CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

Lazarowski, Alberto; Fabiana, Lubieniecki; Sandra, Camarero; Cuccia, Vicente; Analía, Taratuto

doi:10.14800/rci.53

Cited by 6 publications

(3 citation statements)

References 56 publications

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“…Similar results were also described in a pediatric case with focal cortical dysplasia, 46 in another case with transmantle cortical dysplasia, 47 and some patients with epilepsy due to brain tumors. 48 , 49 Consistent with these clinical findings, neuronal expression of P‐gp was also observed in different experimental models of seizures 29 , 50 and brain hypoxia, 51 where administration of nimodipine restored PHT PK in the hippocampus, with complete recovery of protection against induced seizures. 52 …”

Section: Abc‐t In the Central Mechanism Of Drug‐resistance Epilepsy: ...supporting

confidence: 65%

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

2021

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The multidrug-resistance (MDR) phenotype is typically observed in patients with refractory epilepsy (RE) whose seizures are not controlled despite receiving several combinations of more than two antiseizure medications (ASMs) directed against different ion channels or neurotransmitter receptors. Since the use of bromide in 1860, more than 20 ASMs have been developed; however, historically ~30% of cases of RE with MDR phenotype remains unchanged. Irrespective of metabolic biotransformation, the biodistribution of ASMs and their metabolites depends on the functional expression of some ATP-binding cassette transporters (ABC-t) in different organs, such as the blood-brain barrier (BBB), bowel, liver, and kidney, among others. ABC-t, such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP-1), and breast cancer-resistance protein (BCRP), are mainly expressed in excretory organs and play a critical role in the pharmacokinetics (PK) of all drugs. The transporter hypothesis can explain pharmacoresistance to a broad spectrum of ASMs, even when administered simultaneously. Since ABC-t expression can be induced by hypoxia, inflammation, or seizures, a high frequency of uncontrolled seizures increases the risk of RE.These stimuli can induce ABC-t expression in excretory organs and in previously non-expressing (electrically responsive) cells, such as neurons or cardiomyocytes. In this regard, an alternative mechanism to the classical pumping function of P-gp indicates that P-gp activity can also produce a significant reduction in resting membrane potential (ΔΨ0 = −60 to −10 mV). P-gp expression in neurons and cardiomyocytes can produce membrane depolarization and participate in epileptogenesis, heart failure, and sudden unexpected death in epilepsy. On this basis, ABC-t play a peripheral role in controlling the PK of ASMs and their access to the brain and act at a central level, favoring neuronal depolarization by mechanisms independent of ion channels or neurotransmitters that current ASMs cannot control.

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Section: Abc‐t In the Central Mechanism Of Drug‐resistance Epilepsy: ...supporting

confidence: 65%

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

2021

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“…Heterogeneous distributions for these markers were detected with differential immunostaining pattern, showing high immunoreactivity in SEGA cells far of vessels, and low or negative expression in SEGA cells near the vessels. This particular expression pattern of both ABC-transporters, and CD34 antigen could identify different stem-cell subset in SEGA [69].…”

Section: P-gp As Stem Cell Marker Of Brain Malformation/tumor Refractmentioning

confidence: 87%

“…In all of them, overexpression of ABC-transporters as P-glycoprotein, MRPs and BCRP were described [10,24,45,69,73].…”

Section: P-gp As Stem Cell Marker Of Brain Malformation/tumor Refractmentioning

confidence: 99%

The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment

Lazarowski¹,

Czornyj²,

Rocha³

2015

ADMET DMPK

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Pharmacogenetics in Epilepsy and Refractory Epilepsy

Czornyj,

Auzmendi,

Lazarowski

2023

Pharmacoresistance in Epilepsy

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CD34 stem-cell marker and multidrug resistance proteins P-gp and BCRP in SEGA

Cited by 6 publications

References 56 publications

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

Transporter hypothesis in pharmacoresistant epilepsies. Is it at the central or peripheral level?

The complexity of roles of P-glycoprotein in refractory epilepsy: Pharmacoresistance, epileptogenesis, SUDEP and relapsing marker after surgical treatment

Pharmacogenetics in Epilepsy and Refractory Epilepsy

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