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Molecular pathology of brain matrix metalloproteases, claudin5, and aquaporins in forensic autopsy cases with special regard to methamphetamine intoxication

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Abstract

Methamphetamine (METH) is a highly addictive drug of abuse and toxic to the brain. Recent studies indicated that besides direct damage to dopamine and 5-HT terminals, neurotoxicity of METH may also result from its ability to modify the structure of blood-brain barrier (BBB). The present study investigated the postmortem brain mRNA and immunohistochemical expressions of matrix metalloproteases (MMPs), claudin5 (CLDN5), and aquaporins (AQPs) in forensic autopsy cases of carbon monoxide (n = 14), METH (n = 21), and phenobarbital (n = 17) intoxication, compared with mechanical asphyxia (n = 15), brain injury (n = 11), non-brain injury (n = 21), and sharp instrument injury (n = 15) cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of AQP4 and MMP9, lower expression of CLDN5 in METH intoxication cases and lower expression of MMP2 in phenobarbital intoxication cases. Immunostaining results showed substantial interindividual variations in each group, showing no evident differences in distribution or intensity among all the causes of death. These findings suggest that METH may increase BBB permeability by altering CLDN5 and MMP9, and the self-protective system maybe activated to eliminate accumulating water from the extracellular space of the brain by up-regulating AQP4. Systematic analysis of gene expressions using real-time PCR may be a useful procedure in forensic death investigation.

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Acknowledgments

All practical work was performed at the Department of Legal Medicine Osaka City University.

This work was partially funded by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology, Japan (grant nos. 21790612 and 22590642).

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Authors and Affiliations

  1. Department of Forensic Medicine, Southern Medical University, No. 1838, Guangzhou, 510515, Guangdong Province, People’s Republic of China

    Qi Wang

  2. Department of Legal Medicine, Osaka City University Medical School, Osaka, Japan

    Qi Wang, Takaki Ishikawa, Tomomi Michiue & Hitoshi Maeda

  3. Division of Legal Medicine, Faculty of Medicine, Tottori University, Tottori, Japan

    Takaki Ishikawa

  4. Department of Forensic Pathology, China Medical University School of Forensic Medicine, Shenyang, China

    Bao-Li Zhu & Da-Wei Guan

Authors
  1. Qi Wang
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  2. Takaki Ishikawa
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  3. Tomomi Michiue
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  4. Bao-Li Zhu
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  5. Da-Wei Guan
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  6. Hitoshi Maeda
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Correspondence to Qi Wang.

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Wang, Q., Ishikawa, T., Michiue, T. et al. Molecular pathology of brain matrix metalloproteases, claudin5, and aquaporins in forensic autopsy cases with special regard to methamphetamine intoxication. Int J Legal Med 128, 469–474 (2014). https://doi.org/10.1007/s00414-014-0972-6

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  • DOI: https://doi.org/10.1007/s00414-014-0972-6

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