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The Journal of Neuroscience, December 1, 2000, 20(23):8788-8801

Fetal Hippocampal Grafts Containing CA3 Cells Restore Host Hippocampal Glutamate Decarboxylase-Positive Interneuron Numbers in a Rat Model of Temporal Lobe Epilepsy

Ashok K. Shetty and Dennis A. Turner

Departments of Surgery (Neurosurgery) and Neurobiology, Duke University Medical Center. Durham, North Carolina 27710, and Medical Research and Surgery (Neurosurgery) Services, Veterans Affairs Medical Center, Durham, North Carolina 27705

Degeneration of CA3-pyramidal neurons in hippocampus after intracerebroventricular kainic acid (KA) administration, a model of temporal lobe epilepsy, results in hyperexcitability within both dentate gyrus and the CA1 subfield. It also leads to persistent reductions in hippocampal glutamate decarboxylase (GAD) interneuron numbers without diminution in Nissl-stained interneuron numbers, indicating loss of GAD expression in a majority of interneurons. We hypothesize that enduring loss of GAD expression in hippocampal interneurons after intracerebroventricular KA is attributable to degeneration of their CA3 afferent input; therefore, fetal CA3 grafts can restore GAD interneuron numbers through graft axon reinnervation of the host. We analyzed GAD interneuron density in the adult rat hippocampus at 6 months after KA administration after grafting of fetal mixed hippocampal, CA3 or CA1 cells into the CA3 region at 45 d after lesion, in comparison with "lesion-only" and intact hippocampus. In dentate and CA1 regions of the lesioned hippocampus receiving grafts of either mixed hippocampal or CA3 cells, GAD interneuron density was both significantly greater than lesion-only hippocampus and comparable with the intact hippocampus. In the CA3 region, GAD interneuron density was significantly greater than lesion-only hippocampus but less than the intact hippocampus. Collectively, the overall GAD interneuron density in the lesioned hippocampus receiving either mixed hippocampal or CA3 grafts was restored to that in the intact hippocampus. In contrast, GADinterneuron density in the lesioned hippocampus receiving CA1 grafts remained comparable with lesion-only hippocampus. Thus, grafts containing CA3 cells restore CA3 lesion-induced depletions in hippocampal GAD interneurons, likely by reinnervation of GAD-deficient interneurons. This specific graft-mediated effect is beneficial because reactivation of interneurons could ameliorate both loss of functional inhibition and hyperexcitability in CA3-lesioned hippocampus.

Key words: brain injury; GAD-67; hippocampus; neural grafting; nonpyramidal neurons; temporal lobe epilepsy

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20238788-14$05.00/0

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				A. K. Shetty, V. Zaman, and B. Hattiangady Repair of the Injured Adult Hippocampus through Graft-Mediated Modulation of the Plasticity of the Dentate Gyrus in a Rat Model of Temporal Lobe Epilepsy J. Neurosci., September 14, 2005; 25(37): 8391 - 8401. [Abstract] [Full Text] [PDF]

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