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Immunomodulatory response in an experimental model of brain death.

ABSTRACT: Liver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group. We studied two groups: Control and BD (rats subjected to BD by increasing intracranial pressure). After the induction of BD, there was an intense rise in blood pressure followed by a fall. There were no significant differences observed between the groups. Blood tissue and hepatic tissue analyzes showed an increase in plasma concentrations of liver enzymes (AST, ALT, LDH and ALP), in addition to pro-inflammatory cytokines and macrophages in liver tissue in animals submitted to BD. The current study found that BD is a multifaceted process that elicits both a systemic immune response and a local inflammatory response in liver tissue. Our findings strongly suggested that the immunogenicity of plasma and liver increased with time following BD.

SUBMITTER: Santana AC

PROVIDER: S-EPMC10310852 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Immunomodulatory response in an experimental model of brain death.

Santana Alexandre Chagas AC Andraus Wellington W Zimelewicz Oberman Dan D Rabelo Nícollas Nunes NN Silva Filipe Miranda Oliveira FMO Dellê Humberto H Pepineli Rafael R de Moraes Edvaldo Leal EL Scavone Cristoforo C de Sá Lima Larissa L Degaspari Sabrina S Brasil Sérgio S Solla Davi Jorge Fontoura DJF Ruiz Liliane Moreira LM de Oliveira-Braga Karina Andrighetti KA Nepomuceno Natalia Aparecida NA Pêgo-Fernandes Paulo Manuel PM Tullius Stefan Gunther SG Figueiredo Eberval Gadelha EG

Scientific reports 20230629 1

Liver transplantation has come a long way and is now regarded as the gold standard treatment for end-stage liver failure. The great majority of livers utilized in transplantation come from brain-dead donors. A broad inflammatory response characterizes BD, resulting in multiorgan damage. This process is primarily mediated by cytokines, which increase the immunogenicity of the graft. In male Lewis rats, we evaluated the immune response in a BD liver donor and compared it to that of a control group ...[more]

PMID: 37386074

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Project description:IntroductionTraumatic brain injury is a leading cause of injury-related death and morbidity. Multiple clinical and pre-clinical studies have reported various results regarding sex-based differences in TBI. Our accepted rodent model of traumatic brain injury was used to identify sex-based differences in the pathological features of TBI.MethodsMale and female Sprague-Dawley rats were subjected to either controlled-cortical impact (CCI) or sham injury; brain tissue was harvested at different time intervals depending on the specific study. Blood-brain barrier (BBB) analysis was performed using infrared imaging to measure fluorescence dye extravasation. Microglia and splenocytes were characterized with traditional flow cytometry; microglia markers such as CD45, P2Y12, CD32, and CD163 were analyzed with t-distributed stochastic neighbor embedding (t-SNE). Flow cytometry was used to study tissue cytokine levels, and supplemented with ELISAs of TNF-⍺, IL-17, and IL-1β of the ipsilateral hemisphere tissue.ResultsCCI groups of both sexes recorded a higher BBB permeability at 72 hours post-injury than their respective sham groups. There was significant difference in the integrated density value of BBB permeability between the male CCI group and the female CCI group (female CCI mean = 3.08 x 108 ± 2.83 x 107, male CCI mean = 2.20 x 108 ± 4.05 x 106, p = 0.0210), but otherwise no differences were observed. Traditional flow cytometry did not distinguish any sex-based difference in regards to splenocyte cell population after CCI. t-SNE did not reveal any significant difference between the male and female injury groups in the activation of microglia. Cytokine analysis after injury by flow cytometry and ELISA was limited in differences at the time point of 6 hours post-injury.ConclusionIn our rodent model of traumatic brain injury, sex-based differences in pathology and neuroinflammation at specified time points are limited, and only noted in one specific analysis of BBB permeability.

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Immunomodulatory response in an experimental model of brain death.

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Immunomodulatory response in an experimental model of brain death.

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