Traumatic Brain Injury and Opioids: Twin Plagues of the Twenty-First Century

Jammoul, Maya; Jammoul, Dareen; Wang, Kevin K.; Kobeissy, Firas; Depalma, Ralph G.

doi:10.1016/j.biopsych.2023.05.013

Cited by 3 publications

(1 citation statement)

References 103 publications

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“…Opioids remain the core of management for severe headaches for many patients with ABI [7][8][9][10], despite the potential negative impact of opioids on neurologic examination [11] and recovery [12]. Alarmingly, patients with ABI may be uniquely susceptible to opioid misuse [13,14], emphasizing the need for analgesic alternatives.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review

Comparan,

Khaliq,

Frota

et al. 2024

Preprint

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Background: Headache management after acute brain injury (ABI) is challenging. While opioids are commonly used, selective cyclooxygenase-2 inhibitors (COXIBs) may be promising alternatives. However, concerns about cardiovascular effects and bleeding risk have limited their use. We aimed at summarizing available data on efficacy of COXIBs for headache management following ABI. Methods: A systematic review was conducted through MEDLINE and Embase for articles published through 09/2023 (PROSPERO CRD42022320453). No language filters were applied to the initial searches. Interventional or observational studies and systematic reviews assessing efficacy of COXIBs for headache in adults with ABI were eligible. Article selection was performed by two independent reviewers using Distiller SR®. Descriptive statistics were used for data analysis, while meta-analysis was unfeasible due to study heterogeneity. Results: Of 3190 articles identified, six studies met inclusion criteria: four randomized controlled trials and two retrospective cohort studies, all conducted in neurosurgical patients (total n=738) between 2006-2022. Five studies used COXIBs in the intervention group only. Of the six studies, four found a reduction in overall pain scores in the intervention group, while one showed improvement only at 6 hours postoperative, and one did not find significant differences. Pain scores decreased between 4-15%, the largest shift being from moderate to mild severity. Three studies found an overall opioid use reduction throughout hospitalization in the intervention group, while one reported a reduction at 12 hours postoperative only. Opioid consumption decreased between 9-90%. Two studies found a decrease in hospital-length-of-stay by ~1 day in the intervention group. The one study reporting postoperative hemorrhage found a statistically non-significant 3% reduction in the intervention group. Conclusions: In adults with ABI, COXIBs may serve as opioid-sparing adjunctive analgesics for headache control, with limited but pointed data to indicate efficacy in the post-neurosurgical setting. However, further safety data remains to be elucidated.

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Section: Introductionmentioning

confidence: 99%

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review

Comparan,

Khaliq,

Frota

et al. 2024

Preprint

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show abstract

Cyclooxygenase 2 Inhibitors for Headache After Elective Cranial Neurosurgery: Results from a Systematic Review of Efficacy of Cyclooxygenase 2 Inhibitors for Headache After Acute Brain Injury

Comparan,

Khaliq,

Frota

et al. 2024

Neurocrit Care

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Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome

He,

Zhang,

et al. 2024

CNS Neurosci Ther

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BackgroundInflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)‐γ is known to cause microglial priming, but the mechanism is unclear.MethodsWe examined the effects of IFN‐γ on gene expression, microglial activation, inflammatory and immune responses and activity of the NLRP3 inflammasome in primary microglia and in the brains of mice.ResultsOur results showed that treating microglial cultures with IFN‐γ induced a hedgehog‐like morphology and upregulated markers of microglial activation (CD86, CD11b) and pro‐inflammatory molecules (IL‐1β, IL‐6, TNF‐α, iNOS), while downregulating markers of microglial homeostasis (CX3CR1, CD200R1), anti‐inflammatory molecules (MCR1, Arg‐1) and neurotrophic factors (IGF‐1, BDNF). IFN‐γ also upregulated markers of NLRP3 inflammasome activation (NLRP3, caspase‐1, gasdermin D, IL‐18). This particular transcriptional profiling makes IFN‐γ‐primed microglia with exaggerated responses upon lipopolysaccharide (LPS) stimulation. The level of NLRP3, caspase‐1, gasdermin D, IL‐1β, IL‐18, TNF‐α and iNOS in microglia cultures treated with both IFN‐γ and LPS were highest than with either one alone. Injecting IFN‐γ into the lateral ventricle of mice induced similar morphological and functional changes in hippocampal microglia as in primary microglial cultures. The effects of IFN‐γ on NLRP3 inflammasome and microglia from cultures or hippocampus were abolished when STAT1 was inhibited using fludarabin. Injecting mice with IFN‐γ alone or together with LPS induced anxiety‐ and depression‐like behaviors and impaired hippocampus‐dependent spatial memory; these effects were mitigated by fludarabin.ConclusionsIFN‐γ primes microglia by activating STAT1, which upregulates genes that activate the NLRP3 inflammasome. Inhibiting the IFN‐γ/STAT1 axis may be a way to treat neurodegenerative diseases and psychiatric disorders that involve microglial priming.

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Traumatic Brain Injury and Opioids: Twin Plagues of the Twenty-First Century

Cited by 3 publications

References 103 publications

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review

Efficacy of Cyclooxygenase-2 Inhibitors for Headache in Acute Brain Injury: A Systematic Review

Cyclooxygenase 2 Inhibitors for Headache After Elective Cranial Neurosurgery: Results from a Systematic Review of Efficacy of Cyclooxygenase 2 Inhibitors for Headache After Acute Brain Injury

Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome

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