title: Upregulations of CRH and CRHR1 in the Epileptogenic Tissues of Patients with Intractable Infantile Spasms.
abstract: OBJECTIVE
  Infantile spasms (IS) are an age-specific epileptic syndrome with specific clinical symptom and electroencephalogram (EEG) features, lacking treatment options, and a poor prognosis. Excessive endogenous corticotropin-releasing hormone (CRH) in infant brain might result in IS. However, the data from human IS are limited. In our study, we investigated the expressions of CRH and its receptor type 1 (CRHR1) in surgical tissues from patients with IS and autopsy controls.
  
  
  METHODS
  Specimens surgically removed from 17 patients with IS, and six autopsy controls were included in the study. Real-time PCR, Western blotting, and immunostaining were used to detect the expressions of mRNA, protein expression, and distribution. The correlation between variates was analyzed by Spearman rank correlation.
  
  
  RESULTS
  The expressions of CRH and CRHR1 were significantly upregulated in the epileptogenic tissues of IS patients compared with the control group. CRH was distributed mainly in neurons, while CRHR1 was distributed in neurons, astrocytes, and microglia. The expression levels of CRH and CRHR1 were positively correlated with the frequency of epileptic spasms. Moreover, the expression of protein kinase C (PKC), which was an important downstream factor of CRHR1, was significantly upregulated in the epileptogenic tissues of patients with IS and was positively correlated with the CRHR1 expression levels and the frequency of epileptic spasms.
  
  
  CONCLUSIONS
  These results suggest that the CRH signal transduction pathway might participate in the epileptogenesis of IS, supporting the hypothesis that CRH is related to the pathogenesis of IS.
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Huan-Ran
authors.initials: HR
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhen-Le
authors.initials: ZL
authors.lastname: Zang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Second affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D001344:Autopsy; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D002648:Child; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013036:Spasms, Infantile / Q000000981:diagnostic imaging / Q000473:pathology*; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
chemical_list: D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C051774:neurofilament protein H; D003346:Corticotropin-Releasing Hormone; D011493:Protein Kinase C
keywords: Corticotrophin-releasing hormone receptor 1 (CRHR1); Corticotropin-releasing hormone (CRH); Infantile spasms (IS); Protein Kinase C (PKC)