Abstract
Cardiac arrest induces the cessation of cerebral blood flow, which can result in brain damage. The primary intervention to salvage the brain under such a pathological condition is to restore the cerebral blood flow to the ischemic region. Ischemia is defined as a reduction in blood flow to a level that is sufficient to alter normal cellular function. Brain tissue is highly sensitive to ischemia, such that even brief ischemic periods in neurons can initiate a complex sequence of events that may ultimately culminate in cell death. However, paradoxically, restoration of blood flow can cause additional damage and exacerbate the neurocognitive deficits in patients who suffered a brain ischemic event, which is a phenomenon referred to as “reperfusion injury.” Transient brain ischemia following cardiac arrest results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation, and apoptosis. The pathophysiology of post-cardiac arrest brain injury involves a complex cascade of molecular events, most of which remain unknown. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. Mitochondrial dysfunction based on the mitochondrial permeability transition after reperfusion, particularly involving the calcineurin/immunophilin signal transduction pathway, appears to play a pivotal role in the induction of neuronal cell death. The aim of this article is to discuss the underlying pathophysiology of brain damage, which is a devastating pathological condition, and highlight the central signal transduction pathway involved in brain damage, which reveals potential targets for therapeutic intervention.
Highlights
Pathophysiology for neurocritical care Hiroyuki Uchino1*, Yukihiko Ogihara1, Hidekimi Fukui1, Miyuki Chijiiwa1, Shusuke Sekine1, Naomi Hara1
L Abstract C Cardiac arrest induces the cessation of cerebral blood flow, which can result in brain damage
We previously demonstrated that immunosuppressants interacting with the calcineurin/immunophilin signal transduction pathway show potent neuroprotective effects in several animal models of ischemic brain damage, and these effects are considered to be separate from their action on immunocompetent cells [2,3,4,5,6]
Summary
IC Reperfusion Tinjury R Fig. 1 Pathophysiology of post-cardiac arrest syndrome. The four key components of PCAS were identified as (1) post-cardiac arrest brain. This glutamate-Ca2+ theory of excitotoxic neuronal cell death is widely accepted [24,25,26] According to this theory, the most important aspect of the pathogenesis of cerebral ischemia is the restriction of substrates and oxygen to the mitochondrial respiratory system and the induction of cellular ATP crisis. The most important aspect of the pathogenesis of cerebral ischemia is the restriction of substrates and oxygen to the mitochondrial respiratory system and the induction of cellular ATP crisis It is the loss of cellular energy and its repercussions that trigger acute or ing intracellular events: degradation of lipid membrane delayed neuronal cell death.
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