Cavalheiro E A, Silva D F, Turski W A, Calderazzo-Filho L S, Bortolotto Z A, Turski L
Departamento de Neurologia e Neurocirurgia, Escola Paulista de Medicina, Sao Paulo, Brazil.
Brain Res. 1987 Dec 15;465(1-2):43-58. doi: 10.1016/0165-3806(87)90227-6.
Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydrochloride were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral patterns in developing rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoclonic movements of the limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense behavioral signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12-day-old-rats. The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocampus and cortex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings during the second week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pilocarpine, 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered in 15-21-day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to motor limbic seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased susceptibility to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs, and an increased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced convulsions high voltage fast activity superposed over hippocampal theta-rhythm, progressed into high voltage spiking and spread to cortical records. The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morphological analysis of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage or an attenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological breakdown was seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in the substantia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was present in 4-5-week-old rats.(ABSTRACT TRUNCATED AT 400 WORDS)
在3至90日龄的大鼠中研究了全身注射盐酸毛果芸香碱所引起的行为、脑电图及形态学变化。100、200和380mg/kg的毛果芸香碱在发育中的大鼠身上呈现出一系列特征性的行为模式。多动或活动减少、震颤、姿势控制丧失、抓挠、点头及肢体肌阵挛运动在3至9日龄大鼠的行为中占主导。该年龄组未观察到明显的运动性癫痫发作。当给12日龄大鼠注射毛果芸香碱时，一些动物出现更强烈的行为体征，进而发展为边缘性癫痫发作和癫痫持续状态。这些动物的脑电图活动从出生后第一周海马体和皮质同时记录到的低电压棘波，发展为海马体局部癫痫活动，并在出生后第二周扩散到皮质记录中。给3至12日龄大鼠注射100 - 380mg/kg毛果芸香碱后，其大脑未检测到形态学改变。15至21日龄大鼠出现了毛果芸香碱注射后成人型的行为和脑电图后遗症。给15至21日龄大鼠注射100 - 380mg/kg毛果芸香碱后，运动不能、震颤和点头发展为运动性边缘性癫痫发作和癫痫持续状态。毛果芸香碱的致死毒性在出生后第三周达到50%。相对于年长和年幼大鼠，对毛果芸香碱惊厥作用的易感性增加表现为行为和脑电图体征的潜伏期缩短，癫痫发作严重程度增加。在经历毛果芸香碱诱导惊厥的15至21日龄大鼠中，海马体θ节律上叠加的高电压快速活动发展为高电压棘波并扩散到皮质记录中。脑电图活动变得高度同步，然后发展为癫痫发作和癫痫持续状态。对15至21日龄大鼠额叶前脑切片进行形态学分析，这些大鼠在毛果芸香碱作用后发生癫痫持续状态，结果显示无损伤或损伤模式减弱。在出现癫痫相关脑损伤的15至21日龄大鼠中，海马体、杏仁核、嗅觉皮质、新皮质和某些丘脑核出现形态学破坏。黑质和外侧丘脑核未检测到损伤。4至5周龄大鼠出现了在范围和部位上均为成人型的脑损伤。（摘要截取自400字）
