Neuronal mdr-1 gene expression after experimental focal hypoxia: A new obstacle for neuroprotection?

Lazarowski, Alberto; Caltana, Laura; Merelli, Amalia; Rubio, María Dolores Mesa; Ramos, Alberto Javier; Brusco, Alicia

doi:10.1016/j.jns.2007.03.004

Cited by 57 publications

(47 citation statements)

References 48 publications

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“…In accordance with the recently defined "neurovascular unit" for stroke by del Zoppo (2006), we believe that the critical role for ABCB1 gene induction should be extended to other brain cells, such as astrocytes and neurons, not only in hypoxic conditions (Lazarowski et al, 2007a) but also in epilepsy.…”

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confidence: 80%

P-Glycoprotein—a Clinical Target in Drug-Refractory Epilepsy?

2008

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supporting

confidence: 80%

P-Glycoprotein—a Clinical Target in Drug-Refractory Epilepsy?

2008

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“…Intrauterine death comprises more than half of all fetal deaths (7/12). P-gp expression in murine brains was increased following hypoxia-induced treatment (35). Thus hypoxia could have artificially increased the P-gp intensity in the fetal samples.…”

Section: Resultsmentioning

confidence: 99%

The ontogeny of P-glycoprotein in the developing human blood–brain barrier: implication for opioid toxicity in neonates

et al. 2015

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Background:Neonates have been shown to have a heightened sensitivity to the central depressive effects of opioids compared to older infants and adults. The limited development of P-glycoprotein (P-gp) may limit the ability of the neonate to efflux morphine from the brain back to the systemic circulation. The objective of the study was to determine the ontogeny of P-gp in the human brain. Methods: Postmortem cortex samples from gestational age (GA) 20-26 wk, GA 36-40 wk, postnatal age (PNA) 0-3 mo, PNA 3-6 mo, and adults were immunostained for P-gp. results: The intensity of P-gp staining in adults was significantly higher compared to at GA 20-26 wk (P < 0.05), GA 36-40 wk (P < 0.05), and PNA 0-3 mo (P < 0.05). P-gp intensity at GA 20-26 wk (P < 0.05), GA 36-40 wk (P < 0.05), and PNA 0-3 mo (P < 0.05) was significantly lower compared to at PNA 3-6 mo. conclusion: P-gp expression in the brain is limited at birth, increases with postnatal maturation, and reaches adult levels at ~3-6 mo of age. Given the immaturity of blood-brain barrier (BBB) P-gp after birth, morphine may concentrate in the brain. This provides mechanistic support to life threatening opioid toxicity seen with maternal codeine use during breastfeeding.

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“…In vivo, we have previously demonstrated that the intracerebral CoCl 2 injection induces the multidrug resistant gene (mdr-1) expression, both in neurons and astrocytes (Lazarowski et al 2007); however, the relationship between CoCl 2 brain injection and cellular alteration remains to be described.…”

Section: Introductionmentioning

confidence: 99%

Neuronal and Glial Alterations Due to Focal Cortical Hypoxia Induced by Direct Cobalt Chloride (CoCl2) Brain Injection

et al. 2009

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Ischemic brain injury is a dynamic process that involves oxidative stress, inflammation, and cell death, as well as activation of endogenous adaptive and regenerative mechanisms depending on activation of transcription factors such as hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF-1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2 injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2 microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2 microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24 h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342, TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin staining, and electron microscopy (EM) were performed. Immediately after 1 h post CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and cromathin condensation were observed by immunostaining and EM, respectively. Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin maximal reactivity were detected during 6-9 h. Ultrastructural alterations of morphology included edematous perinuclear cytoplasm, organelles and endoplasmic reticulum (RE) enlargement, mitochondrial swelling with increased matrix density, and deposits of electron-dense material. Neurons showed particular nuclear indentations. Astrocytes and oligodendrocytes presented alterations in both nuclei and RE with dilated lumen and altered mitochondrias, and all these ultrastructural changes became detectable at day 5. CoCl2 cortical injection mimics focal brain ischemia, inducing neuronal death and glial activation. This model brings the opportunity to develop focal ischemia in selected brain areas to study their functional consequences and potential pharmacological therapies for in vivo models of stroke.

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Neuronal mdr-1 gene expression after experimental focal hypoxia: A new obstacle for neuroprotection?

Cited by 57 publications

References 48 publications

P-Glycoprotein—a Clinical Target in Drug-Refractory Epilepsy?

P-Glycoprotein—a Clinical Target in Drug-Refractory Epilepsy?

The ontogeny of P-glycoprotein in the developing human blood–brain barrier: implication for opioid toxicity in neonates

Neuronal and Glial Alterations Due to Focal Cortical Hypoxia Induced by Direct Cobalt Chloride (CoCl2) Brain Injection

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