Gal-IR纤维消失，并且在随后长达1周的时间内一直未出现。在通过PPS诱导SE 12小时后或在给予匹鲁卡品3小时后，门区出现了Gal-IR神经元；这些神经元在1天后数量增加，并在3天和7天后逐渐减少。通过酶联免疫吸附测定法（ELISA）测量，海马中的甘丙肽浓度在SSSE平台期显著降低，并在PPS后24小时升高。向门区注射甘丙肽（0.05 nmol）可预防SSSE的诱导，而0.5 nmol的甘丙肽可终止已确立的SSSE。这些作用被甘丙肽受体拮抗剂减弱（M35 > M40 >= M15）。2-丙氨酸-甘丙肽（5 nmol），一种假定的甘丙肽2型受体激动剂，可预防但无法终止SSSE。在PPS之前给予M35会促进SSSE的发展。我们认为海马甘丙肽通过甘丙肽受体发挥内源性抗惊厥作用。SE诱导的海马甘丙肽耗竭可能有助于癫痫活动的维持，而甘丙肽浓度的增加和甘丙肽免疫反应性神经元的出现可能有利于SSSE的终止。甘丙肽对SSSE的抗癫痫作用为SE的治疗开辟了新的前景。
