The Focal-Focal Preconditioning Effect of Photothrombotic Impact on the Signaling Protein Profile in the Penumbra Surrounding the Ischemic Core Induced by Another Photothrombotic Impact

摘要

Ischemic tolerance is the establishment of brain resistance to severe ischemic damage by a mild preconditioning stimulus, insufficient to irreversible tissue damage, but capable of initiating a defense response. We developed the model of focal-focal ischemic tolerance, in which the first local photothrombotic infarct (PTI) in the rat brain cortex reduced the infarct caused by second PTI applied to the contralateral cortex of the same rat 7 days later. Using antibody microarrays, we compared protein profiles in the penumbra surrounding the PTI core after single and double PTI. We observed up- or downregulation of several dozens of proteins that are aimed at neurodegeneration or neuroprotection. Both single and double PTI induced damaging processes in the rat cerebral cortex that included over-expression of various pro-apoptotic and signaling proteins and downregulation of other signaling proteins and regulators of proliferation, some components of actin, intermediate fiber and microtubular cytoskeletons, and proteins involved in vesicle transport and synaptic transmission. The simultaneous protective processes included the upregulation of different signaling and anti-apoptotic proteins, stimulators of proliferation, and proteins involved in remodeling of actin cytoskeleton. The elevated expression of some signaling proteins, such as calcium-dependent PLC gamma 1, PKV alpha 1, CaMKII alpha, calnexin, and calreticulin was preserved after double PTI. Less pro-survival proteins were downregulated in the penumbra after double than single impact.