Estimated Cerebral Perfusion Pressure and Intracranial Pressure in Septic Patients

Crippa, Ilaria Alice; Vincent, Jean‐Louis; Cavicchi, Federica Zama; Pozzebon, Selene; Gaspard, Nicolas; Maenhout, Christelle; Créteur, Jacques; Taccone, Fabio Silvio

doi:10.1007/s12028-023-01783-5

Cited by 1 publication

(2 citation statements)

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“…The mechanisms driving sepsis encephalopathy are thought to involve an impaired microvascular blood brain barrier, hypo-and hyper-coagulation, and reduced perfusion, in response to systemic inflammatory cytokines (1,4,(9)(10)(11)(12)(13). Post-mortem analysis of septic shock decedents shows a pathology consistent with severe brain endotheliopathy, including edema, hemorrhage, microthrombi, and ischemia that is associated with higher IL-6 expression, microglia activation and neuronal apoptosis (26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…Patients admitted at the ICU due to shock are at high risk of developing multiorgan failure, in large part due to a dysregulated inflammatory reaction that involves large concentrations of circulating cytokines, a condition usually known as a 'cytokine storm' (8). The mechanisms driving encephalopathy are thought to involve an impaired microvascular blood-brain barrier, coagulopathy, and reduced perfusion, in response to systemic inflammatory cytokines (1,4,(9)(10)(11)(12)(13). Thus, targeting the brain microvasculature response to shock is a promising avenue to prevent or limit SAE.…”

Section: Introductionmentioning

confidence: 99%

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A transient brain endothelial translatome response to endotoxin is associated with mild cognitive changes post-shock in young mice

Lu,

John Portela,

Martino

et al. 2024

Preprint

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Sepsis-associated encephalopathy (SAE) is a common manifestation in septic patients that is associated with increased risk of long-term cognitive impairment. SAE is driven, at least in part, by brain endothelial dysfunction in response to systemic cytokine signaling. However, the mechanisms driving SAE and its consequences remain largely unknown. Here, we performed translating ribosome affinity purification (TRAP) and RNA-sequencing (TRAP-seq) from the brain endothelium to determine the transcriptional changes after an acute endotoxemic (LPS) challenge. We found that LPS induces a strong acute transcriptional response in the brain endothelium that partially correlates with the whole brain transcriptional response and suggested an endothelial-specific hypoxia response. Consistent with a critical role for the IL-6 pathway, loss of the main regulator of this pathway, SOCS3, leads to a broadening of the population of genes responsive to LPS, suggesting that an overactivation of the IL-6/JAK/STAT3 pathway leads to an increased transcriptional response that could explain our prior findings of severe brain injury in these mice. To identify any potential sequelae of this acute response, we performed brain TRAP-seq following a battery of behavioral tests in mice after apparent recovery. We found that the transcriptional response returns to baseline within days post-challenge. Despite the transient nature of the response, we observed that mice that recovered from the endotoxemic shock showed mild, sex-dependent cognitive impairment, suggesting that the acute brain injury led to sustained, non-transcriptional effects. A better understanding of the transcriptional and non-transcriptional changes in response to shock is needed in order to prevent and/or revert the devastating consequences of septic shock.

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