Tenascin-C causes neuronal apoptosis after subarachnoid hemorrhage in rats.
The role of tenascin-C (TNC), a matricellular protein, in brain injury is unknown. The aim of this study was to examine if TNC causes neuronal apoptosis after subarachnoid hemorrhage (SAH), a deadly cerebrovascular disorder, using imatinib mesylate (a selective inhibitor of platelet-derived growth factor receptor [PDGFR] that is reported to suppress TNC induction) and recombinant TNC. SAH by endovascular perforation caused caspase-dependent neuronal apoptosis in the cerebral cortex irrespective of cerebral vasospasm development at 24 and 72 h post-SAH, associated with PDGFR activation, mitogen-activated protein kinases (MAPKs) activation, and TNC induction in rats. PDGFR inactivation by an intraperitoneal injection of imatinib mesylate prevented neuronal apoptosis, as well as MAPKs activation and TNC induction in the cerebral cortex at 24 h. A cisternal injection of recombinant TNC reactivated MAPKs and abolished anti-apoptotic effects of imatinib mesylate. The TNC injection also induced TNC itself in SAH brain, which may internally augment neuronal apoptosis after SAH. These findings suggest that TNC upregulation by PDGFR activation causes neuronal apoptosis via MAPK activation, and that the positive feedback mechanisms may exist to augment neuronal apoptosis after SAH. TNC-induced neuronal apoptosis would be a new target to improve outcome after SAH.
Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Masato
M
Shiba
Masashi
M
Fujimoto
Kyoko
K
Imanaka-Yoshida
Toshimichi
T
Yoshida
Waro
W
Taki
Hidenori
H
Suzuki
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001549:Benzamides / Q000494:pharmacology; D004195:Disease Models, Animal; D000068877:Imatinib Mesylate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism* / Q000473:pathology; D019063:Tenascin / Q000378:metabolism*; D020301:Vasospasm, Intracranial / Q000378:metabolism* / Q000473:pathology
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019063:Tenascin; D000068877:Imatinib Mesylate