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Hippocampal Microglia Activation Induced by Acute Pancreatic Injury in Rats

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Abstract

Background

Acute pancreatitis is an inflammation of the pancreatic glandular parenchyma that causes injury with or without the destruction of pancreatic acini. Clinical and experimental evidence suggest that certain systemic proinflammatory mediators may be responsible for initiating the fundamental mechanisms involved in microglial reactivity. Here, we investigated the possible repercussions of acute pancreatitis (AP) on the production of inflammatory mediators in the brain parenchyma focusing on microglial activation in the hippocampus.

Methods

The acute pancreatic injury in rats was induced by a pancreas ligation surgical procedure (PLSP) on the splenic lobe, which corresponds to approximately 10% of total mass of the pancreas. Blood samples were collected via intracardiac puncture for the measurement of serum amylase. After euthanasia, frozen or paraffin-embedded brains and pancreas were analyzed using qRT-PCR or immunohistochemistry, respectively.

Results

Immunohistochemistry assays showed a large number of Iba1 and PU.1-positive cells in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus of the PLSP group. TNF-α mRNA expression was significantly higher in the brain from PLSP group. NLRP3 inflammasome expression was found to be significantly increased in the pancreas and brain of rats of the PLSP group. High levels of BNDF mRNA were found in the rat brain of PLSP group. In contrast, NGF mRNA levels were significantly higher in the control group versus PLSP group.

Conclusion

Our findings suggest that AP has the potential to induce morphological changes in microglia consistent with an activated phenotype.

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Acknowledgments

We thank Claudio Sergio Correa Lau Junior and Dr. Marcus Vinicius Alves da Silva for help with animal care. We also thank Dr. Frederick S. Leal for revising the English in the manuscript.

Funding

Financial support for this work was provided by the Graduate Vice-Presidency of Universidade Federal do Rio de Janeiro (CEPG/UFRJ), the Brazilian Council for Science and Technology (CNPq), and the Rio de Janeiro State Foundation for Research Support (FAPERJ).

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Authors and Affiliations

  1. Postgraduate Program in Surgical Science, Department of Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Tamires Cabral-França, Vera Lucia Nunes Pannain, José Marcus Raso Eulálio, Jose Eduardo Ferreira Manso & Wagner Baetas-da-Cruz

  2. Department of Surgery, Centre for Experimental Surgery, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Tamires Cabral-França, Paulo Cesar Silva, José Marcus Raso Eulálio, Jose Eduardo Ferreira Manso & Wagner Baetas-da-Cruz

  3. Translational Laboratory in Molecular Physiology, Department of Surgery, School of Medicine, Centre for Experimental Surgery, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Tamires Cabral-França, Hugo Macedo-Ramos & Wagner Baetas-da-Cruz

  4. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Fernanda Ferreira Cruz & Arlete Fernandes

  5. Department of Pathology, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Vera Lucia Nunes Pannain & Arlete Fernandes

  6. National Institute of Technology, Rio de Janeiro, RJ, Brazil

    Maurício Magalhães Paiva

  7. Laboratório Translacional em Fisiologia Molecular, Faculdade de Medicina, Centro de Cirurgia Experimental, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, CCS, Bloco J, 2º and, Rio de Janeiro, RJ, 21941-902, Brazil

    Wagner Baetas-da-Cruz

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  1. Tamires Cabral-França
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  2. Fernanda Ferreira Cruz
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Contributions

HM-R, FFC, JEFM, and WB-d-C conceived of the study. TC-F performed most of the experiments. FFC and TC-F performed the molecular biology experiments. TC-F and AF performed tissue sample preparation and histology protocols. VLNP, HM-R, and WB-d-C carried out the histological analysis. PCS, TC-F, JMRE, and JEFM developed the model of acute pancreatitis in rats. MMP and WB-d-C conceived of the scheme in Fig. 13, and MMP drew the images. HM-R and WB-d-C wrote the final version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Wagner Baetas-da-Cruz.

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Conflict of interest

The authors declare no confict of interest with regard to the present manuscript.

Ethical approval

The experimental protocol was submitted to the Ethics Committee for the Use of Animals in Scientific Experimentation at the Health Sciences Center of the Federal University of Rio de Janeiro (CEUA-CCS-UFRJ- Registration Number: 01200.001568/2013-87), registered with the National Council for the Control of Animal Experimentation (CONCEA) and approved for execution.

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Cabral-França, T., Cruz, F.F., Silva, P.C. et al. Hippocampal Microglia Activation Induced by Acute Pancreatic Injury in Rats. Dig Dis Sci 69, 148–160 (2024). https://doi.org/10.1007/s10620-023-08167-x

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  • DOI: https://doi.org/10.1007/s10620-023-08167-x

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