Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia

Capani, Francisco; Saraceno, Gustavo Ezequiel; Botti, Valeria; Aon-Bertolino, Laura; Oliveira, Diêgo Madureira de; Barreto, George E.; Galeano, Pablo; Giraldez-Alvarez, Lisandro Diego; Coirini, Héctor

doi:10.1016/j.expneurol.2009.06.007

Cited by 42 publications

(97 citation statements)

References 59 publications

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“…No study to date has assessed the effect of TH on synaptic dysfunction after TBI, though TH has been shown to preserve certain synaptic properties. In particular, it decreases misfolding and aggregation of proteins in postsynaptic densities of hippocampal neurons after global cerebral ischemia [Capani et al, 2009;Dong et al, 2001]. Hypothermic conditions have also been reported to attenuate the constitutive release of ␣ -synuclein from the presynaptic terminal [Lee et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Su¹,

Bell²,

Wisniewski

et al. 2010

Dev Neurosci

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α-Synuclein is one of the most abundant proteins in presynaptic terminals. Normal expression of α-synuclein is essential for neuronal survival and it prevents the initiation of apoptosis in neurons through covalent cross-linking of cytochrome c released from mitochondria. Exocytosis of α-synuclein occurs with neuronal mitochondrial dysfunction, making its detection in cerebrospinal fluid (CSF) of children after severe traumatic brain injury (TBI) a potentially important marker of injury. Experimental therapeutic hypothermia (TH) improves mitochondrial function and attenuates cell death, and therefore may also affect CSF α-synuclein concentrations. We assessed α-synuclein levels in CSF of 47 infants and children with severe TBI using a commercial ELISA for detection of monomeric protein. 23 patients were randomized to TH based on published protocols where cooling (32–33°C) was initiated within 6–24 h, maintained for 48 h, and then followed by slow rewarming. CSF samples were obtained continuously via an intraventricular catheter for 6 days after TBI. Control CSF (n = 9) was sampled from children receiving lumbar puncture for CSF analysis of infection that was proven negative. Associations of initial Glasgow Coma Scale (GCS) score, age, gender, treatment, mechanism of injury and Glasgow Outcome Scale (GOS) score with CSF α-synuclein were compared by multivariate regression analysis. CSF α-synuclein levels were elevated in TBI patients compared to controls (p = 0.0093), with a temporal profile showing an early, approximately 5-fold increase on days 1–3 followed by a delayed, >10-fold increase on days 4–6 versus control. α-Synuclein levels were higher in patients treated with normothermia versus hypothermia (p = 0.0033), in patients aged <4 years versus ≧4 years (p < 0.0001), in females versus males (p = 0.0007), in nonaccidental TBI versus accidental TBI victims (p = 0.0003), and in patients with global versus focal injury on computed tomography of the brain (p = 0.046). Comparisons of CSF α-synuclein levels with initial GCS and GOS scores were not statistically significant. Further studies are needed to evaluate the conformational status of α-synuclein in CSF, and whether TH affects α-synuclein aggregation.

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Section: Introductionmentioning

confidence: 99%

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Su¹,

Bell²,

Wisniewski

et al. 2010

Dev Neurosci

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“…As a consequence, brain hypoxia along with ischemia and the reduced cerebral blood flow (CBF) might lead to perinatal HIE [2, 3]. The most vulnerable areas of the immature brain are: the cornu ammonis (CA1, CA3 and CA4) regions of the hippocampus, the cerebellum, layers III, V and VI of the neocortex and the neostriatum [4]. At cellular level different pathological cascades can directly contribute to long-term apoptosis in distal neuronal structures: oxidative stress, peroxynitrite-induced neurotoxicity, lipid peroxidation, mitochondrial and DNA damage [5-7].…”

Section: Introductionmentioning

confidence: 99%

Use of estetrol with other steroids for attenuation of neonatal hypoxic-Ischemic brain injury: to combine or not to combine?

et al. 2016

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Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated. The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4.

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“…GFAP is an intermediate filament protein specifically expressed in astroglia, the dominant and functionally most dynamic glial cell type [51,52]. In addition, we also analyzed the levels of HSP70 [46,47] and poly-ubiquitinylation of proteins [53][54][55] as markers for neuronal and protein damage, respectively (Fig. 5d, e).…”

Section: The Importance and Effects Of Trx1 And Grx2 In A Cellular Momentioning

confidence: 99%

Thioredoxin 1 and glutaredoxin 2 contribute to maintain the phenotype and integrity of neurons following perinatal asphyxia

Romero

Hanschmann

Gellert

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia

Cited by 42 publications

References 59 publications

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

α-Synuclein Levels Are Elevated in Cerebrospinal Fluid following Traumatic Brain Injury in Infants and Children: The Effect of Therapeutic Hypothermia

Use of estetrol with other steroids for attenuation of neonatal hypoxic-Ischemic brain injury: to combine or not to combine?

Thioredoxin 1 and glutaredoxin 2 contribute to maintain the phenotype and integrity of neurons following perinatal asphyxia

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