ReferenceID 2592

The effect of parthenolide on methamphetamine-induced blood-brain barrier and astrocyte alterations

Eur J Clin Invest

Background: Methamphetamine abuse is a worldwide concern with long-term health complications. Its impact on neurons has been extensively investigated, and it is currently known that glial cells, including astrocytes, are

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Reference Id
2592
Evidence Id
19182
Core Evidence Id
19182
Source Reference Id
5175
Herb2 Reference Id
HBREF005972
Subject Paper Key
HBIN038876_34694635
Pubmed Id
34694635
Doi
10.1111/eci.13694
Paper Title
The effect of parthenolide on methamphetamine-induced blood-brain barrier and astrocyte alterations
Paper Abstract
Background: Methamphetamine abuse is a worldwide concern with long-term health complications. Its impact on neurons has been extensively investigated, and it is currently known that glial cells, including astrocytes, are involved in drug-induced outcomes. Importantly, METH also causes blood-brain barrier (BBB) disruption and astrocytes are critical for BBB (dys)function. Therefore, we aimed to clarify the involvement of neuroinflammation mediated by astrocytes in BBB permeability and brain oedema induced by METH. Further, we aimed to identify a new approach to counteract METH effects. Methods: Mice were administered with a METH binge regimen (4 × 10 mg/kg) alone or in combination with parthenolide (PTL; 4 × 1 mg/kg), and hippocampi were analysed. For in vitro studies, mouse primary cultures of astrocytes were exposed to 250 µM METH, alone or co-treated with 10 µM PTL. Results: We observed a neuroinflammatory response characterized by astrocytic morphological changes and increased TNF-α, iNOS and ICAM-1 protein levels (213.62%, 205.76% and 191.47% of control, respectively). Additionally, brain oedema and BBB disruption were identified by increased water content (81.30% of tissue weight) and albumin (224.40% of control) in the hippocampal tissue, as well as a significant decrease in vessel coverage by astrocytes after METH exposure. Regarding astrocyte cultures, we further identified TNF-α as a key player in METH-induced cell swelling. Importantly, PTL (present in feverfew plant) prevented both animal and in vitro effects induced by METH. Conclusions: We provided important insights on brain dysfunction induced by METH, and we also suggest a new approach to counteract such negative effects.
Journal
Eur J Clin Invest
Publish Year
2021
Experiment Subject
mouse; astrocyte cultures; mouse primary cultures
Experiment Type
Animal & Cell Experiment
Phenotype Related
Brain Oedema; Brain Dysfunction
Paper Title Cn
Paper Title En
The effect of parthenolide on methamphetamine-induced blood-brain barrier and astrocyte alterations
Bilingual Status
semi_complete