Hippocampal sclerosis: A review on current research status and its mechanisms

Hippocampal sclerosis (HS) is a pathological condition characterized by significant loss of hippocampal neurons and gliosis. This condition represents the most common neuropathological change observed in patients with temporal lobe epilepsy (TLE) and is also found in aging individuals. TLE related to HS is the most prevalent type of drug-resistant epilepsy in adults, and its underlying mechanisms are not yet fully understood. Therefore, developing improved methods for predicting and treating drug-resistant patients with TLE-HS is crucial. Patients with TLE-HS often experience cognitive impairment and psychological comorbidities, significantly affecting their quality of life. Consequently, a thorough review of the current research status of TLE-HS is essential, focusing on its prediction, diagnosis, treatment, and underlying mechanisms. The hippocampus plays a pivotal role in memory and cognition. HS of aging (HS-Aging), a condition linked to dementia in the ultra-elderly, is marked by severe CA1 (cornu ammonis) neuronal loss and frequent transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, often misdiagnosed as Alzheimer's disease (AD). Nonetheless, clinical characteristics and patterns of hippocampal atrophy can help differentiate between the two disorders. This review aims to provide a comprehensive overview of the pathological features of HS, the relevant mechanisms underlying TLE-HS and HS-Aging, current imaging diagnostic techniques, including machine learning, and available treatment modalities. It also explores the prognosis and comorbidities related to these conditions. Future research directions include establishing animal models to clarify the poorly understood mechanisms underlying HS, particularly those related to emotional processing. Investigating post-HS behavioral and cognitive changes in these models will lay the foundation for further advancements in this field. This review is a cornerstone for future investigations and suggests additional research endeavors.