Sepsis Associated Encephalopathy

Chaudhry, Neera; Duggal, Ashish

doi:10.1155/2014/762320

Cited by 177 publications

(188 citation statements)

References 123 publications

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“…Recent studies have illustrated the pathophysiology of SAE and encephalitis involving BBB dysfunction, neuroinflammation, and apoptosis [16,23]. In this study, we observed that the inhibition of Omi/HtrA2 by UCF-101 substantially improves the sepsis-induced loss of BBB integrity, as demonstrated by improvements in Evans blue extravasation and endothelial tight junction protein expression.…”

Section: Cellular Physiology and Biochemistry Cellular Physiology Andsupporting

confidence: 49%

“…It may involve brain microvascular endothelial cell dysfunction, destruction of the BBB, cerebral local inflammatory cell infiltration, inflammation medium, reduced cerebral perfusion, cerebral microvascular adjustment disorder, astrocyte and neuron dysfunction, neurotransmitter disorders, mitochondrial dysfunction, apoptosis, oxidative stress, calcium disorders, and so on [1,13,15]. Compelling evidence indicates that oxidative stress, mitochondrial dysfunction, and apoptosis play critical roles in the pathogenesis of SAE [16]. Accordingly, oxidative stress may promote the pathogenesis of SAE by enhancing the expression of proinflammatory cytokines, promoting apoptosis, and/ or interfering with BBB function.…”

Section: Discussionmentioning

confidence: 99%

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Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Wang

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: the pathogenesis of sepsis-associated encephalopathy (SAE) is multifactorial, involving neurotransmitter alterations, inflammatory cytokines, oxidative damage, mitochondrial dysfunction, apoptosis, and other factors. Mitochondria are major producers of reactive oxygen species, resulting in cellular injury. Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent cell death; it is translocated from mitochondria to the cytosol after an apoptotic insult. We previously found that UCF-101, a specific inhibitor of Omi/HtrA2, has neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats. In this study, the mechanisms and molecular pathways underlying these effects were investigated. Methods: Male Sprague–Dawley rats were subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy and were administered vehicle or UCF-101 (10 µmol/kg). The hippocampus was isolated for subsequent analysis. Omi/HtrA2 expression in the mitochondria or cytosol was evaluated by immunofluorescence or western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was utilized to evaluate levels of apoptosis, and western blotting was used to evaluate apoptosis-related proteins, such as cleaved caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP). Tight junction expression was assessed by immunofluorescence and western blotting. Mitochondrial function, inflammatory cytokines, and oxidative stress were also assayed. In addition, a wet/dry method was used to evaluate brain edema and Evans blue extravasation was used to evaluate blood–brain barrier (BBB) integrity. Results: After CLP treatment, the hippocampus exhibited a mild increase in Omi/HtrA2 expression; cytosolic Omi/HtrA2 expression increased significantly, whereas mitochondrial Omi/HtrA2 expression was reduced, indicating that CLP-induced oxidative stress resulted in the translocation of Omi/HtrA2 from mitochondria to the cytosol. Hippocampal cleaved caspase-3, caspase-9, and PARP levels were significantly higher in animals treated with CLP than in sham-operated animals, while XIAP expression was lower. Treatment with UCF-101 prevented the mobilization of Omi/HtrA2 from mitochondria to the cytosol, attenuated XIAP degradation, and decreased cleaved caspase-3, caspase-9, and PARP expression as well as apoptosis. UCF-101 also reversed the decreased mitochondrial complex I, II, and III respiration and the reduced ATP caused by CLP. In addition, UCF-101 treatment resulted in a significant improvement in BBB integrity, as demonstrated by increased occludin, claudin-5, and zonula occludens 1 levels and reduced Evans blue extravasation. No significant effects of UCF-101 on brain edema were found. Inflammatory cytokines and oxidative stress were significantly higher in the CLP-treated group than in the sham-operated group. However, the inhibition of Omi/HtrA2 by UCF-101 significantly alleviated these responses. Conclusion: Our data indicated that Omi/ HtrA2 regulates a ...

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Section: Cellular Physiology and Biochemistry Cellular Physiology Andsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Wang

Yao

et al. 2018

Cell Physiol Biochem

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“…Hence, it required urgent drainage even in the presence of neuropsychiatric symptoms. 2 Wilson's disease rarely presents with acute psychosis. 3 Here the child presented with acute psychosis and was posted for a semi-emergent surgery before resolution of symptoms.…”

Section: Discussionmentioning

confidence: 99%

Anaesthetic management in Wilson's disease with severe neuropsychiatric manifestations

