Evidence map›Paper›PMID 40474026›Full record

ArticleMolecular neurobiology2025

Neuroprotective Role of Ketamine in Reducing Neuroinflammation and Enhancing Neuroplasticity Against a Cortisol-Induced In Vitro Stress Model.

Lucas Santos, Fernanda Dos Santos Petry, Carolina Saibro-Girardi, Júlia Hansen, Danielle Martins, Nicole Fröhlich, Luana Possa, Luiz Filipe Bastos Mendes, Hémelin Resende Farias, Alberto Martins Silva and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Lucas SantosCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. lucassantos_17@hotmail.com.
Fernanda Dos Santos PetryCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Carolina Saibro-GirardiCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Júlia HansenCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Danielle MartinsCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Nicole FröhlichCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Luana PossaCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Luiz Filipe Bastos MendesCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Hémelin Resende FariasLaboratório de Investigação de Desordens Metabólicas e Doenças Neurodegenerativas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Alberto Martins SilvaCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Izabbela Giacon DeitosCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Reykla Ramon BittencourtCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Jade de OliveiraLaboratório de Investigação de Desordens Metabólicas e Doenças Neurodegenerativas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Daniel Pens GelainCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Roberto F AlmeidaCentro de Ciências Químicas Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
José Cláudio Fonseca MoreiraCentro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 407314/2023-7Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul 16/2551-0000499-4
6 · The paper itself

Abstract

Stress is widely recognized as a major environmental factor contributing to the development of mood disorders. In patients with Major Depressive Disorder (MDD) and suicidal behavior, significant hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis is observed, characterized by excessive cortisol release, which in turn stimulates the production of pro-inflammatory mediators. Inflammation affects approximately one in four patients with MDD and is associated with treatment resistance. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist used in patients with severe and treatment-resistant MDD, has emerged as a relevant target for investigation. However, the precise mechanism of action of this drug remains unclear. In this study, we investigated the neuroprotective effects of ketamine in response to cortisol using in vitro stress models with neural-like cells. We observed that cortisol reduced cell viability, increased the expression of inflammatory genes such as NF-κB and NLRP3, and enhanced the production of reactive oxygen species. Additionally, cortisol impaired neuroplasticity by reducing BDNF expression and diminishing the number and length of primary and secondary neurites, as well as overall neural connectivity. Ketamine was found to prevent, attenuate, and even reverse cortisol-induced expression of inflammatory genes and reactive species production. Moreover, ketamine significantly increased BDNF expression and promoted the growth and elongation of primary neurites and neural connections. For the first time, using an in vitro model of cortisol-induced stress in neural-like cells, we demonstrated that ketamine's mechanism of action extends beyond NMDA receptor antagonism to include the reduction of neuroinflammation and the enhancement of neuroplasticity.

Indexed as

HydrocortisoneKetamineModels, BiologicalNeuroinflammatory DiseasesNeuronal PlasticityNeuroprotective AgentsAnimalsBrain-Derived Neurotrophic FactorCell SurvivalHumansInflammationNeuritesReactive Oxygen SpeciesReceptors, N-Methyl-D-AspartateBrain-Derived Neurotrophic FactorHydrocortisoneKetamineNeuroprotective AgentsReactive Oxygen SpeciesReceptors, N-Methyl-D-AspartateBDNFCortisolKetamineNF-κBNLRP3Stress

Identifiers

PMID40474026

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.