Altered corticogenesis and neuronal morphology in irradiation-induced cortical dysplasia: a Golgi-Cox study
Miguel Marín-Padilla1, Regina J Tsai, Michael A King
1Department Neuroscience Research, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
Cortical dysplasia has a strong clinical association with epilepsy and mental retardation, but the relationship between alterations in cortical structure and function in dysplasia-related disorders is poorly understood. The cerebral cortex of irradiated rats, an experimental model of cortical dysplasia, was studied using cresyl violet-stained sections and the Golgi-Cox method. The irradiated cortex is characterized by reductions in size, volume, and number of neurons and fibers reflecting the original lethal injury to neuronal precursors. Consequently, only neurons that survived this injury were able to continue their, albeit altered, development. The result is an altered corticogenesis characterized by neuronal, fiber circuitry, and microvascular alterations. Abnormal aggregates (nodules) of excitatory pyramidal neurons with altered dendritic profiles and functional territories are found between 200 and 400 microm from the pial surface. Their horizontal dendritic profiles and functional territories contrast with the vertical (columnar) dendritic profiles and functional territories of normal pyramidal neurons. This horizontal concentration of spiny dendrites and, hence, of excitatory synaptic contacts suggests a response to the presence of an abnormal horizontal plexus of afferent fibers terminals. Stellate neurons, some morphologically compatible with inhibitory basket cells, are also essential components of these nodules. Some neuronal nodules are characterized by a rich plexus of anastomotic capillaries that contrasts with the sparser vasculature of surrounding gray matter tissue. The presence of well-vascularized aggregates of altered pyramidal and inhibitory neurons suggests a high level of metabolic activity. Well-vascularized deep heterotopias are also found. We propose that the functional activity of well-vascularized neuronal nodules and heterotopias could play a role in the abnormal cortical function in this model.
