Authors :
Presenting Author: tianfu li, MD, PhD – Sanbo Brain Hospital
Detlev Boison, Neurology – Rutgers University; Fan Chen, Neurology – Sanbo Brain Hospital; Yuguang Guan, Neurology – Sanbo Brain Hospital; Mengyi Guo, Neurology – Sanbo Brain Hospital; Guoming Luan, Neurology – Sanbo Brain Hospital; Chongyang Tang, Neurology – Sanbo Brain Hospital; Pengfei Teng, Neurology – Sanbo Brain Hospital; Jing Wang, Neurology – Sanbo Brain Hospital; Xiongfei Wang, Neurology – Sanbo Brain Hospital; Zhonghua Xiong, Neurology – Sanbo Brain Hospital; Yujiao Yang, Neurology – Sanbo Brain Hospital; Feng Zhai, Neurology – Sanbo Brain Hospital; Jing Zhang, Neurology – Sanbo Brain Hospital; Yifan Zhang, Neurology – Sanbo Brain Hospital; Jian Zhou, Neurology – Sanbo Brain Hospital
Rationale:
Mesial temporal lobe epilepsy without hippocampal sclerosis (no-HS MTLE) refers to those MTLE patients who have neither MRI lesions nor definite pathological evidence of hippocampal sclerosis. They are usually demonstrated having resistance to antiepileptic drugs, complicated preoperative examinations, and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator which acts as a seizure terminator in brain. The role of adenosine in no-HS MTLE is still unclear. Further research to explore the etiology and pathogenesis of no-HS MTLE may help to find new therapeutic targets.
Methods:
In surgically resected hippocampal specimens, we examined the maladaptive changes of adenosine system of patients with no-HS MTLE. In order to better understand the dysregulation of adenosine pathway in no-HS MTLE, we further developed a rat model based on the induction of focal cortical lesion through a prenatal freeze injury.
Results:
In this study, we first examined the adenosine system in no-HS MTLE patients which lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolizing enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of the neuronal A1 receptors (A1Rs) in the hippocampus. In no-HS MTLE model rats, the transition process of ADK from the initial neuronal expression to a distinct adult pattern of glial expression in hippocampus was significantly delayed.
Conclusions:
Ectopic expression of neuronal ADK might be a pathological hallmark of the no-HS MTLE. Maladaptive changes in adenosine metabolism might represent a novel target for therapeutic intervention of no-HS MTLE.
Funding:
This project was supported by grants from the National Natural Science Foundation of China (81571275); the National Institutes of Health (grant nos. NS065957 and NS103740).