Biagini Giuseppe, Baldelli Enrica, Longo Daniela, Contri Miranda Baccarani, Guerrini Uliano, Sironi Luigi, Gelosa Paolo, Zini Isabella, Ragsdale David S, Avoli Massimo
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy.
J Neuropathol Exp Neurol. 2008 Jul;67(7):687-701. doi: 10.1097/NEN.0b013e318181b8ae.
In limbic seizures, neuronal excitation is conveyed from the entorhinal cortex directly to CA1 and subicular regions. This phenomenon is associated with a reduced ability of CA3 to respond to entorhinal cortex inputs. Here, we describe a lesion that destroys the perforant path in CA3 after status epilepticus (SE) induced by pilocarpine injection in 8-week-old rats. Using magnetic resonance imaging, immunohistochemical, and ultrastructural analyses, we determined that this lesion develops after 30 minutes of SE and is characterized by microhemorrhages and ischemia. After a longer period of SE, the lesion invariably involves the upper blade of the dentate gyrus. Adult rats treated with subcutaneous diazepam (20 mg kg for 3 days) did not develop the dentate gyrus lesion and had less frequent spontaneous recurrent seizures (p < 0.01). Young (3-week-old) rats rarely (20%) developed the CA3 lesion, and their spontaneous seizures were delayed (p < 0.01). To investigate the role of the damaged CA3 in seizure activity, we reinduced SE in adult and young epileptic rats. Using FosB/DeltaFosB markers, we found induction of FosB/DeltaFosB immunopositivity in CA3 neurons of young but not in adult rats. These experiments indicate that SE can produce a focal lesion in the perforant path that may affect the roles of the hippocampus in epileptic rats.
在边缘系统癫痫发作中，神经元兴奋从内嗅皮质直接传导至CA1和海马下托区域。这种现象与CA3对内嗅皮质输入作出反应的能力降低有关。在此，我们描述了一种在8周龄大鼠中通过毛果芸香碱注射诱导癫痫持续状态（SE）后破坏CA3区穿通通路的损伤。通过磁共振成像、免疫组织化学和超微结构分析，我们确定这种损伤在SE发作30分钟后出现，其特征为微出血和局部缺血。在较长时间的SE发作后，该损伤总是累及齿状回的上叶片。皮下注射地西泮（20mg/kg，连续3天）治疗的成年大鼠未出现齿状回损伤，且自发性反复癫痫发作频率较低（p<0.01）。年幼（3周龄）大鼠很少（20%）出现CA3区损伤，且其自发性癫痫发作出现延迟（p<0.01）。为了研究受损的CA3在癫痫活动中的作用，我们在成年和年幼癫痫大鼠中再次诱导SE发作。使用FosB/DeltaFosB标记物，我们发现年幼大鼠的CA3神经元中有FosB/DeltaFosB免疫阳性的诱导，而成年大鼠中则没有。这些实验表明，SE可在穿通通路中产生局灶性损伤，这可能会影响癫痫大鼠中海马的作用。
