The role of CDK5 activation in neuronal death and angiogenesis after ischemic stroke

• Project/Area Number: 22590942
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Nippon Medical School
• Principal Investigator: NAGATA Chikako (NITO Chikako) 日本医科大学, 医学部, 講師 (30409172)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 局所脳虚血 / Cdk5 / 神経細胞死 / 血液脳関門障害 / 血管新生

Research Abstract

The aim of this study was to clarify the role of Cdk 5 activation in neuronal death and angiogenesis in the brain after transient focal cerebral ischemia (tFCI). After reperfusion, both Cdk5 activation and p25/p35 expression were significantly increased at 6 h compared with the control and decreased the expression at 3 days and recovererd at 7 days as detected by immunoblotting. p25/p35 was significantly upregulated in neurons in the ischemic area at 1 day and also upregulated in microvessels in the ischemic boundary zone from 3 to 7 days after reperfusion. Changes in BBB leakage indicated that BBB breakdown significantly increased 3 days after reperfusion. These findings suggest that Cdk 5 may be related to not only neuronal death but also angiogenesis after tFCI and can be a target for antiangiogenic therapy.

Research Products

• [Journal Article] Involvement of Mitogen-Activated Protein Kinase Pathways in Expression of the Water Channel Protein Aquaporin-4 after Ischemia in Rat Cortical Astrocytes (2012)
  • Author(s): Nito C, Kamada H, Endo H, NarasimhanP, Lee Y-S, Chan PH
  • Journal Title: J Neurotrauma Volume: 29 Pages: 2404-12
• [Journal Article] FK506 ameliorates oxidative damage and protects rat brain following transient focal cerebral ischemia (2011)
  • Author(s): Nito C, Ueda M, Inaba T, Katsura K, Katayama Y
  • Journal Title: Neurol Res Volume: 33 Pages: 881-9
• [Journal Article] Neuroprotective Effect of an Antioxidant in Ischemic Stroke: Involvement of Neuronal Death Signaling and Blood-brain Barrier Disruption (2011)
  • Author(s): Nito C, Katayama Y
  • Journal Title: J Nippon Med Sch Volume: 78 Pages: 60-62
  • NAID: 130004147093
• [Journal Article] FK506 ameliorates oxidative damage and protects rat brain following transient focal cerebral ischemia (2011)
  • Author(s): Chikako Nito
  • Journal Title: Neurological Research Volume: 33 Pages: 881-889
  • Peer Reviewed
• [Journal Article] Neuroprotective Effect of an Antioxidant in Ischemic Stroke : Involvement of Neuronal Death Signaling and Blood-brain Barrier Disruption (2011)
  • Author(s): Chikako Nito
  • Journal Title: J Nippon Med Sch. Volume: 78 Pages: 60-62
  • NAID: 130004147093
• [Presentation] Neuroprotective effects of nicergoline against brain damage in a rat model of permanent focal cerebral ischemia (2012)
  • Author(s): Nito C, Inaba T, Ueda M, Saito T, Katayama Y
  • Organizer: 42nd Annual Meeting of Society for Neuroscience
  • Place of Presentation: New Orleans, USA
• [Presentation] The neuroprotective effects of Post-treatment with atorvastatin reduces inflammatory responses and protects rat brain after transient focal ischemia (2012)
  • Author(s): Saito T, Nito C, Ueda M, Inaba T, Kamiya F, Katayama Y
  • Organizer: 42nd Annual Meeting of Society for Neuroscience
  • Place of Presentation: New Orleans, USA
• [Presentation] A free radical scavenger combined with mild hypothermia attenuates ischemic brain damage by suppressing matrix metalloproteinase 9 (2011)
  • Author(s): Chikako Nito
  • Organizer: The 5th Korean-Japanese Joint Stroke Conference
  • Place of Presentation: Gyeongju, Korea
  • Year and Date: 2011-10-15
• [Presentation] Combination therapy with edaravone and mild hypothermia prevents MMP-9 activiation and neurovascular injury after focal cerebral ischemia in rats (2011)
  • Author(s): Chikako Nito
  • Organizer: The 25th Internal Symposium on Cerebral Blood Flow, Metabolism, and Function
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-05-15
• [Presentation] Combination therapy with edaravone and mild hypothermia prevents MMP-9activiation and neurovascular injury after focal cerebral ischemia in rats (2011)
  • Author(s): Nito C, Ueda M, Inaba T, Okubo S, Nomur K, Kamiya F, Ohta S, Katayama Y
  • Organizer: The 25th Internal Symposium on Cerebral Blood Flow, Metabolism, and Function
  • Place of Presentation: Barcelona, Spain
• [Presentation] A free radical scavenger combined with mild hypothermia ameriolates ischemic brain damage by suppressing matrix metalloproteinase 9 (2010)
  • Author(s): Chikako Nito
  • Organizer: 40th Annual Meeting of Neuroscience
  • Place of Presentation: Chicago, U.S.A.
  • Year and Date: 2010-11-15
• [Presentation] A free radical scavenger and mild hypothemia for brain damage after focal ischemeia-Effects on MMP activation and blood-brain barrier disruption (2010)
  • Author(s): Chikako Nito-Nagata
  • Organizer: The 1st Forum on Cerebral Blood Flow, Metabolism and Function Kyoto 2010
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-10-15
• [Presentation] A free radical scavenger combined with mild hypothermia attenuates ischemic brain damage by suppressing matrix metalloproteinase 9 (2010)
  • Author(s): Nito C, Ueda M, Inaba T, Nomura K, Katayama Y
  • Organizer: 40th Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Book] Therapeutic Windowを広げる時間を止める:t-PAと脳保護薬の併用の可能性.分子脳血管病第10巻第1号 (2010)
  • Author(s): 仁藤智香子、片山泰朗
  • Publisher: 先端医学社