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GENERAL INTRODUCTION & OUTLINE OF THE THESIS
  Figure 3. Schematic overview of layer marker expression in normal cortex, TSC cortical tubers and FCD type IIb. A Cortical layer markers are expressed in normal cortex as follows: Cux2: layers II and III (blue); Satb2: layers II, III, IV, and V (green); RORβ in layer IV and to a lesser extent layer VI (orange); ER81 in layers V and VI (purple), and Tbr1 in layers V and VI and few white mat- ter neurons (red). B and C Expression pattern of cortical layer markers in tubers and FCD type IIb: dysmorphic neurons strongly expressed Cux2, RORβ, and ER81 and to a lesser extent Satb2 throughout all layers of the cortex. They did not express Tbr1. Giant cells of cortical tubers often expressed Satb2, ER81, or none of the markers. Balloon cells of FCD type IIb showed a similar pattern although to a lesser extent, BCs did more frequently express none of the markers. Trends observed in normal-appearing neurons: Cux2+ and Satb2+ neurons were less in cortical tubers. The RORβ+ cells of layer IV were reduced in both pathologies. The expression of Tbr1 and ER81 was increased in the upper cortical layers and was also present in normal-appearing neurons of the white matter. Triangles: neurons; circles: giant/balloon cells; SG: supragranular layers; IG: infra- granular layers. Adapted from Mühlebner et al., J Neurodev Disorder, 2016;8:9 57.
a consequence of a deregulation of the mTOR signaling 39, 72, 84-89. The introduction in the last decade of techniques for next generation genomic analysis has resulted in the identification of novel genetic causes of MCDs, showing that a large spectrum of mal- formations is associated with abnormal cell proliferation and abnormal neuronal/glial morphology caused by mutations affecting the mTOR pathway 88-92.
Inflammation and epileptogenesis
A dysregulated inflammatory response is present in various pathologies of the CNS, and increasing evidence shows an important role of brain inflammation in the pathophys- iology of epilepsy 93-96. The first indications about the crucial role of inflammation in human epilepsy were derived from clinical observations that anti-inflammatory phar- macological treatment could decrease seizures in some drug-resistant epilepsies 94, 97. Additionally, febrile seizures, which are seizures that are induced by fever in infants and
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