ArticleJournal of neuroscience research2020
Modification of kynurenine pathway via inhibition of kynurenine hydroxylase attenuates surgical brain injury complications in a male rat model.
Article in Journal of neuroscience research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- The role of the kynurenine pathway in the pathogenesis of pain and affective disorders after traumatic brain injury.Brain, behavior, & immunity - health · 2026Review
- Modulation of the Kynurenine Pathway: A New Approach for Treating Neurodegeneration.Life (Basel, Switzerland) · 2026Review
- KMO Inhibition Improves Seizures and Depressive-like Behaviors Without Aggravating Cognitive Impairment in Epileptic Mice.Current issues in molecular biology · 2025Article
- Inhibition of HDAC3 induces neuroprotection by activating the Npas4 signaling pathway following surgical brain injury in rats.Iranian journal of basic medical sciences · 2025Article
- Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.Pharmacological reviews · 2024Review
- Effects of Dexmedetomidine on Cognitive Function, Oxidative Stress and Brain Protection in Patients Undergoing Craniocerebral Surgery.Actas espanolas de psiquiatria · 2024Article
- Possible role of Sox11 in a rat model of surgical brain injury.Iranian journal of basic medical sciences · 2024Article
- Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease.Biomedicines · 2023Article
- Tryptophan Metabolism in Central Nervous System Diseases: Pathophysiology and Potential Therapeutic Strategies.Aging and disease · 2023Review
- C-Reactive protein and the kynurenic acid to quinolinic acid ratio are independently associated with white matter integrity in major depressive disorder.Brain, behavior, and immunity · 2022Article
- The Kynurenine Pathway in Traumatic Brain Injury: Implications for Psychiatric Outcomes.Biological psychiatry · 2022Review
- Kynurenine Pathway Metabolites as Biomarkers in Alzheimer's Disease.Disease markers · 2022Review
- Heterocyclic Cathinones as Inhibitors of Kynurenine Aminotransferase II-Design, Synthesis, and Evaluation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Review
- Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases.Archives of biochemistry and biophysics · 2021Review
- Targeting gut dysbiosis as a means to enhance recovery from surgical brain injury.Surgical neurology international · 2021Review
- Overexpression of Mfsd2a attenuates blood brain barrier dysfunction via Cav-1/Keap-1/Nrf-2/HO-1 pathway in a rat model of surgical brain injury.Experimental neurology · 2020Article
- Surgically-induced brain injury: where are we now?Chinese neurosurgical journal · 2019Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neurosurgical procedures result in surgically induced brain injury (SBI) that causes postoperative complications including brain edema and neuronal apoptosis in the surrounding brain tissue. SBI leads to the release of cytokines that indirectly cause the stimulation of kynurenine 3-monooxygenase (KMO) and the release of neurotoxic quinolinic acid (QUIN). This study tested a KMO inhibitor, RO 61-8048, to prevent postoperative brain edema and consequent neuronal apoptosis in an in vivo model of SBI. A rodent model of SBI was utilized which involves partial resection of the right frontal lobe. A total of 127 Sprague-Dawley male rats (weight 275-325 g) were randomly divided into the following groups: Sham surgical group, SBI, SBI + DMSO, SBI + RO 61-8048 (10 mg/kg), SBI + RO 61-8048 (40 mg/kg), and SBI + RO 61-8048 (40 mg/kg) + KAT II inhibitor PF-04859989 (5 mg/kg). RO 61-8048 was administered by intraperitoneal injection after SBI. Postoperative assessment at different time points included brain water content (brain edema), neurological scoring, and western blot. SBI increased brain water content (ipsilateral frontal lobe), decreased neurological function, and increased apoptotic markers compared with sham animals. Treatment with RO 61-8048 (40 mg/kg) reduced brain water content and improved long-term neurological function after SBI. RO 61-8048 increased the expression of kynurenic acid while reducing QUIN and apoptotic markers in the surrounding brain tissue after SBI. These neuroprotective effects were reversed by PF-04859989. This study suggests KMO inhibition via RO 61-8048 as a potential postoperative therapy following neurosurgical procedures.
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