Postlesional epilepsy: The ultimate brain plasticity

Lesions that occur either during fetal development or after postnatal brain trauma often result in seizures that are difficult to treat. We used two a nimal models to examine epileptogenic mechanisms associated with lesions th at occur either during cortical development or in young adults. Results fro m these experiments suggest that there are three general ways that injury m ay induce hyperexcitability. Direct injury to cortical pyramidal neurons ca uses changes in membrane ion channels that make these cells more responsive to excitatory inputs, including increases in input resistance and a reduct ion in calcium-activated potassium conductances that regulate the rate of a ction potential discharge. The connectivity of cortical circuits is also al tered after injury, as shown by axonal sprouting within pyramidal cell intr acortical arbors. Enhanced excitatory connections may increase recurrent ex citatory loops within the epileptogenic zone. Hyperinnervation attributable to reorganization of thalamocortical, callosal, and intracortical circuitr y, and failure to prune immature connections, may be prominent when lesions affect the developing neocortex. Finally. focal injury can produce widespr ead changes in gamma-aminobutyric acid and glutamate receptors, particularl y in the developing brain. All of these factors may contribute to epileptog enesis.