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

• Published in: Cellular and molecular neurobiology Vol. 31; no. 5; pp. 795 - 802
• Main Authors: Shimoke, Koji, Matsuki, Yoshinori, Fukunaga, Kenji, Matsumura, Yoshinobu, Fujita, Eriko, Sugihara, Kensuke, Nobuhara, Masamichi, Maruoka, Hiroki, Ikeuchi, Toshihiko, Kudo, Motoshige
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2011
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Brain Infarction - complications; Brain Infarction - pathology; Caspase 12 - metabolism; Cell Biology; Cell Nucleus - enzymology; Cerebral Cortex - pathology; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Heat-Shock Proteins - metabolism; Hippocampus - pathology; In Situ Nick-End Labeling; Intracranial Embolism - complications; Intracranial Embolism - pathology; Male; Models, Biological; Neurobiology; Neurons - enzymology; Neurons - pathology; Neurosciences; Original Research; Peptide Fragments - metabolism; Protein Transport; Rats; Rats, Wistar; Staining and Labeling; Stress, Physiological; Thrombosis - complications; Thrombosis - pathology; Translocation; Nucleus; Cerebral infarction; Caspase-12; Endoplasmic reticulum stress; Apoptosis
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-011-9687-0

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.