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Monosodium luminol reinstates redox homeostasis, improves cognition, mood and neurogenesis, and alleviates neuro- and systemic inflammation in a model of Gulf War Illness.

ABSTRACT: Enduring brain dysfunction is amid the highly manifested symptoms in veterans with Gulf War Illness (GWI). Animal studies have established that lasting brain dysfunction in GWI is concomitant with augmented oxidative stress, inflammation, and declined neurogenesis in the brain, and systemic inflammation. We hypothesize that drugs capable of restoring redox homeostasis in GWI will improve cognitive and mood function with modulation of neuroinflammation and neurogenesis. We examined the efficacy of monosodium luminol-GVT (MSL), a drug that promotes redox homeostasis, for improving cognitive and mood function in GWI rats. Young rats were exposed to GWI-related chemicals and moderate restraint stress for four weeks. Four months later, GWI rats received different doses of MSL or vehicle for eight weeks. Behavioral analyses in the last three weeks of treatment revealed that GWI rats receiving higher doses of MSL displayed better cognitive and mood function associated with reinstatement of redox homeostasis. Such restoration was evident from the normalized expression of multiple genes encoding proteins involved in combating oxidative stress in the brain and the return of several oxidative stress markers to control levels in the brain and the circulating blood. Sustained redox homeostasis by MSL also resulted in antiinflammatory and pro-neurogenic effects, which were apparent from reduced densities of hypertrophied astrocytes and activated microglia, and increased neurogenesis with augmented neural stem cell proliferation. Moreover, MSL treatment normalized the concentration of multiple proinflammatory markers in the circulating blood. Thus, MSL treatment reinstated redox homeostasis in an animal model of GWI, which resulted in alleviation of both brain and systemic inflammation, improved neurogenesis, and better cognitive and mood function.

SUBMITTER: Shetty AK

PROVIDER: S-EPMC6888767 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Monosodium luminol reinstates redox homeostasis, improves cognition, mood and neurogenesis, and alleviates neuro- and systemic inflammation in a model of Gulf War Illness.

Shetty Ashok K AK Attaluri Sahithi S Kodali Maheedhar M Shuai Bing B Shetty Geetha A GA Upadhya Dinesh D Hattiangady Bharathi B Madhu Leelavathi N LN Upadhya Raghavendra R Bates Adrian A Rao Xiaolan X

Redox biology 20191118

Enduring brain dysfunction is amid the highly manifested symptoms in veterans with Gulf War Illness (GWI). Animal studies have established that lasting brain dysfunction in GWI is concomitant with augmented oxidative stress, inflammation, and declined neurogenesis in the brain, and systemic inflammation. We hypothesize that drugs capable of restoring redox homeostasis in GWI will improve cognitive and mood function with modulation of neuroinflammation and neurogenesis. We examined the efficacy o ...[more]

PMID: 31778892

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Project description:Introduction: Approximately 25-30% of veterans deployed to Kuwait, 1990-91, report persistent multi-symptom Gulf War Illness (GWI) likely from neurotoxicant exposures. Photobiomodulation (PBM) in red/near-infrared (NIR) wavelengths is a safe, non-invasive modality shown to help repair hypoxic/stressed cells. Red/NIR wavelengths are absorbed by cytochrome C oxidase in mitochondria, releasing nitric oxide (increasing local vasodilation), and increasing adenosine tri-phosphate production. We investigated whether PBM applied transcranially could improve cognition, and health symptoms in GWI. Materials and Methods: Forty-eight (40 M) participants completed this blinded, randomized, sham-controlled trial using Sham or Real, red/NIR light-emitting diodes (LED) applied transcranially. Fifteen, half-hour transcranial LED (tLED) treatments were twice a week (7.5 weeks, in-office). Goggles worn by participant and assistant maintained blinding for visible red. Pre-/Post- testing was at Entry, 1 week and 1 month post- 15th treatment. Primary outcome measures were neuropsychological (NP) tests; secondary outcomes, Psychosocial Questionnaires, including PTSD. Results: Primary Analyses (all participants), showed improvement for Real vs. Sham, for Digit Span Forwards (p < 0.01); and a trend for Trails 4, Number/Letter Sequencing (p < 0.10). For secondary outcomes, Real group reported more improvement on the SF-36V Plus, Physical Component Score (p < 0.08). Secondary Analyses included only subjects scoring below norm (50%ile) at Entry, on specific NP test/s. Real and Sham improved at 1 week after 15th treatment; however, at 1 month, only those receiving Real improved further: Digit Span Total, Forwards and Backwards; Trails 4, Number/Letter Sequencing; California Verbal Learning Test-II, long delay free recall; Continuous Performance Test-II, False Alarm Rate; and Color-Word Interference, Stroop, Trial 3, Inhibition; Sham group worsened, toward Entry values. Only those with more post-traumatic stress disorder (PTSD) symptomatology at Entry, receiving Real, continued to have additional PTSD reduction at 1 month; Sham regressed. Conclusion: This study was underpowered (n = 48), with large heterogeneity at Entry. This likely contributed to significance or trend to significance, for only two of the NP tests (Digit Span Forwards; Trails 4, Number/Letter Sequencing) and only one general health measure, the SF-36V Plus, Physical Component Score. More subjects receiving Real, self-reported increased concentration, relaxation and sleep. Controlled studies with newer, transcranial LED home treatment devices are warranted; this is expected to increase enrollment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01782378.

Dataset Information

Monosodium luminol reinstates redox homeostasis, improves cognition, mood and neurogenesis, and alleviates neuro- and systemic inflammation in a model of Gulf War Illness.

Publications

Monosodium luminol reinstates redox homeostasis, improves cognition, mood and neurogenesis, and alleviates neuro- and systemic inflammation in a model of Gulf War Illness.

Similar Datasets

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