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Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation

Hansson, Elisabeth and Werner, Tony and Björklund, Ulrika and Skiöldebrand, Eva (2016). Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation. IBRO Reports. 1 , 1-9
[Journal article]

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Abstract

This study aimed to test pharmaceutical compounds targeting astrocytes showing inflammatory dysregulation. The primary rat brain cultures were treated with different batches of serum with or without microglia added to make the cells inflammatory-reactive. Lipopolysaccharide (LPS) and tryptase were used as inflammatory inducers. Expression levels of Toll-like receptor 4 (TLR4), Na+/K+-ATPase, and matrix metalloprotease-13 (MMP-13), as well as actin filament organization, pro-inflammatory cytokines, and intracellular Ca2+ release, were evaluated. LPS combined with tryptase upregulated TLR4 expression, whereas Na+/K+-ATPase expression was downregulated, ATP-evoked Ca2+ transients were increased, actin filaments were reorganized and ring structures instead of stress fibers were observed. Other aims of the study were to prevent astrocytes from becoming inflammatory-reactive and to restore inflammatory dysregulated cellular changes. A combination of the m-opioid antagonist (-)-naloxone in ultra-low concentrations, the non-addictive m-opioid agonist (-)-linalool, and the anti-epileptic agent levetiracetam was examined. The results indicated that this drug cocktail prevented the LPS- and tryptase-induced inflammatory dysregulation. The drug cocktail could also restore the LPS- and tryptasetreated cells back to a normal physiological level in terms of the analyzed parameters.

Authors/Creators:Hansson, Elisabeth and Werner, Tony and Björklund, Ulrika and Skiöldebrand, Eva
Title:Therapeutic innovation: Inflammatory-reactive astrocytes as targets of inflammation
Year of publishing :2016
Volume:1
Page range:1-9
Number of Pages:9
Publisher:Elsevier, International Brain Research Organization
ISSN:2451-8301
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Neurosciences
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Pharmaceutical Sciences
Keywords:Astrocytes, Inflammation, Ca2+ signaling, Actin filament, (-)-Naloxone, (-)-Linalool, Levetiracetam
URN:NBN:urn:nbn:se:slu:epsilon-p-99537
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-99537
Additional ID:
Type of IDID
DOI10.1016/j.ibror.2016.06.001
ID Code:16131
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:24 May 2019 07:20
Metadata Last Modified:27 May 2020 03:21

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