Inflammatory mechanisms of periventricular leukomalicia

• Project/Area Number: 23591515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo (2013); Kyorin University (2011-2012)
• Principal Investigator: OKA Akira 東京大学, 医学部附属病院, 教授 (00251273)
• Co-Investigator(Kenkyū-buntansha): 伊藤 雅之 独立行政法人国立精神神経医療研究センター, 室長 (50243407)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 脳室周囲白質軟化症 / 脳性麻痺 / 敗血症 / 周産期医学 / 脳障害 / 新生児敗血症 / リポ多糖 / 黄色ブドウ球菌 / 周産期脳障害

Research Abstract

In order to investigate the role of infection and inflammation in the pathogenesis of periventricular leukomalacia (PVL), an important cause of cerebral palsy, models of neonatal sepsis were developed in rat pups. The intraperitoneal administration of lipopolysaccharides from E. Coli to neonatal rats caused PVL-like lesions in periventricular white matter, where the infiltration of inflammatory cells as well as the reduction of oligodendrocytes was observed, leading to the impaired myelination. These findings were regarded to be consistent with the damages of immature oligodendrocytes observed in human PVL. In another experimental model of neonatal sepsis of Gram-positive bacteria, the intraperitoneal injection of a toxin derived from Staphylococcus aureus caused neuronal loss in hippocampus, lacking lesion of cerebral white matter. Therefore, neonatal sepsis caused distinct lesions in neonatal brains, depending on the species of bacteria and related toxins.

