Next Article in Journal
Role of NMR in High Ordered Structure Characterization of Monoclonal Antibodies
Previous Article in Journal
Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery
Article

Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model

1
Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
2
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri-IRCCS, 20156 Milan, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(1), 45; https://doi.org/10.3390/ijms22010045
Received: 7 December 2020 / Revised: 18 December 2020 / Accepted: 19 December 2020 / Published: 22 December 2020
(This article belongs to the Section Molecular Neurobiology)
The complement system is involved in promoting secondary injury after traumatic brain injury (TBI), but the roles of the classical and lectin pathways leading to complement activation need to be clarified. To this end, we aimed to determine the ability of the brain to activate the synthesis of classical and lectin pathway initiators in response to TBI and to examine their expression in primary microglial cell cultures. We have modeled TBI in mice by controlled cortical impact (CCI), a clinically relevant experimental model. Using Real-time quantitative polymerase chain reaction (RT-qPCR) we analyzed the expression of initiators of classical the complement component 1q, 1r and 1s (C1q, C1r, and C1s) and lectin (mannose binding lectin A, mannose binding lectin C, collectin 11, ficolin A, and ficolin B) complement pathways and other cellular markers in four brain areas (cortex, striatum, thalamus and hippocampus) of mice exposed to CCI from 24 h and up to 5 weeks. In all murine ipsilateral brain structures assessed, we detected long-lasting, time- and area-dependent significant increases in the mRNA levels of all classical (C1q, C1s, C1r) and some lectin (collectin 11, ficolin A, ficolin B) initiator molecules after TBI. In parallel, we observed significantly enhanced expression of cellular markers for neutrophils (Cd177), T cells (Cd8), astrocytes (glial fibrillary acidic protein—GFAP), microglia/macrophages (allograft inflammatory factor 1—IBA-1), and microglia (transmembrane protein 119—TMEM119); moreover, we detected astrocytes (GFAP) and microglia/macrophages (IBA-1) protein level strong upregulation in all analyzed brain areas. Further, the results obtained in primary microglial cell cultures suggested that these cells may be largely responsible for the biosynthesis of classical pathway initiators. However, microglia are unlikely to be responsible for the production of the lectin pathway initiators. Immunofluorescence analysis confirmed that at the site of brain injury, the C1q is localized in microglia/macrophages and neurons but not in astroglial cells. In sum, the brain strongly reacts to TBI by activating the local synthesis of classical and lectin complement pathway activators. Thus, the brain responds to TBI with a strong, widespread and persistent upregulation of complement components, the targeting of which may provide protection in TBI. View Full-Text
Keywords: complement component 1q (C1q); complement component 1s (C1s); complement component 1r (C1r); collectin 11; ficolin A; ficolin B; mannose binding lectin A (MBL-A); mannose binding lectin C (MBL-C); cortex; striatum; thalamus; hippocampus complement component 1q (C1q); complement component 1s (C1s); complement component 1r (C1r); collectin 11; ficolin A; ficolin B; mannose binding lectin A (MBL-A); mannose binding lectin C (MBL-C); cortex; striatum; thalamus; hippocampus
Show Figures

Graphical abstract

MDPI and ACS Style

Ciechanowska, A.; Ciapała, K.; Pawlik, K.; Oggioni, M.; Mercurio, D.; De Simoni, M.-G.; Mika, J. Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model. Int. J. Mol. Sci. 2021, 22, 45. https://doi.org/10.3390/ijms22010045

AMA Style

Ciechanowska A, Ciapała K, Pawlik K, Oggioni M, Mercurio D, De Simoni M-G, Mika J. Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model. International Journal of Molecular Sciences. 2021; 22(1):45. https://doi.org/10.3390/ijms22010045

Chicago/Turabian Style

Ciechanowska, Agata, Katarzyna Ciapała, Katarzyna Pawlik, Marco Oggioni, Domenico Mercurio, Maria-Grazia De Simoni, and Joanna Mika. 2021. "Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury—Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model" International Journal of Molecular Sciences 22, no. 1: 45. https://doi.org/10.3390/ijms22010045

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop