Neural mechanisms and potential treatment of epilepsy and its complications

Abstract

The factors underlying epilepsy are multifaceted, but recent research suggests that the brain's neural circuits, which play a key role in controlling the balance between epileptic and antiepileptic factors, may lie at the heart of epilepsy. This article provides a comprehensive review of the neural mechanisms and potential treatment of intractable epilepsy from neural inflammatory responses, melanocortin circuits in brain and pedunculopontine tegmental nucleus. Further studies should be undertaken to elucidate the nature of neural circuits so that we may more effectively apply these new preventive and symptomatic therapies to the patient suffering from medically refractory seizures and its complications.

Keywords: Intractable epilepsy; melanocortin circuits; neural inflammatory responses; pedunculopontine tegmental nucleus.

Figure 1

Summary diagram of the neural bases involving in visual, auditory and gastrointestinal complaints in patients with intractable epilepsy. A. Sagittal view of the mouse brain. PRV-614 spreads from infected retinal ganglion cells through the optic nerve to second-order neurons in the supracharismatic nucleus, dorsal and ventral aspects of the geniculate nuclei [dorsal aspect of the lateral geniculate nucleus (LGN) and ventral aspect of the lateral geniculate nucleus], intergeniculate nucleus, and pPPTg. Transport of PRV-614 is restricted to retrograde-only pathways. Although cells of the retinal ganglia are infected with PRV-614, this virus is restricted from anterograde spread through the optic nerve to retinorecipient neurons. Instead, retrograde spread of infection to first-order neurons in the ciliary ganglion leads to transport through the oculomotor nerve to second-order neurons in the Edinger-Westphal nucleus (EW) and pPPTg. Figure adapted from QX Hong (Epilepsy Behav, 2014); B. It is showing that the central circuits from the subthalamic nucleus to the stomach wall. PRV-614 injected into the ventral stomach wall is taken up by vagal terminals and enteric neurons, and then is retrogradely transported to the dorsal motor nucleus of the vagus (DMV), the nucleus of the solitary tract (NST) the area postrema (AP). Further replication and retrograde transsynaptic transport to regions of interest, including STN and most of the CNS including the STN, pedunculopontine tegmental nucleus (PPTg), paraventricular nuclei of the hypothalamus (PVN), and cortex thalamus. DVC, the dorsal vagal complex; STN, subthalamic nucleus. Figure adapted from HB Xiang (Brain, 2013; Parkinsonism Relat Disord, 2014). C. An overview of the binaural pathway from the outer ear to the auditory cortex via the eighth cranial nerve (the auditory nerve). The central auditory system receives the neural coding from the organ of Corti via the eighth cranial nerve (the auditory nerve). PRV-614 was injected into the ear canal in MC4R-GFP transgenic mouse, and the distribution patterns of PRV-614-positive neuronal labeling were analyzed in the auditory cortex, inferior colliculus, caudal PPTg (cPPTg), and olivary complex. PRV-614/MC4R-GFP dual labeled neurons were detected in the auditory cortex, inferior colliculus and cPPTg, suggesting direct melanocortinergic neuronal circuit from ear canal to the cPPTg. In contrast to the cPPTg, we didn’t detect PRV-614/MC4R-GFP neurons in the rostral PPTg (rPPTg).