Brain Research Bulletin最新文献

{"title":"Impairment of inhibitory control due to repetitive subconcussions from indirect brain impacts: Evidence from event-related potentials and resting-state EEG complexity in parachuters","authors":"","doi":"10.1016/j.brainresbull.2024.111053","DOIUrl":"10.1016/j.brainresbull.2024.111053","url":null,"abstract":"<div><p>The present study aims to investigate the unknown relationship between inhibitory control and repetitive subconcussion induced by the indirect brain impacts. We enrolled 28 parachuters exposed to repetitive subconcussion (SC) and 27 matched health controls (HC). Parachuters who have completed at least 70 actual parachuting (71–112 times) and at least 1500 simulated platform jumps (1500–4500 times) were included in the SC group. The SC group had a reduced accuracy rate in both the Stroop congruent and incongruent conditions. Larger N2 and N450 amplitudes were elicited in the frontal regions of the SC group, which indicate compensatory adaptations to the deficit in conflict monitoring. The reduced frontal resting-state EEG complexity in full-band (1–40 Hz) may demonstrate the frontal structural damage following the indirect brain impacts of repetitive subconcussion. Pearson correlation analysis showed that in the SC group, the frontal beta-band sample entropy values are positively correlated with the accuracy rate of the Stroop incongruent condition, suggesting the frontal beta-band sample entropy values may serve as potential electrophysiological markers of impaired inhibitory control after indirectly repetitive brain impacts. This study provides the robust evidence that repetitive subconcussion resulting from indirect brain impacts may lead to impairment of inhibitory control.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001874/pdfft?md5=44247893a1c7ac77b7a23ac7abbecb42&pid=1-s2.0-S0361923024001874-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ELK4 ameliorates cognitive impairment and neuroinflammation induced by obstructive sleep apnea","authors":"","doi":"10.1016/j.brainresbull.2024.111054","DOIUrl":"10.1016/j.brainresbull.2024.111054","url":null,"abstract":"<div><p>Intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) syndrome elicited neuron injury (especially in the hippocampus and cortex), contributing to cognitive dysfunction. This study investigated the effects and clarified the mechanisms of ETS domain-containing protein Elk-4 (ELK4) on the cognitive function and neuroinflammation of mice with IH. Mouse microglia BV2 cells were induced with IH by exposure to fluctuating O₂ concentrations (alternating from 5 % to 21 % every 30 min), and mice with OSA were developed and subjected to lentivirus-mediated gene intervention. ELK4 expression was significantly reduced in IH-induced microglia and brain tissues of mice with OSA. Overexpression of ELK4 attenuated oxidative stress, decreased the pro-inflammatory factors IL-1β, IL-6, and TNF-α, and increased the level of the anti-inflammatory factors IL-10 and TGF-β1, as well as the neuroprotective factor BDNF. ELK4 promoted the transcription of fibronectin type III domain-containing protein 5 (FNDC5) by binding to the promoter of FNDC5. Knockdown of FNDC5 in IH-induced microglia and animals reversed the protective effects of ELK4 on OSA-associated neuroinflammation and cognitive dysfunction. Overall, the results demonstrated that ELK4 overexpression repressed microglial activation by inducing the transcription of FNDC5, thus attenuating neuroinflammation and cognitive dysfunction induced by OSA.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001886/pdfft?md5=b2917d8cd8edacb0f59b81ab623ea5c8&pid=1-s2.0-S0361923024001886-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered local intrinsic neural activity and molecular architecture in internet use disorders","authors":"","doi":"10.1016/j.brainresbull.2024.111052","DOIUrl":"10.1016/j.brainresbull.2024.111052","url":null,"abstract":"<div><h3>Background</h3><p>Internet gaming disorder (IGD) is mainly characterized by its core dysfunction in higher-order brain cortices involved in inhibitory control, whose neurobiological basis remains unclear. Then, we will investigate local intrinsic neural activity (INA) alterations in IGD, ascertain whether these potential alterations are related to clinical characteristics, and further explore the underlying molecular architecture.</p></div><div><h3>Method</h3><p>In this study, we performed the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) derived from resting-state functional magnetic resonance imaging (rs-fMRI) to explore the impact of IGD on local INA. Correlation analysis revealed the relationship between ReHo and fALFF in terms of group differences and clinical characteristics. Moreover, correlations between fALFF, ReHo, and PET- and SPECT-driven maps were investigated to elucidate the specific molecular architecture alternations in IGD. Finally, receiver operating characteristic curve (ROC) analysis was used to show the potential abilities of fALFF and ReHo in distinguishing individuals with IGD (IGDs) from healthy controls (HCs).</p></div><div><h3>Result</h3><p>Compared with HCs, IGDs revealed increased ReHo and fALFF in the prefrontal cortex. Significantly decreased ReHo was observed in the temporal lobe, occipital lobe, and cerebellum. In addition, the ReHo values in the cerebellum_7b_R were positively correlated with internet addiction severity. ROC curve analysis showed that ReHo and fALFF-altered brain regions could effectively distinguish IGDs from HCs. More importantly, cross-modal correlations revealed local INA changes in brain regions associated with the monoamine neurotransmitter system and the less studied cholinergic/GABAergic system.