Upregulation of HMGB1, toll-like receptor and RAGE in human Rasmussen's encephalitis.
Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by uni-hemispheric inflammation, progressive neurological deficits and intractable focal epilepsy. The pathogenesis of RE is still enigmatic. Activation of endogenous high-mobility group box-1 (HMGB1) and Toll-like receptor (TLR) has been proved to be with pro-inflammatory as well as pro-convulsant effects. We hypothesized that the epileptogenic mechanisms underlying RE are related to activation of HMGB1/TLR signaling. Immunnohistochemistry approach was used to examine the expression of HMGB1, TLR2, TLR4, receptor for advanced glycation end products (RAGE) in surgically resected human epileptic cortical specimens from RE (n=12), and compared that with control cortical issue (n=6). HMGB1 was ubiquitously detected in nuclei of astrocytes while its receptors were not detected in control cortex specimens. Marked expression of the receptors were observed in the lesions of RE. In particular, HMGB1 was in stead detected in cytoplasm of reactive astrocytes in RE cortex, predictive its release from glial cells. Significant greater HMGB1 and its receptors expression in RE vs. control was demonstrated by western blot. These results provide the novel evidence of intrinsic activation of these pro-inflammation pathways in RE, which suggest the specific targets in the treatment of epilepsy associated with RE.
Department of Neurosurgery, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
Guoming
G
Luan
Department of Brian Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
Qing
Q
Gao
Department of Neurosurgery, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
Feng
F
Zhai
Department of Brian Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China.
Yin
Y
Chen
Department of Brian Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China; Department of Neurology, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, China. Electronic address: tianfuli66@126.com.
Tianfu
T
Li
D000293:Adolescent; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D002525:Cerebellar Cortex / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000069279:Drug Resistant Epilepsy / Q000209:etiology*; D004569:Electroencephalography; D004660:Encephalitis / Q000150:complications* / Q000378:metabolism*; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism*; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012640:Seizures / Q000209:etiology; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation
C000593871:AGER protein, human; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D051193:Toll-Like Receptors
Epilepsy; HMGB1; Inflammation; Rasmussen encephalitis