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Pharmaceuticals
Volume 18
Issue 9
10.3390/ph18091298
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review

by
Gustavo N. Silva
1,*,
Virna G. A. Brandão
1,
Kenneth Blum
2,
Kai-Uwe Lewandrowski
3,4 and
Rossano K. A. Fiorelli
5
1
Department of Anesthesiology, Gaffrée e Guinle Universitary Hospital (EBSERH), Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 22290-240, RJ, Brazil
2
Division of Addiction Research & Education, Center for Sports, Exercise & Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
3
Center for Advanced Spine Care of Southern Arizona Tucson, AZ 85712, USA
4
Surgical Institute of Tucson, Tucson, AZ 85711, USA
5
Department of General and Specialized Surgery, Gaffrée e Guinle Universitary Hospital (EBSERH), Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 22290-240, RJ, Brazil
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2025, 18(9), 1298; https://doi.org/10.3390/ph18091298
Submission received: 7 July 2025 / Revised: 16 August 2025 / Accepted: 25 August 2025 / Published: 29 August 2025
(This article belongs to the Special Issue Pharmacological Insight into NMDA Receptor Antagonists)
Versions Notes

Abstract

Ketamine, a widely used anesthetic with emerging evidence suggesting neuroprotective and anti-inflammatory properties across various neurological disorders, is recognized for its NMDA receptor antagonism. It has been postulated to play a role in neuroprotection, due to its anti-inflammatory properties, and decrease microglial activation, as well as cytokines TNF and IL-6. Despite its established role, the extent of ketamine’s effects on neuroinflammation and neuroprotection remains to be fully elucidated. Here, we conducted a narrative review synthesizing current knowledge on ketamine’s operating mechanisms, including its modulation of synaptic plasticity, excitotoxicity, and cytokine release, alongside its therapeutic applications in traumatic brain injury, neurodegenerative diseases, psychiatric disorders, and pain management. For this narrative review, we searched the Medline, Embase, Scopus, Web of Science, and PubMed databases. Our findings indicate that ketamine reduces excitotoxicity and inflammation, which may contribute to neuroprotection in acute neurological injuries. These insights underscore ketamine’s potential as an adjunctive neuroprotective agent, warranting further clinical investigation to optimize its therapeutic utility across neurological and psychiatric contexts.
Keywords: neuroprotection; neuroinflammation; NMDA receptors; brain injury; ketamine neuroprotection; neuroinflammation; NMDA receptors; brain injury; ketamine

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MDPI and ACS Style

Silva, G.N.; Brandão, V.G.A.; Blum, K.; Lewandrowski, K.-U.; Fiorelli, R.K.A. Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review. Pharmaceuticals 2025, 18, 1298. https://doi.org/10.3390/ph18091298

AMA Style

Silva GN, Brandão VGA, Blum K, Lewandrowski K-U, Fiorelli RKA. Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review. Pharmaceuticals. 2025; 18(9):1298. https://doi.org/10.3390/ph18091298

Chicago/Turabian Style

Silva, Gustavo N., Virna G. A. Brandão, Kenneth Blum, Kai-Uwe Lewandrowski, and Rossano K. A. Fiorelli. 2025. "Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review" Pharmaceuticals 18, no. 9: 1298. https://doi.org/10.3390/ph18091298

APA Style

Silva, G. N., Brandão, V. G. A., Blum, K., Lewandrowski, K.-U., & Fiorelli, R. K. A. (2025). Ketamine’s Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review. Pharmaceuticals, 18(9), 1298. https://doi.org/10.3390/ph18091298

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