High mobility group box 1 enhanced febrile seizures and acquired epilepsy in a rodent model of infantile febrile seizures

• Project/Area Number: 25461553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Ehime University
• Principal Investigator: Fukuda Mitsumasa 愛媛大学, 医学部附属病院, 准教授 (80274330)
• Co-Investigator(Kenkyū-buntansha): Suzuki Yuka 愛媛大学, 大学院医学系研究科, 寄附講座准教授 (00304634) ; Tanaka Junya 愛媛大学, 大学院医学系研究科, 教授 (70217040)
• Co-Investigator(Renkei-kenkyūsha): Ishizaki Yoshito 九州大学, 大学病院, 助教 (20572944)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 熱性痙攣 / 側頭葉てんかん / HMGB－１ / 分子標的 / ラット / 海馬 / 脳波 / アストログリア / HMGB1 / 熱性けいれん / 後天性てんかん / アストログリオーシス / てんかん / けいれん重積 / ヌクレオカイン / 海馬細胞障害 / 内側側頭葉てんかん

Outline of Final Research Achievements

We investigated the role of HMGB1 in febrile seizures (FS) and secondary acquired epilepsy associated with febrile status epilepticus using hyperthermia-induced seizures (HS) in immature rats, a model of human FS. HMGB1 enhanced HS, but did not induce any hippocampal damage. HMGB1 also enhanced acquired epilepsy after febrile status epilepticus using hyperthermia-induced seizures (HS), and histological analysis showed that astrocytes were significantly increased in the hippocampus and the corpus callosum in rats having acquired epilepsy. Our results indicate that infantile prolonged febrile seizures with HMGB1 overproduction could enhance adulthood epileptogenesis and might contribute to the development of mesial temporal lobe epilepsy. Further, astrogliosis also should play an important role in acquired epileptogenesis.

Research Products

• [Journal Article] Postnatal interleukin-1beta administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood (2015)
  • Author(s): Fukuda, M, Ishii, E, et al.
  • Journal Title: Metab Brain Dis Volume: in press Issue: 3 Pages: 813-819
  • DOI: 10.1007/s11011-014-9648-7
  • Peer Reviewed
• [Journal Article] KL-6 as a biomarker of respiratory complications in severely disabled children. (2015)
  • Author(s): Ochi F, Fukuda M, Ohmori H, Yano Y, Wakamoto H, Suzuki Y, Ishii E.
  • Journal Title: Pediatr Int. Volume: in press Issue: 3 Pages: 439-442
  • DOI: 10.1111/ped.12537
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Carnitine deficiency: risk factors and incidence in children with epilepsy. (2015)
  • Author(s): Fukuda M, Kawabe M, Takehara M, IWANO S, Kuwabara K, Kikuchi C, Wakamoto H, Morimoto T, Suzuki Y, Ishii E.
  • Journal Title: Bra Dev. Volume: in press Issue: 8 Pages: 790-796
  • DOI: 10.1016/j.braindev.2014.12.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats. (2014)
  • Author(s): Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E.
  • Journal Title: Acta Neurol Belg. Volume: 114 Issue: 3 Pages: 179-185
  • DOI: 10.1007/s13760-013-0246-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats. (2014)
  • Author(s): Fukuda M, Hino H, Suzuki Y, Takahashi H, Morimoto T, Ishii E.
  • Journal Title: Acta Neurol Belg Volume: (in press)
  • Peer Reviewed
• [Presentation] High mobility group box 1 after infantile experimental prolonged febrile seizures enhances acquired epileptogenesis in adulthood (2015)
  • Author(s): Ito M, Fukuda M, Yano H, Yano Y, Tanaka J, Ishii E
  • Organizer: 第49回日本てんかん学会学術集会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 2015-10-30
• [Presentation] Toll-like receptor 3 activation enhances hyperthermia-induced seizures in immature rats. (2015)
  • Author(s): Fukuda M, Ito M, Yano Y, Sakuma H, Hayashi M
  • Organizer: 第57回日本小児神経科学会学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2015-05-28
• [Presentation] Postnatal interleukin-1β after experimental prolonged febrile seizures enhances epileptogenesis in adulthood (2014)
  • Author(s): Mitsumasa Fukuda, Masanori Ito, Yoshiaki Yano, Hisaaki Takahashi, Takehiko Morimoto, Yuka Suzuki, and Eiichi Ishii
  • Organizer: the 10th Asian & Oceanian Epilepsy Congress
  • Place of Presentation: Singapore
  • Year and Date: 2014-08-07 – 2014-08-10
• [Presentation] High mobility group box 1 enhances hyperthermia-induced seizures in developing rats. (2014)
  • Author(s): Masanori Ito, Mitsumasa Fukuda, Yoshiaki Yano, Hisaaki Takahashi, Yuka Suzuki, Takehiko Morimoto, and Eiichi Ishii
  • Organizer: the 10th Asian & Oceanian Epilepsy Congress
  • Place of Presentation: Singapore
  • Year and Date: 2014-08-07 – 2014-08-10
• [Presentation] High mobility group box 1 enhances hyperthermia-induced seizures in developing rats.
  • Author(s): Masanori Ito, Mitsumasa Fukuda, Yoshiaki Yano, Hisaaki Takahashi, Yuka Suzuki, Takehiko Morimoto, and Eiichi Ishii
  • Organizer: 7th IGAKUKEN International Symposium
  • Place of Presentation: Tokyo
• [Presentation] Animal models for the study of febrile seizures and acquired epileptogenesis.
  • Author(s): Mitsumasa Fukuda, Masanori Ito, Yoshiaki Yano, Yuka Suzuki, Hisaaki Takahashi, Takehiko Morimoto, Eiichi Ishii
  • Organizer: 7th IGAKUKEN International Symposium
  • Place of Presentation: Tokyo
  • Invited
• [Book] 子どものけいれん・てんかんガイド、分担執筆『 熱性けいれんと憤怒けいれん』 (2013)
  • Author(s): 福田光成
  • Publisher: 中山書店