Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders

Papadopoulos, Vassilios; Lecanu, Laurent; Brown, Rachel C.; Han, Zeqiu; Yao, Zhixing

doi:10.1016/j.neuroscience.2005.05.063

Cited by 214 publications

(197 citation statements)

References 68 publications

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“…Previous investigations have indicated that the measurement of PBR density could be of widespread applicability in the quantification of neural tissue damage in the central nervous system as this astrocytes and microglia receptor is a known indicator of cell stress in many conditions. 32,33 Moreover, given that different areas in the brain are affected upon exposure to organophosphate (see Introduction); we sought to analyze and compare the brains of the naïve versus the two treated groups. Using a radioactive affinity assay, we observed a significantly lower concentration of PBR in the brain of the naïve animals (see Figure 5; 132 ± 13 fmol/ mg; n ¼ 5) versus the two groups that were exposed to PO, indicative of the stress caused by this challenge.…”

Section: Effects Of Glutamate Scavengers On the Central Nervous Systemmentioning

confidence: 99%

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Ruban

Jona

Teichberg

2013

J Cereb Blood Flow Metab

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Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.

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Section: Effects Of Glutamate Scavengers On the Central Nervous Systemmentioning

confidence: 99%

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Ruban

Jona

Teichberg

2013

J Cereb Blood Flow Metab

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“…S3). The TSPO is proposed to translocate cholesterol from the outer to the inner mitochondrial membrane for downstream synthesis of all steroids in the peripheral tissues, but in the CNS the end products are primarily neurosteroids (24)(25)(26). Earlier, TSPO ligands were shown to have antinociceptive and antiinflammatory effects (27,28 (29)(30)(31).…”

Section: Inhibitors Of Seh Have Cox2-independent Antihyperalgesic Effmentioning

confidence: 99%

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

Inceoglu¹,

Jinks

Ulu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

163

214

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During inflammation, a large amount of arachidonic acid (AA) is released into the cellular milieu and cyclooxygenase enzymes convert this AA to prostaglandins that in turn sensitize pain pathways. However, AA is also converted to natural epoxyeicosatrienoic acids (EETs) by cytochrome P450 enzymes. EET levels are typically regulated by soluble epoxide hydrolase (sEH), the major enzyme degrading EETs. Here we demonstrate that EETs or inhibition of sEH lead to antihyperalgesia by at least 2 spinal mechanisms, first by repressing the induction of the COX2 gene and second by rapidly up-regulating an acute neurosteroid-producing gene, StARD1, which requires the synchronized presence of elevated cAMP and EET levels. The analgesic activities of neurosteroids are well known; however, here we describe a clear course toward augmenting the levels of these molecules. Redirecting the flow of pronociceptive intracellular cAMP toward up-regulation of StARD1 mRNA by concomitantly elevating EETs is a novel path to accomplish pain relief in both inflammatory and neuropathic pain states.cAMP ͉ inflammatory pain ͉ steroidogenesis

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“…Steroids (glucocorticoids and mineralocorticoids) are involved in numerous physiological processes, including immunomodulation [21]. They are generated from cholesterol in the adrenal glands or the gonads, but some can also be formed in the CNS (neurosteroids) [22,23].…”

Section: Introductionmentioning

confidence: 99%

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

Gachet

Rhyn

Bosch

et al. 2015

Journal of Chromatography B

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Peripheral-type benzodiazepine receptor in neurosteroid biosynthesis, neuropathology and neurological disorders

Cited by 214 publications

References 68 publications

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Blood Glutamate Scavenging as a Novel Neuroprotective Treatment for Paraoxon Intoxication

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

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