Cognitive impairment in sepsis survivors from cecal ligation and perforation*

Barichello, Tatiana; Martins, Márcio Rodrigo; Reinke, Adalisa; Feier, Gustavo; Ritter, Cristiane; Quevedo, Joao L De

doi:10.1097/01.ccm.0000150741.12906.bd

Cited by 121 publications

(73 citation statements)

References 9 publications

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“…The animals were subjected to CLP as previously described (19)(20)(21)(22). Briefly, rats were anesthetized with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), given intraperitoneally.…”

Section: Cecal Ligation and Perforation Surgerymentioning

confidence: 99%

“…Shimizu et al (23) demonstrated that 24 h after CLP animals presented learning impairment in passive avoidance retention. Moreover, we recently reported that CLP-induced sepsis survivors presented learning, aversive and spatial memory impairment when submitted to behavioral tasks 10 days after CLP (21) and learning and aversive memory impairment lasting up to 30 days after CPL (22). Thus, CLP seems to be a good model for the study of cognitive and emotional alterations as late manifestation of sepsis.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, murine models of cecal ligation and perforation (CLP) are clinically relevant since they induce a polymicrobial sepsis that mimics human sepsis (19)(20)(21)(22). The CLP model has contributed to the elucidation of the pathogenesis and to the determination of new therapies in sepsis (19,20).…”

Section: Introductionmentioning

confidence: 99%

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Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

Barichello

Martins

Reinke

et al. 2007

Braz J Med Biol Res

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Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short-and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short-and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxietylike behavior.

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Section: Cecal Ligation and Perforation Surgerymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

Barichello

Martins

Reinke

et al. 2007

Braz J Med Biol Res

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“…(43,44) Acute encephalopathy has demonstrated in animal models of polymicrobial sepsis, and human sepsis survivors present cognitive impairment that could be a secondary effect of CNS damage. (26) In addition, survivors from critical care units, including sepsis patients, may show persistent brain-related morbidity, including neurocognitive deficits and development of psychiatric disorders. (45)(46)(47)(48)(49) In the present study, we demonstrate that citrate synthase activity is inhibited in the prefrontal cortex and cerebral cortex of adult rats after sepsis induced by CLP.…”

Section: Discussionmentioning

confidence: 99%

“…All animals showed signs of encephalopathy at 6 h after sepsis (lethargy, mild ataxia, lack of spontaneous movement, and loss of righting reflex) and gradually returned to their normal waking status 24-36 h after CLP. (26) To minimize the possibility of animals not developing sepsis, the CLP procedure was always performed by the same investigators. In addition, all animals were observed after CLP to determine signs of infection (pyloerection, lethargy, tachypnoea and weight loss), and the number of animals that survived is in accordance with our previous reports.…”

Section: Cecal Ligation and Perforation Surgerymentioning

confidence: 99%

Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse

Scaini¹,

Rochi²,

Benedet³

et al. 2011

Rev. bras. ter. intensiva

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Objective: An extensive body of evidence from experimental studies indicates that sepsis is associated with increased reactive oxygen species production, depletion of antioxidants, and accumulation of markers of oxidative stress. Moreover, mitochondrial dysfunction has been implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). Citrate synthase is an enzyme localized in the mitochondrial matrix and an important component of the Krebs cycle; consequently, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase activity in the brains of rats submitted to a cecal ligation puncture model of sepsis.Methods: At several times points (3, 6, 12, 24 and 48 hours) after the cecal ligation puncture operation, six rats were killed by decapitation. Their brains were removed, and the hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used

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Animal models of neuroinflammation secondary to acute insults originated outside the brain

Hamasaki

Machado

Silva

2017

J of Neuroscience Research

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The term "neuroinflammation" has been widely used to describe a series of acute or chronic conditions that cause inflammation in the central nervous system (CNS). Neurological damage can be a consequence of direct local injury or, secondary, of systemic or even distant inflammatory processes. In this respect, animal models have been developed to better understand the pathophysiology and, possibly, to evaluate more effective methods of treatment for these disorders. Animal models that promote alterations in blood-brain barrier permeability-the activation of microglia or astrocytes, modifications in neuropeptide expression, oxidative stress, increased apoptosis, release of inflammatory mediators, leukocyte infiltration, and brain edema-are likely to involve neuroinflammation and therefore can serve as useful models for human inflammatory CNS injury. This review describes the major animal models of neuroinflammation triggered by systemic or distant inflammatory processes. We will focus on animal models of acute neurologic damage; experimental models that lead to chronic neuroinflammation will not be addressed here.

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Cognitive impairment in sepsis survivors from cecal ligation and perforation*

Abstract: Our data provide the first experimental demonstration that survivors from CLP show learning and memory impairment after complete physical recovery from sepsis.

Cited by 121 publications

References 9 publications

Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

Inibição da atividade da citrato sintase cerebral em um modelo animal de sepse

Animal models of neuroinflammation secondary to acute insults originated outside the brain

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