Jacobs K M, Graber K D, Kharazia V N, Parada I, Prince D A
Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305, USA.
Epilepsia. 2000;41 Suppl 6:S153-61. doi: 10.1111/j.1528-1157.2000.tb01574.x.
Lesions that occur either during fetal development or after postnatal brain trauma often result in seizures that are difficult to treat. We used two animal models to examine epileptogenic mechanisms associated with lesions that occur either during cortical development or in young adults. Results from these experiments suggest that there are three general ways that injury may induce hyperexcitability. Direct injury to cortical pyramidal neurons causes changes in membrane ion channels that make these cells more responsive to excitatory inputs, including increases in input resistance and a reduction in calcium-activated potassium conductances that regulate the rate of action potential discharge. The connectivity of cortical circuits is also altered after injury, as shown by axonal sprouting within pyramidal cell intracortical arbors. Enhanced excitatory connections may increase recurrent excitatory loops within the epileptogenic zone. Hyperinnervation attributable to reorganization of thalamocortical, callosal, and intracortical circuitry, and failure to prune immature connections, may be prominent when lesions affect the developing neocortex. Finally, focal injury can produce widespread changes in gamma-aminobutyric acid and glutamate receptors, particularly in the developing brain. All of these factors may contribute to epileptogenesis.
在胎儿发育期间或出生后脑外伤后出现的损伤，常常会导致难以治疗的癫痫发作。我们使用两种动物模型来研究与皮质发育期间或年轻成年期出现的损伤相关的致痫机制。这些实验的结果表明，损伤可能通过三种一般方式诱发过度兴奋。对皮质锥体细胞的直接损伤会导致膜离子通道发生变化，使这些细胞对兴奋性输入更敏感，包括输入电阻增加以及调节动作电位发放速率的钙激活钾电导降低。损伤后皮质回路的连接性也会改变，如锥体细胞皮质内树突分支内的轴突发芽所示。增强的兴奋性连接可能会增加致痫区内的反复兴奋性回路。当损伤影响发育中的新皮质时，丘脑皮质、胼胝体和皮质内回路重组导致的过度神经支配以及未能修剪未成熟连接可能会很突出。最后，局灶性损伤可在γ-氨基丁酸和谷氨酸受体中产生广泛变化，尤其是在发育中的大脑中。所有这些因素都可能促成癫痫发生。
