Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain

The excitatory amino acid glutamate has been implicated in the neurodegener ation associated with several different central nervous system diseases. Tr eatment with kainic acid (KA), a glutamate analog known to activate the AMP A/KA subtype of glutamate receptor, has been widely used as a model of epil epsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period fo llowing KA-induced status epilepticus in adult. female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Label ing with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was obse rved within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the pirifo rm cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain f ollowing KA treatment were also examined using the myelin-specific Black-Go ld (BG) stain, Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h su rvival time-point. Both stains showed a temporal progression of brain damag e throughout the affected areas. By 2 months post-treatment, few degenerati ng neurons could be detected and abnormal myelin was absent in most regions . As myelin chan,aes can be seen prior to neuronal degeneration, and oligod endrocytes express functional AMPA/kainate-type glutamate receptors, the ne urodegeneration and myelin pathologies may occur as independent events. Thu s, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing e xperiments. (C) 2000 Elsevier Science B.V. All rights reserved.