</p></div><div><h3>Conclusion</h3><p>These results suggest that local functional impairments are shown in the audiovisual and inhibitory control circuits in IGDs. This may be associated with underlying neurotransmitter system alterations. Therefore, this study provides the possibility of GABAergic receptor agonists and cholinergic receptor inhibitors for the treatment of IGD.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001862/pdfft?md5=dde8fce7a05dff13f3ae207a264f714d&pid=1-s2.0-S0361923024001862-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Prepubertal exposure to Pb alters autophagy in the brain of aging mice: A time-series based model” [Brain Res. Bull. 189 (2022) 22–33]","authors":"","doi":"10.1016/j.brainresbull.2024.111051","DOIUrl":"10.1016/j.brainresbull.2024.111051","url":null,"abstract":"","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001850/pdfft?md5=cf9c2af87ae2e4a9d2a94d1e4220f9ba&pid=1-s2.0-S0361923024001850-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1 mediates microglia polarization via the MAPK signaling pathway to protect blood-brain barrier function during cerebral ischemia/reperfusion","authors":"","doi":"10.1016/j.brainresbull.2024.111055","DOIUrl":"10.1016/j.brainresbull.2024.111055","url":null,"abstract":"<div><h3>Background</h3><p>Cerebral ischemia is characterized by its rapid onset and high rates of recurrence, morbidity, and mortality, with blood-brain barrier (BBB) permeability playing a vital role in brain injury. Therefore, it is important to understand the molecular mechanism which regulates the BBB during cerebral ischemia.</p></div><div><h3>Materials and methods</h3><p>An <em>in vitro</em> model of oxygen-glucose deprivation (OGD) and an <em>in vivo</em> model of cerebral ischemia/reperfusion (I/R) were constructed. PD-1 overexpression vectors and vectors containing si-RNA were transfected and injected into <em>in vitro</em> and <em>in vivo</em> models. Western blotting, real-time quantitative PCR (qPCR), immunofluorescence (IF) analysis, and immunohistochemical staining were employed to evaluate the expression levels of programmed cell death-1 (PD-1), microglia M1 and M2 biomarkers, and tight junction proteins. Flow cytometry and ELISA were used to measure the levels of pro-inflammatory cytokines. The BBB permeability of brain tissues was evaluated by Evans blue dye (EBD) extravasation and transendothelial electrical resistance (TEER). Brain water content was measured to assess the extent of inflammatory exudation. The infarct volume and neurological severity score (NSS) were used to assess the severity of brain injury. Brain cell apoptosis was assessed by the TUNEL assay and hematoxylin-eosin (H&amp;E) staining.</p></div><div><h3>Results</h3><p>PD-1 helped to convert the microglia M1 phenotype to the M2 phenotype and to reduce BBB permeability both <em>in vitro</em> and <em>in vivo</em>. Overexpression of PD-1 promoted a shift of the M1 phenotype to the M2 phenotype and reduced BBB permeability via the ERK and p38 MAPK signaling pathways. PD-1 reduced inflammatory exudation, BBB permeability, cell apoptosis, and brain injury <em>in vivo</em>.</p></div><div><h3>Conclusion</h3><p>Our present study verified that PD-1 exerts an anti-inflammatory effect by converting the microglia M1 phenotype to the M2 phenotype, reducing BBB permeability, and thereby relieves brain injury caused by cerebral ischemia. PD-1 is potential therapeutic target for brain injury caused by cerebral ischemia.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001898/pdfft?md5=9f59e8f8342b70da3651d5f2ad31f2a8&pid=1-s2.0-S0361923024001898-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of GPR68 against cerebral ischemia-reperfusion injury via the NF-κB/Hif-1α pathway","authors":"","doi":"10.1016/j.brainresbull.2024.111050","DOIUrl":"10.1016/j.brainresbull.2024.111050","url":null,"abstract":"<div><h3>Background</h3><p>G protein-coupled receptor 68 (GPR68), an orphan receptor, has emerged as a promising therapeutic target for mitigating neuronal inflammation and oxidative damage. This study explores the protective mechanisms of GPR68 in cerebral ischemia-reperfusion injury (CIRI).</p></div><div><h3>Methods</h3><p>An <em>in vivo</em> middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. Mice received intraperitoneal injections of Ogerin, a selective GPR68 agonist. <em>In vitro</em>, GPR68 was overexpressed in SH-SY5Y and HMC3 cells, and the effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cell viability were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry.</p></div><div><h3>Results</h3><p>The expression of GPR68 was suppressed in cells subjected to OGD/R treatment, whereas its upregulation conferred protection to SH-SY5Y and HMC3 cells. <em>In vivo</em>, levels of GPR68 were reduced in brain tissues affected by MCAO/R, correlating with oxidative stress, inflammation, and neurological damage. Treatment with a GPR68 agonist decreased brain infarction, apoptosis, and dysregulated gene expression induced by MCAO/R. Mechanistically, GPR68 agonist treatment may inhibit the activation of the NF-κB/Hif-1α pathway, thereby reducing oxidative and inflammatory responses and enhancing protection against CIRI.