Appearance of Nuclear-sorted Caspase-12 Fragments in Cerebral Cortical and Hippocampal Neurons in Rats Damaged by Autologous Blood Clot Embolic Brain Infarctions

  • Koji Shimoke
  • Yoshinori Matsuki
  • Kenji Fukunaga
  • Yoshinobu Matsumura
  • Eriko Fujita
  • Kensuke Sugihara
  • Masamichi Nobuhara
  • Hiroki Maruoka
  • Toshihiko Ikeuchi
  • Motoshige Kudo
Original Research


Following endoplasmic reticulum (ER) stress, cerebral infarctions have been reported to involve an apoptotic process, including the activation of the caspase cascade. To confirm whether fragmented caspase-12, which is activated by cleavage and is detectable during ER stress, is also involved in embolic cerebral infarctions in rats, we adopted an autologous blood clot model for the analysis of cerebral infarctions. We performed experiments in rats with brain infarctions, which are closely related to embolic cerebral infarctions. We utilized a homologous blood clot, i.e., natural materials, to form the infarct area. Our findings reveal that caspase-12 is fragmented when infarct areas form in cerebral cortical neurons. Interestingly, we observed that these fragments translocated to the nuclei of not only cerebral cortical neurons but hippocampal neurons. We further found that glucose-regulated protein 78 (GRP78), a marker of ER stress, is up-regulated in both cerebral cortical and hippocampal neurons during cerebral infarction. This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats.


Caspase-12 Endoplasmic reticulum stress Translocation Nucleus Cerebral infarction Apoptosis 



Endoplasmic reticulum


Glucose-regulated protein 78


B cell/lymphoma-2


Middle cerebral artery occlusion


Hematoxylin and eosin


Terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labeling


Unfolded protein response


Phosphate-buffered saline



This study was supported by grants-in-aid for scientific research (KAKENHI 21570152) and the “Strategic Project to Support the Formation of Research Bases at Private Universities (SENRYAKU)” (2008–2012) from MEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan). This work was also supported by the Kansai University Special Research Fund, 2009.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Koji Shimoke
    • 1
  • Yoshinori Matsuki
    • 2
    • 3
  • Kenji Fukunaga
    • 4
  • Yoshinobu Matsumura
    • 4
  • Eriko Fujita
    • 5
  • Kensuke Sugihara
    • 1
  • Masamichi Nobuhara
    • 1
  • Hiroki Maruoka
    • 1
    • 6
  • Toshihiko Ikeuchi
    • 1
  • Motoshige Kudo
    • 2
  1. 1.Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and BioengineeringKansai UniversitySuitaJapan
  2. 2.Department of PathologyTokyo Medical UniversityTokyoJapan
  3. 3.Department of PathologyMitsui Memorial HospitalTokyoJapan
  4. 4.Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and BioengineeringKansai UniversitySuitaJapan
  5. 5.Division of Differentiation and Development, Department of Inherited Metabolic DisordersNational Institute of Neuroscience, NCNPTokyoJapan
  6. 6.Technology Research Laboratory, KURABONeyagawaJapan

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