Immunohistochemical Study for Expression of cFos, pERK1/2 and pAkt Proteins in a Macrosphere Animal Model for Permanent Focal Brain Ischemic Injury

ABSTRACT

PURPOSE: Recently, a new animal model for permanent focal brain ischemia using macrospheres was developed wherein the hypothalamic area was free from ischemic injury. The purpose of this study was to evaluate spatiotemporal changes in the expressions of cFos, pERK, and pAkt proteins in the macrosphere model. METHOD: Three or four macrospheres were injected into the internal carotid artery after ligation of the external carotid artery to induce permanent focal brain ischemic injury. RESULT: Twenty-four hours after macrosphere injection, 2,3,5-Triphenyltetrazlium (TTC) staining showed a marked ischemic injury in the blood supply territory of the middle cerebral artery, for example, the cerebral cortex and striatum. Furthermore, TUNEL staining revealed apoptotic cell death in the ischemic injury region of the cerebral cortex and striatum. Expression of the cFos protein was significant in the penumbral zone, but not in the ischemic core of the cortex and striatum, two and six hours after ischemic insult. A transient prominent expression of the pERK1/2 protein was noted in the penumbral zone of the cortex and striatum two hours after injection of macrospheres. In contrast, there was a strong immunoreactivity for the pAkt protein in the ischemic core, but not in the penumbral zone of the cortex and striatum, six hours after ischemic injury. CONCLUSION: The above results suggest that early expressions of cFos, pERK1/2, and pAkt proteins take part in different signaling cascades for cell survival or death in macrosphere animal model of permanent focal brain ischemic injury.