Nanjangud

Prasad²

2017

Sri Lankan J Anaesthesiol

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A 15 year-old girl presented with acute psychosis, seizures and right shoulder dislocation with an overlying abscess. The symptomatology was diagnosed to be due to Wilson's disease. The anaesthetic management and postoperative analgesia was a challenging task in presence of hepatic and acute neurological dysfunction as well as difficulty in pain assessment. There are only a few reported cases of anaesthetic management in patients with Wilson's disease with severe neuropsychiatric symptoms. This case portrays the safe use of both general and regional anaesthesia in such a patient. Keywords:Wilson's disease; neuro-psychiatric symptoms; anaesthesia; interscalene block Case Report A 15yr old, 30kg girl presented with progressive slurring of speech, gait disturbance, insomnia and altered behaviour over a period of 20 days. She was admitted to a psychiatric hospital and started on risperidone and carbamazepine. A week later, she developed tightness of all four limbs and focal seizures. Quetiapine and thioridazine were added for better symptom control. She was then transferred to Kasturba Hospital, Manipal. There was no history of trauma, chronic fever or drug abuse. Perinatal period and development were within normal limits. There were no psychiatric/ genetic disorders or untimely deaths in her family. On admission, child had resting tremors, choreoathetoid movements, hypertonia of all four limbs and recurrent right sided focal seizures. Later, child was noted to have fluctuating consciousness, inattention and inappropriate laughter and crying. Examination revealed a swollen and dislocated right shoulder. A provisional diagnosis of encephalopathy was made and further evaluation was performed. Biochemical tests revealed increased serum copper (209mcg/dL) and urine copper levels (373mcg/24h) and mildly elevated liver enzymes in serum (Aspartate Transaminase-75 IU/L, Alanine Transaminase-109 IU/L, Alkaline phosphatase-87 U/L). Computed tomographic scan of brain and cerebro-spinal fluid studies were normal. Toxicology and metabolic screening tests ruled out toxins and inborn errors of metabolism. Steroids and penicillamine were started with a presumptive diagnosis of Wilson's disease.Trihexiphenidyl, quetiapine and levetiracetam were used to control her symptoms. A week after therapy, the swelling over the right shoulder was diagnosed to be a developing abscess. Orthopaedic surgeon scheduled her for closed/open reduction of the dislocation with drainage of abscess. Written informed consent was obtained from the parents for surgery and anaesthesia, after explaining the risk of perioperative adverse events.Our initial plan was to provide an interscalene block. However, due to the fluctuating consciousness and recurrent choreo-athetoid movements, we proceeded with general anaesthesia. Electrocardiogram, non-invasive blood pressure and pulse oximetry was established and a 20G venous cannula secured and anaesthesia induced with fentanyl 60mcg and propofol 40mg. Atracurium 15mg was used to facilitate tracheal intubation with 6....

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“…Lebih dari itu, ensefalopati sepsis dikaitkan dengan prognosis yang buruk. 6,7 Salah satu biomarker yang sampai sekarang masih diteliti adalah NSE. Neuron-specific enolase adalah enzim glikolitik sitoplasma yang ditemukan pada sel neuron dan sel neuroendokrin.…”

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Hubungan Kadar Neuron-Specific Enolase Serum dengan Mortalitas pada Sepsis Neonatorum

Hartanto

Masloman

Rompis

et al. 2016

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Latar belakang. Sepsis neonatorum menyebabkan respons inflamasi berlebih sehingga terjadi kerusakan sawar darah otak, disfungsi serebrovaskular dan oksigenasi, gangguan neurotransmiter, degenerasi sel neuron, edema serebral yang berakhir pada kematian sel. Penelitian sebelumnya mendapatkan peningkatan kadar NSE serum pada pasien anak dengan sepsis berat dan syok septik. Tujuan. Mengetahui hubungan kadar NSE serum dengan mortalitas pada sepsis neonatorum. Metode. Digunakan metode analitik observasional kohort prospektif dari bulan Agustus 2015 sampai November 2015. Sampel diambil secara konsekutif dan didapatkan 42 bayi dengan sepsis neonatorum. Analisis statistik diuji dengan regresi logistik dan korelasi Pearson. Orang tua atau wali diminta menandatangani informed consent. Penelitian ini dilaksanakan dibawah persetujuan komite etik. Hasil. Terdapat hubungan antara kadar NSE serum dengan mortalitas (koefisien korelasi r pb =0,738 dengan nilai p<0,001). Cutt-off point kadar NSE serum yaitu 21,9 µg/L dengan sensitivitas 91,3% dan spesifisitas 94,7% dalam menentukan mortalitas pada sepsis neonatorum. Kesimpulan. Semakin tinggi kadar NSE serum maka semakin besar peluang bayi dengan sepsis akan meninggal. Sari Pediatri 2016; 17(6):450-4. Kata kunci: neuron-specific enolase, mortalitas, sepsis neonatorumBackground. Neonatal sepsis causes excessive inflammatory responses, which in turn causes damage to the blood brain barrier, cerebrovascular dysfunction and oxygenation, neurotransmitter disorders, neuron degeneration, and cerebral edema, that ended in the cell death. Previous studies showed elevated levels of serum NSE in pediatric patients with severe sepsis and septic shock. Objective. To determine the relationship of serum NSE levels with mortality in neonatal sepsis. Method. We conducted an observational analytical study with prospective cohort approach from August 2015 until November 2015. Samples were taken consecutively. Forty-two infants with neonatal sepsis were enrolled into the study. The relationship between serum NSE levels with mortality was tested with logistic regression analysis and Pearson correlation test. Informed consent was obtained from parents or guardians. This study was approved by ethical comittee. Results. There is a significant correlation between serum NSE levels with mortality in neonatal sepsis (correlation coefficient r pb = 0.738 with p <0.001). Cut-off point of serum NSE levels to determine risk of mortality is 21.9 µg/L with a sensitivity of 91.3% and specificity of 94.7%. Conclusion. This study shows that the higher levels of serum NSE, the greater chances of newborns with sepsis will die. Sari Pediatri 2016; 17(6):450-4.

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Sepsis Associated Encephalopathy

Cited by 177 publications

References 123 publications

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Omi/HtrA2 Regulates a Mitochondria-Dependent Apoptotic Pathway in a Murine Model of Septic Encephalopathy

Anaesthetic management in Wilson's disease with severe neuropsychiatric manifestations

Hubungan Kadar Neuron-Specific Enolase Serum dengan Mortalitas pada Sepsis Neonatorum

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