Characterization of Neuronal Migration Disorders in Neocortical Structures: Loss or Preservation of Inhibitory Interneurons?
Article first published online: 2 AUG 2005
Volume 41, Issue 7, pages 781–787, July 2000
How to Cite
Schwarz, P., Stichel, C. C. and Luhmann, H. J. (2000), Characterization of Neuronal Migration Disorders in Neocortical Structures: Loss or Preservation of Inhibitory Interneurons?. Epilepsia, 41: 781–787. doi: 10.1111/j.1528-1157.2000.tb00243.x
- Issue published online: 2 AUG 2005
- Article first published online: 2 AUG 2005
- Accepted February 4, 2000
- Cell counts;
- Neuronal migration disorder;
Summary: Purpose: Neuronal migration disorders (NMD) are often associated with therapy-resistant epilepsy. In human cerebral cortex, this hyperexcitability has been correlated with a loss of inhibitory interneurons. We used a rat model of focal cortical NMD (microgyria) to determine whether the expression of epileptiform activity in this model coincides with a decrease in inhibitory interneurons.
Methods: In 2- to 4-month-old rats, the density of interneurons immunoreactive for γ-aminobutyric acid (GABA), cal-bindin, and parvalbumin was determined in fronto-parietal cortex in nine 200-μm-wide sectors located up to 2.5 mm lateral and 2.0 mm medial from the lesion center in primary parietal cortex (Par 1). Quantitative measurements in homotopic areas of age-matched sham-operated rats served as controls.
Results: The freeze lesion performed in newborn rat cortex resulted in adult rats with a microgyrus extending in a rostro-caudal direction from frontal to occipital cortex. The density of GABA- and parvalbumin-positive neurons in fronto-parietal cortex was not significantly different between lesioned and control animals. Only the density of calbindin-immunoreactive neurons located 1.0 mm lateral and 0.5 mm medial from the lesion was significantly (Student t test, p > 0.05) larger in freeze-lesioned rats (5.817 ± 562 and 6,400 ± 795 cells per mm3, respectively; n = 12) compared with measurements in homotopic regions in Parl cortex of controls (4,507 ± 281 and 4,061 ± 319 cells per mm3, respectively; n = 5).
Conclusions: The previously reported widespread functional changes in this model of cortical NMD are not related to a general loss of inhibitory interneurons. Other factors, such as a decrease in GABA receptor density, modifications in GABAA receptor subunit composition, or alterations in the excitatory network, e.g., an increase in the density of calbindin-immunoreactive pyramidal cells, more likely contribute to the global disinhibition and widespread expression of pathophysiological activity in this model of cortical NMD.