A5 Ischemic stroke (penumbra, excitotoxic cascade)

Topic

Brain tissue relies on constant cerebral blood flow to sustain its activity. In ischemic stroke, this cerebral blood flow drops regionally within a portion of the brain tissue—a direct extension of the inflow concept used to describe brain tissue blood supply in another model. This regional drop in cerebral blood flow compromises the tissue's cellular energy production, consistent with the energy balance used to describe brain tissue metabolism in another model. Within the brain tissue, neurons are the cells that directly suffer from this lack of cellular energy; without sufficient energy, the function of the neuronal sodium-potassium pump—the same pump defined in another model—is compromised.

When the neuronal sodium-potassium pump fails, the neuron can no longer maintain its normal ionic gradients; this energy failure triggers the excessive release of glutamate into the extracellular space surrounding the neuron. The excess glutamate causes sustained activation of a specific type of glutamate receptor on the neuronal membrane—following the kinetics used to describe glutamate receptor activation in another model—and this sustained activation leads to a massive influx of calcium into the neuron. The greater the amount of glutamate released and the longer the receptor remains active, the greater the calcium influx; this massive influx of calcium, known as excitotoxicity, is what directly compromises neuronal viability. This loss of neuronal viability does not occur uniformly across the affected brain tissue; depending on the severity of the drop in cerebral blood flow, a distinction is made within the tissue between an ischemic core—where the flow reduction is so severe that the neuron irreversibly loses viability—and a penumbra zone, where the flow reduction is less severe and the neuron can still be saved if cerebral tissue perfusion is restored in time.

Without timely intervention to restore cerebral tissue perfusion, the penumbra zone does not remain stable alongside the ischemic core: neurons in the penumbra progressively lose viability, and the penumbra zone is recruited into the ischemic core—meaning it becomes part of the core rather than remaining as salvageable tissue. The longer the delay in restoring cerebral tissue perfusion, the more of the penumbra zone is recruited into the ischemic core.

Each portion of the penumbra zone recruited into the ischemic core increases the final volume of the infarction within the brain tissue; consequently, the ultimate extent of brain tissue damage depends directly on the time elapsed before perfusion is restored. Therefore, the timely restoration of cerebral tissue perfusion determines how much of the penumbra zone is saved and, ultimately, limits the final volume of the infarction sustained by the brain tissue following an ischemic stroke.

ID:4287