Ischemia leads to a complex sequence of events culminating in the loss of functional integrity of the nervous system and, ultimately, in neuronal cell death. Intracellular accumulation of calcium ions following ischemia may alter protein kinase C
(PKC)
activity. But nature of change of the PKC activity depending on duration and degrec of ischemia is not well understood.
To understand the effect of the experimental focal ischemia on expression of PKC isozyme, we investigated the expression of PKC γ, β, α immunocytochemically and activities of cytochrome oxidase (CO) histochemically in focal ischemic brain of
the
rat.
Two groups of focal ischemic infarction were produced in two groups of Sprague Dawley rats (200-300gm) : Group I, Clip compression of left middle cerebral artery (MCA) for 10min and release and sacrificed 48hr later ; Group II, Electric
coagulation
of
left MCA and killed 2-24hr later.
In the group I, CO activity and immunoreactivity (IR) for PKC γ andβ were decreased generally in the left MCA territory, especially in layers II through IV of ischemic cortex. In the group II, decrease of CO activities and marked increase of
three PKC
isozyme IRs were noted in the layers I through VI. The isozymes displayed different localization in the control cortex, but the IRs of three isozymes markedly increased in the ischemic region, so that the difference among IR patterns disappeared.
Although vacuolation and decrease of number of IR neuron were noted, there were remaining IR pyramidal neurons around vacuole in layers IV/V showing dense immuostaining in the cell body and apical dendrite.
These results indicate that 10min acute ischemia inhibits activity of PKC γ and β and that prolonged ischemia longer than 2hr induces the expression of three PKC isozymes. Inhibition and possible induction of PKC are proposed to represent a
critical
step during ischemic neuronal injury.
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