Postischemic changes in the immunophilin FKBP12 in the rat brain

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Cerebral ischemia causes neuronal death, partly mediated by calcium influx.
• Tacrolimus (FK506) is an immunosuppressant that protects against ischemic neuronal damage.
• FK506-binding protein-12 (FKBP12) modulates intracellular calcium flux.

Purpose of the Study:

• To investigate the changes in FKBP12 expression following focal and global cerebral ischemia in a rat model.
• To determine the role of FKBP12 in neuronal survival and death after ischemic injury.
• To explore FKBP12 involvement in the inflammatory response within the infarcted area.

Main Methods:

• Focal cerebral ischemia induced by middle cerebral artery occlusion (1 hour).
• Global cerebral ischemia induced by carotid artery occlusion and hypotension (10 minutes).
• Immunohistochemistry performed on brain sections at various time points post-reperfusion (4 hours to 7 days).

Main Results:

• FKBP12 immunoreactivity decreased in the ischemic core but increased in penumbra neurons after focal ischemia.
• Following global ischemia, CA1 hippocampal neurons showed decreased FKBP12, with a transient increase in some neurons.
• Leukocytes and macrophages within the infarct area exhibited FKBP12 immunoreactivity, while glial cells did not.

Conclusions:

• FKBP12 expression dynamics correlate with neuronal survival and death following cerebral ischemia.
• FKBP12 is upregulated in less severely injured neurons, suggesting a neuroprotective role.
• FKBP12 participates in the inflammatory response associated with cerebral infarction.