Central nervous system stimulants promote nerve cell death under continuous hypoxia.


Journal

Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329

Informations de publication

Date de publication:
Sep 2022
Historique:
received: 26 04 2022
accepted: 02 06 2022
pubmed: 24 6 2022
medline: 17 8 2022
entrez: 23 6 2022
Statut: ppublish

Résumé

Intake of central nervous system (CNS) stimulants causes hypoxia and brain edema, which results in nerve cell death. However, no study has yet investigated the direct and continuous effects on nerve cells of CNS stimulants under hypoxia. Thus, based on autopsy cases, the effects of CNS stimulant drugs on the CNS were examined. The pathological changes in cultured nerve cells when various CNS stimulants were added under a hypoxic condition were also investigated. Five groups (Group A, stimulants; Group B, stimulants with psychiatric drugs; Group C, caffeine; Group D, psychiatric drugs; and Group E, no drugs) according to the detected drugs in autopsy cases were compared, and brain edema was evaluated using morphological findings. Furthermore, the number of dead cultured nerve cells was counted after the addition of drugs (4-aminopyridine (4-AP), caffeine, and ephedrine) under hypoxia (3% O2). Staining with anti-receptor-interacting protein 3 (RIP3) and other associated stains was also performed to investigate the neuronal changes in the brain. Group A showed significantly more brain edema than the other groups. In the culture experiments, the ratio of nerve cell death after the addition of 4-AP was the highest in the hypoxic condition. Groups with stimulants detected were stained more strongly by RIP3 immunostaining than by other staining. Addition of stimulants to cultured nerve cells in a persistent hypoxic condition led to severe cytotoxicity and nerve cell death. These findings suggest that necroptosis is involved in nerve cell death due to the addition of CNS stimulants in the hypoxic condition.

Identifiants

pubmed: 35737220
doi: 10.1007/s13577-022-00734-0
pii: 10.1007/s13577-022-00734-0
doi:

Substances chimiques

Central Nervous System Stimulants 0
Caffeine 3G6A5W338E

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1391-1407

Informations de copyright

© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.

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Auteurs

Kei Ikeda-Murakami (K)

Department of Legal Medicine, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan. d19ma001@st.osaka-cu.ac.jp.

Tomoya Ikeda (T)

Department of Legal Medicine, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.
Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, Department of Legal Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.

Miho Watanabe (M)

Laboratory of Clinical Regenerative Medicine, Department of Neurosurgery, Faculty of Medicine, Health and Medical Science Innovation Laboratory 403, University of Tsukuba, Tsukuba City, Ibaraki, 305-8575, Japan.

Naoto Tani (N)

Department of Legal Medicine, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.
Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, Department of Legal Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.

Takaki Ishikawa (T)

Department of Legal Medicine, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.
Forensic Autopsy Section, Medico-Legal Consultation and Postmortem Investigation Support Center, Department of Legal Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno, Osaka, 545-8585, Japan.

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