Development of drug delivery system for central nervous system disease using with temperature control devise

2011 Fiscal Year Final Research Report

• Project/Area Number: 22659261
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Yamaguchi University
• Principal Investigator: SUZUKI Michiyasu 山口大学, 大学院・医学系研究科, 教授 (80196873)
• Project Period (FY): 2010 – 2011
• Keywords: 血液脳関門 / ニューロモデュレーションデバイス / 脳温

Research Abstract

Drug delivery system(DDS) through blood brain barrier(BBB) promises to enhance the effectiveness of medicine for nervous system diseases such as epilepsy and malignant brain tumors. In order to develop the DDS system, control of BBB permeability of molecules by alteration of temperature was analyzed. Tight junction of artificial BBB made from mouse endothelial cell was temporary opened at 15 degrees centigrade. And claudin5, one of the major structural proteins of the tight junction decreased the amount of expression at 15 degrees. Evans blue administered to a rat vein leaked to the brain surface when it was cooled. The increased permeability was reversible by the temperature control. Indocyanine green administered intravenously to an epilepsy patient appeared to the cooled area of brain surface at the surgery of temporal lobectomy. These results lead that the temperature control may modulate BBB permeability in a reversible fashion.

Research Products

• [Journal Article] Cooling of the Epileptic Focus Suppresses Seizures with Minimal Influence on Neurological Functions (2012)
  • Author(s): Fujii M, Inoue T, Nomura S, Maruta Y, He Y, Yamakawa T, Suzuki M
  • Journal Title: Epilepsia53 Pages: 485-493
  • Peer Reviewed
• [Journal Article] Intra-operative monitoring of lower extremity motor-evoked potentials by direct cortical stimulation (2012)
  • Author(s): Maruta Y, Fujii M, Imoto H, Nomura S, Oka F, Goto H, Shirao S, Yoshikawa K, Yoneda H, Ideguchi M, Suehiro E, Koizumi H, Ishihara H, Kato S, Kajiwara K, Suzuki M
  • Journal Title: Clin Neurophysiol. 2012[ Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Significance of differences between brain temperature and core temperature(delta T) during mild hypothermia (2011)
  • Author(s): Suehiro E, Fujisawa H, Koizumi H, Nomura S, Kajiwara K, Fujii M, Suzuki M
  • Journal Title: Neurol Med Chir Pages: 551-555
  • Peer Reviewed
• [Journal Article] Application of focal cerebral cooling for the treatment of intractable epilepsy (2010)
  • Author(s): Fujii M, Fujioka H, Oku T, Tanaka N, Imoto H, Maruta Y, Nomura S, Kajiwara K, Saito T, Yamakawa T, Yamakawa T, Suzuki M
  • Journal Title: Neurol Med Chir Pages: 839-844
  • Peer Reviewed
• [Journal Article] An implantable, focal brain cooling device suppresses nociceptive pain in rats (2010)
  • Author(s): Fujioka H, Fujii M, Koizumi H, Imoto H, Nomura S, Saito T, Yamakawa T, Suzuki M
  • Journal Title: Neurosci Res Volume: 66 Pages: 402-405
  • Peer Reviewed
• [Journal Article] Epileptiform discharges and neuronal plasticity in the acute peri-infarct cortex of rats (2010)
  • Author(s): Fujioka H, Kaneko H, Fujii M, Suzuki SS, Imoto H, Nomura S, Fujisawa H, Yamakawa T, Suzuki M
  • Journal Title: Neurol Res Volume: 32 Pages: 666-669
  • Peer Reviewed
• [Presentation] Cooling of the Epileptic Focus Suppresses Seizures with Minimal Influence on Neurological Functions. American Epilepsy Society (2011)
  • Author(s): Fujii M, Inoue T, Suzuki M
  • Organizer: Annual Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 20111201-5
• [Presentation] Alterative treatment of intractable epilepsy with focal brain cooling-A review of our past atudies- (2011)
  • Author(s): Fujii M, Inoue T, Suzuki M, Tokiwa T, Yamakawa T
  • Organizer: IEEE SMC
  • Place of Presentation: Anchorage(Alaska), USA
  • Year and Date: 20111009-12
• [Presentation] Development of a Focal Cerebral Cooling System for the Treatment of Intractable Epilepsy (2011)
  • Author(s): Takao Inoue, Masami Fujii, Michiyasu Suzuki
  • Organizer: IEEE SMC
  • Place of Presentation: Anchorage(Alaska), USA
  • Year and Date: 20111009-12
• [Presentation] The effect of focal brain cooling on epileptic discharges in rats-Frequency analysis of electroencephalography- (2011)
  • Author(s): Hiroyuki Kida, Masami Fujii, Takao Inoue, Yeting He, Yuichi Maruta, Sadahiro Nomura, Kazuhiro Taniguchi, Takuya Ichikawa, Takashi Saito, Michiyasu Suzuki
  • Organizer: IEEE SMC
  • Place of Presentation: Anchorage(Alaska), USA
  • Year and Date: 20111009-12
• [Presentation] Inhibitory effects of focal brain cooling for motor cortical seizures in cats and nonhuman primates (2011)
  • Author(s): noue T, He Y, Fujii M, Fujioka H, Tokiwa T, Kida H, Imoto H, Maruta Y, Nomura S, Yamakawa T, Suzuki M
  • Organizer: 29th International Epilepsy Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 20110828-0901
• [Presentation] Alterative treatment of intractable epilepsy with focal brain cooling (2011)
  • Author(s): Fujii M, Inoue T, Imoto H, Tanaka N, Oku T, Maruta Y, Koizumi H, Nomura S, Owada Y, Saito T, Yamakawa T, Tokiwa T, Yamakawa T, Suzuki M
  • Organizer: 29th International Epilepsy Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 20110828-0901
• [Presentation] Identification of epileptic focus with multi-channel near-infrared spectroscopic topography(optic topography). (2011)
  • Author(s): Maruta Y, Fujii M, Imoto H, Nomura S, Matsushige T, Ichiyama T, Yamakawa T, Suzuki M
  • Organizer: 29th International Epilepsy Congress
  • Place of Presentation: Rome, Italy
  • Year and Date: 20110828-0901