Research Products

• [Journal Article] Hyaluronic acid concentration in Fontan circulation : Correlation with hepatic function and portal vein hemodynamics (2014)
  • Author(s): Hayashi T, Inuzuka R, Shindo T, Hirata Y, Shimizu N, Oka A.
  • Journal Title: Pediatr Cardiol Volume: 35 Pages: 608-15
• [Journal Article] Chimerism of buccal membrane cells in a monochorionic dizygotic twin (2014)
  • Author(s): Fumoto S, Hosoi K, Ohnishi H, Hoshina H, Yan K, Saji H, Oka A.
  • Journal Title: Pediatrics Volume: 133
• [Journal Article] Nationwide survey of Arima syndrome : revised diagnostic criteria from epidemiological analysis (2014)
  • Author(s): Itoh M, Iwasaki Y, Ohno K, Inoue T, Hayashi M, Ito S, Matsuzaka T, Ide S, Arima M.
  • Journal Title: Brain Dev Volume: 36 Pages: 388-93
• [Journal Article] LOX-1 Is a Novel Therapeutic Target in Neonatal Hypoxic-Ischemic Encephalopathy (2014)
  • Author(s): Akamatsu T, Dai H, Mizuguchi M, Goto Y, Oka A, Itoh M.
  • Journal Title: Am J Pathol Volume: 184 Pages: 1843-52
• [Journal Article] Serum hyaluronic acid concentration in Fontan circulation: correlation with hepatic function and portal vein hemodynamics. (2014)
  • Author(s): Hayashi T1, Inuzuka R, Shindo T, Hirata Y, Shimizu N, Oka A.
  • Journal Title: Pediatric Cardiology Volume: 35 Issue: 4 Pages: 608-615
  • DOI: 10.1007/s00246-013-0827-9
  • Peer Reviewed
• [Journal Article] Chimerism of buccal membrane cells in a monochorionic dizygotic twin. (2014)
  • Author(s): Fumoto S, Hosoi K, Ohnishi H, Hoshina H, Yan K, Saji H, Oka A.
  • Journal Title: Pediatrics Volume: 133 Issue: 4 Pages: e1097-e1100
  • DOI: 10.1542/peds.2013-1938
  • Peer Reviewed
• [Journal Article] Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension (2013)
  • Author(s): Kataoka M, Aimi Y, Yanagisawa R, Ono M, Oka A, Fukuda K, Yoshino H, Satoh T, Gamou S.
  • Journal Title: Genet Med Volume: 15 Pages: 941-7
• [Journal Article] 部画像診断 (2013)
  • Author(s): 岡明
  • Journal Title: 周産期医学 Volume: 43 Pages: 186-190
• [Journal Article] サイトメガロウイルス感染症 (2013)
  • Author(s): 岡明
  • Journal Title: 産婦人科の実際 Volume: 62 Pages: 1467-1472
• [Journal Article] Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes (2012)
  • Author(s): Hoshino A, Saitoh M, Oka A, Okumura A, Kubota M, Saito Y, Takanashi JI, Hirose S, Yamagata T, Yamanouchi H, Mizuguchi M.
  • Journal Title: Brain Dev Volume: 34 Pages: 337-343
  • NAID: 10031050639
• [Journal Article] Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis (2012)
  • Author(s): Fukumura S, Saito Y, Saito T, Komaki H, Nakagawa E, Sugai K, Sasaki M, Oka A, Takamisawa I.
  • Journal Title: Dev Med Child Neurol Volume: 54 Pages: 663-666
• [Journal Article] Methyl CpG-binding protein isoform MeCP2_e2 is dispensable for Rett syndrome phenotypes but essential for embryo viability and placenta development (2012)
  • Author(s): Itoh M, Tahimic CG, Ide S, Otsuki A, Sasaoka T, Noguchi S, Oshimura M, Goto Y, Kurimasa A.
  • Journal Title: J Biol Chem Volume: 287 Pages: 13859-67
• [Journal Article] Abnormal maturation and differentiation of neocortical neurons in epileptogenic cortical malformation : unique distribution of layer-specific marker cells of focal cortical dysplasia and hemimegalencephaly (2012)
  • Author(s): Arai A, Saito T, Hanai S, Sukigara S, Nabatame S, Otsuki T, Nakagawa E, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sugai K, Sasaki M, Goto Y, Itoh M.
  • Journal Title: Brain Res Volume: 1470 Pages: 89-97
• [Journal Article] Delayed maturation and differentiation of neurons in focal cortical dysplasia with the transmantle sign : analysis of layer-specific marker expression (2012)
  • Author(s): Sakakibara T, Sukigara S, Saito T, Otsuki T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sato N, Kimura Y, Nakagawa E, Sugai K, Sasaki M, Goto Y, Itoh M.
  • Journal Title: J Neuropathol Exp Neurol Volume: 71 Pages: 741-9
• [Journal Article] Novel pathological abnormalities of deep brain structures including dysplastic neurons in anterior striatum associated with focal cortical dysplasia in epilepsy (2012)
  • Author(s): Kaido T, Otsuki T, Kakita A, Sugai K, Saito Y, Sakakibara T, Takahashi A, Kaneko Y, Saito Y, Takahashi H, Honda R, Nakagawa E, Sasaki M, Itoh M.
  • Journal Title: J Neurosurg Pediatr Volume: 10 Pages: 217-25
• [Journal Article] Imbalance of interneuron distribution between neocortex and basal ganglia : consideration of epileptogenesis of focal cortical dysplasia (2012)
  • Author(s): Sakakibara T, Sukigara S, Otsuki T, Takahashi A, Kaneko Y, Kaido T, Saito Y, Sato N, Nakagawa E, Sugai K, Sasaki M, Goto Y, Itoh M.
  • Journal Title: J Neurol Sci Volume: 323 Pages: 128-33
• [Journal Article] Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes. (2012)
  • Author(s): Hoshino A, Saitoh M, Oka A, Okumura A, Kubota M, Saito Y, Takanashi JI, Hirose S, Yamagata T, Yamanouchi H, Mizuguchi M.
  • Journal Title: Brain Dev Volume: 34 Pages: 337-343
  • NAID: 10031050639
  • Peer Reviewed
• [Journal Article] Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis. (2012)
  • Author(s): Fukumura S, Saito Y, Saito T, Komaki H, Nakagawa E, Sugai K, Sasaki M, Oka A, Takamisawa I
  • Journal Title: Dev Med Child Neurol Volume: 54 Issue: 7 Pages: 663-666
  • DOI: 10.1111/j.1469-8749.2011.04170.x
  • Peer Reviewed
• [Journal Article] Interstitial deletion of 13q14.13-q32.3 presenting with Arima syndrome and bilateral retinoblastoma (2011)
  • Author(s): Takahashi K, Oka A, Mizuguchi M, Saitoh M, Takita J, Sato A, Mimaki M, Kato M, Ogawa S, Igarashi T.
  • Journal Title: Brain Dev Volume: 33 Pages: 353-6
  • NAID: 10029561455
• [Journal Article] Japanese Congenital Cytomegalovirus Study Group. Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper : feasibility and outcomes from a multicentre study (2011)
  • Author(s): Koyano S, Inoue N, Oka A, Moriuchi H, Asano K, Ito Y, Yamada H, Yoshikawa T, Suzutani T
  • Journal Title: BMJ Open Volume: 1
• [Journal Article] Interstitial deletion of 13q14.13-q32.3 presenting with Arima syndrome and bilateral retinoblastoma (2011)
  • Author(s): Takahashi K, Oka A, Mizuguchi M, Saitoh M, Takita J, Sato A, et al
  • Journal Title: Brain Dev Volume: 33 Issue: 4 Pages: 353-356
  • DOI: 10.1016/j.braindev.2010.06.014
  • NAID: 10029561455
  • Peer Reviewed
• [Journal Article] Japanese Congenital Cytomegalovirus Study Group. Screening for congenital cytomegalovirus infection using newborn urine samples collected on filter paper: feasibility and outcomes from a multicentre study. (2011)
  • Author(s): .Koyano S, Inoue N, Oka A, Moriuchi H, Asano K, Ito Y, Yamada H, Yoshikawa T, Suzutani T;
  • Journal Title: BMJ Open Volume: 1 Issue: 1 Pages: e000118-e000118
  • DOI: 10.1136/bmjopen-2011-000118
  • Peer Reviewed
• [Journal Article] 脳室周囲白質軟化症 (2011)
  • Author(s): 岡明
  • Journal Title: Fetal & Neonatal Medicine Volume: 3
• [Journal Article] 頭部ＭＲＩ (2011)
  • Author(s): 岡明
  • Journal Title: 周産期医学 Volume: 41 Pages: 1441-1445
• [Presentation] Cerebral white matter injury caused by lipopolysaccharides in immature rat brains. A model of periventricular leukomalacia by neonatal sepsis. (2012)
  • Author(s): Shimazaki M, Miyata Y, Oka A.
  • Organizer: 12th International Child Neurology Congress
  • Place of Presentation: Brisbane
• [Presentation] わが国の脳性麻痺児の現況と課題
  • Author(s): 岡 明
  • Organizer: 第72回日本公衆衛生学会
  • Place of Presentation: 三重
  • Invited
• [Presentation] 脳の可塑性とてんかん
  • Author(s): 岡 明
  • Organizer: 埼玉てんかん治療研究会
  • Place of Presentation: さいたま
  • Invited
• [Presentation] 補償審査委員会からみた現状、問題点と効果的な診断書作成の助言
  • Author(s): 岡明
  • Organizer: 第55回日本小児神経学会
  • Place of Presentation: 大分
  • Invited
• [Book] 先天性サイトメガロウイルス感染症の現状と臨床像 小児神経学の進歩 第40集 (2011)
  • Author(s): 岡明
  • Publisher: 診断と治療社