Neuronal loss or replacement in the injured adult cerebral neocortex induces extensive remodeling of intrinsic and afferent neural systems.
The question of how the cerebral cortex responds over time to changes in cortical neuronal number was addressed by inducing excitotoxic cortical neuronal loss, either alone or followed by homotypic fetal cortical cell suspension grafts, in adult rats. Following neuronal cell loss, rapid gliosis and inflammation temporarily maintained tissue volume. As gliosis subsided, tissue shrinkage occurred until the ratio of glia to neurons approached that of normal neocortex. After neuronal loss, total cortical glutamate uptake and glutamic acid decarboxylase activity dropped markedly and remained low, and there was a gradual but considerable reduction in the total size of afferent fiber networks. However, when expressed as concentrations per unit of tissue or protein, histological and neurochemical cortical markers showed increases during the phase of tissue shrinkage and in the long-term equilibrated to near normal levels. Retrograde tracing studies showed that the reduction in total afferent fiber network is accompanied by the atrophy of afferent neuronal cell bodies. Grafts of fetal cortical cells placed after excitotoxic lesions provided long-term reconstitution of cortical tissue mass, maintained afferent fiber systems, and prevented both the atrophy and surrounding cellular gliosis of some afferent neuronal cell bodies for over a year, but were unable to innervate the main cortical target regions in the host. Thus after neuronal loss or replacement, the adult cerebral neocortex and its afferent systems remodel to a density of neurons, glia, and afferent fibers similar to that found in intact tissue, illustrating structural plasticity toward a dynamic equilibrium.
Isacson
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Department of Neurology, Harvard Medical School, McLean Hospital, Belmont, MA 02178.
Sofroniew
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MV
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001370:Axonal Transport; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007608:Kainic Acid / Q000633:toxicity*; D016202:N-Methylaspartate / Q000633:toxicity*; D009410:Nerve Degeneration; D009416:Nerve Regeneration; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013562:Sympathectomy
D005971:Glutamates; D009498:Neurotoxins; D012701:Serotonin; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid; D009638:Norepinephrine