Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy
Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy
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DOI：
10.1111/j.1528-1167.2006.00872.x
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发表时间：
2006-01-01
期刊：
影响因子：
5.6
通讯作者：
Fornai, Francesco
中科院分区：
文献类型：
--
作者：
Giorgi, Filippo S.;Mauceli, Giuseppe;Fornai, Francesco
目的：大鼠前梨状皮质（APC）微量注入双丘蓝碱引起的散发性癫痫发作在去肾上腺素能核蓝斑（LC）损伤后转化为边缘癫痫持续状态（SE）。本研究的目的是评价这种新型SE对继发性癫痫发生的慢性影响。我们进一步将去甲肾上腺素（NE）的丧失与海马苔藓纤维发芽联系起来。方法：雄性Sprague Dawley大鼠以全身生理盐水或DSP-4（一种源自LC的去甲肾上腺素能末梢的神经毒素）处理，3 d后向APC微注双球茎碱，45 d后处死。未处理大鼠和经DSP-4预处理的假手术大鼠分别作为对照。进行以下评估：(a)监测急性发作和延迟发生的自发性复发性发作（SRS）；(b)海马、额叶和嗅皮质内NE水平；(c)海马背侧齿状回内分子层出现苔状纤维萌芽。结果：30%的去甲肾上腺素能末梢缺失大鼠，APC诱发SE后再进行SRS。相反，在完整大鼠中引起的癫痫发作不会导致慢性癫痫发生。与基线水平相比，未治疗大鼠和预处理过dsp -4的大鼠的癫痫发作/SE并未改变NE水平。spd -4 +双球茎碱诱导SE大鼠发生SRS，并伴有海马苔藓纤维萌发。结论：去甲肾上腺素能丧失可将局部引起的零星癫痫发作转化为癫痫性SE，并伴有齿状回内苔藓纤维的萌发。
Purpose: A lesion of the noradrenergic nucleus Locus Coeruleus (LC) converts sporadic seizures evoked by microinfusion of bicuculline into the anterior piriform cortex (APC) of rats into limbic status epilepticus (SE). The purpose of this study was to evaluate the chronic effects of this new model of SE on the onset of secondary epileptogenesis. We further related the loss of noradrenaline (NE) with hippocampal mossy fiber sprouting.Methods: Male Sprague Dawley rats were treated with systemic saline or DSP-4 (a neurotoxin selective for noradrenergic terminals originating from the LC), microinfused with bicuculline into the APC three days later, and sacrificed after 45 days. Naive and DSP-4 pretreated sham-operated rats served as respective controls. The following evaluations were performed: (a) monitoring of acute seizures and delayed occurrence of spontaneous recurrent seizures (SRS); (b) NE levels in the hippocampus, frontal and olfactory cortex; (c) occurrence of mossy fiber sprouting into the inner molecular layer of the dentate gyrus of the dorsal hippocampus.Results: In 30% of rats lacking noradrenergic terminals, SE evoked from the APC was followed by SRS. Conversely, seizures evoked in intact rats did not result in chronic epileptogenesis. Seizures/SE did not modify NE levels as compared with baseline levels both in naive and DSP-4-pretreated rats. Rats undergoing SE following DSP-4 + bicuculline developed SRS which were accompanied by hippocampal mossy fiber sprouting.Conclusions: Noradrenergic loss converts focally induced sporadic seizures into an epileptogenic SE, which is accompanied by mossy fiber sprouting within the dentate gyrus.