Effects of Prolonged Seizures on Basal Forebrain Cholinergic Neurons: Evidence and Potential Clinical Relevance

Seizures originating from limbic structures, especially when prolonged for several minutes/hours up to status epilepticus (SE), can cause specific neurodegenerative phenomena in limbic and subcortical structures. The cholinergic nuclei belonging to the basal forebrain (BF) (namely, medial septal nucleus (MSN), diagonal band of Broca (DBB), and nucleus basalis of Meynert (NBM)) belong to the limbic system, while playing a pivotal role in cognition and sleep-waking cycle. Given the strong interconnections linking these limbic nuclei with limbic cortical structures, a persistent effect of SE originating from limbic structures on cBF morphology is plausible. Nonetheless, only a few experimental studies have addressed this issue. In this review, we describe available data and discuss their significance in the scenario of seizure-induced brain damage. In detail, the manuscript moves from a recent study in a model of focally induced limbic SE, in which the pure effects of seizure spreading through the natural anatomical pathways towards the cholinergic nuclei of BF were tracked by neuronal degeneration. In this experimental setting, a loss of cholinergic neurons was measured in all BF nuclei, to various extents depending on the specific nucleus. These findings are discussed in the light of the effects on the very same nuclei following SE induced by systemic injections of kainate or pilocarpine. The various effects including discrepancies among different studies are discussed. Potential implications for human diseases are included.