</p></div><div><h3>Conclusions</h3><p>This study confirms that the GPR68/NF-κB/Hif-1α axis modulates apoptosis, inflammation, and oxidative stress in CIRI, indicating that GPR68 is a potential therapeutic target for CIRI.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001837/pdfft?md5=ef11d79206961df7cef8804c31a6e55d&pid=1-s2.0-S0361923024001837-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RBM5 induces motor neuron apoptosis in hSOD1G93A-related amyotrophic lateral sclerosis by inhibiting Rac1/AKT pathways","authors":"","doi":"10.1016/j.brainresbull.2024.111049","DOIUrl":"10.1016/j.brainresbull.2024.111049","url":null,"abstract":"<div><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1^G93A-NSC34 cell models and hSOD1^G93A mice due to a reduction of miR-141–5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1^G93A-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001825/pdfft?md5=c50bab576f451862934624a0c51aca61&pid=1-s2.0-S0361923024001825-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Our brains sense the future through a new quantum-like implicit learning mechanism","authors":"","doi":"10.1016/j.brainresbull.2024.111048","DOIUrl":"10.1016/j.brainresbull.2024.111048","url":null,"abstract":"<div><h3>Background</h3><p>Imagine if our brains could unconsciously predict future events. This study explores this concept, presenting evidence for an inherent 'foreseeing' ability, termed <em>anomalous cognition</em> (AC). We introduce a new experimentally verifiable approach to explain <em>anomalous information anticipation</em> (AIA), a type of AC, based on an innovative, <em>quantum-like</em> model of implicit learning, grounded in <em>Nonlocal Plasticity Theory</em> (NPT).</p></div><div><h3>Methods</h3><p>Our research involved 203 participants using methods such as continuous flash suppression, random dot motion, and advanced 3D EEG neuroimaging, along with IBM quantum random event generators for precise measurements across 144 trials. These trials tested contingencies between undetectable sensory stimuli and dot movements, focusing on participants' prediction abilities. The design conditions were strictly experimental, violating fundamental classical learning principles, particularly reflex conditioning. If these principles were immutable, their violation would prevent any systematic behavioral changes, resulting in random responses. This violation was implemented through two quantum physics concepts: the mathematical principle of <em>nonlocality</em> and <em>entanglement</em>.</p></div><div><h3>Results</h3><p>Despite the sensory stimulus being inaccessible, our results showed a significant prediction between the contingencies and an increase in AIA accuracy, with explained variances between 25 % and 48 %. EEG findings supported this, showing a positive link between brain activity in specific regions and AIA success. Electrochemical activations were detected in the <em>posterior occipital cortex</em>, the <em>intraparietal sulcus</em>, and the <em>medial temporal gyri</em>. AIA hits exceeded the threshold value corresponding to one standard deviation above the expected mean, showing moderate effect sizes in the experimental group (Cohen’s <em>d</em> = 0.461). Analyzing the learning curve using the derivation technique, we identified the acceleration point of the wave function, indicating systematic implicit learning. This result showed that from repetition 63 onwards, AIA hits increased significantly.</p></div><div><h3>Conclusions</h3><p>The results suggest that, despite violating fundamental classical learning principles, cognitive processes produced changes in participants' responses susceptible to neuromodulation, considering quantum physics principles of nonlocality and entanglement (both present in NPT). We discuss (a) why the <em>priming</em> effect does not explain the significant results; (b) the potential discovery of a new form of quantum-like implicit learning, which could scientifically resolve phenomena associated with anomalous cognitions (e.g., AIA); and (c) future research directions, including potential applications and clinical impact.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001813/pdfft?md5=5dc3bfcbf07b4db041aa3459d4a1f38c&pid=1-s2.0-S0361923024001813-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 ameliorates cerebral ischemia-reperfusion injury by regulating Pink1/ Parkin-mediated mitochondrial autophagy and inhibiting microglia NLRP3 activation","authors":"","doi":"10.1016/j.brainresbull.2024.111043","DOIUrl":"10.1016/j.brainresbull.2024.111043","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to further elucidate the mechanism of ginsenoside Rg1 in the treatment of cerebral ischemia-reperfusion.</p></div><div><h3>Methods</h3><p>In this study, we observed the apoptosis of RM cells (microglia) after oxygen-glucose deprivation/reoxygenation (OGD/R) modeling before and after Rg1 administration, changes in mitochondrial membrane potential, changes in the content of Reactive oxygen species (ROS) and inflammatory vesicles NLR Family Pyrin Domain Containing 3 (NLRP3), and the expression levels of autophagy-related proteins, inflammatory factors, and apoptosis proteins. We further examined the pathomorphological changes in brain tissue, neuronal damage, changes in mitochondrial morphology and mitochondrial structure, and the autophagy-related proteins, inflammatory factors, and apoptosis proteins expression levels in CI/RI rats before and after administration of Rg1 in vivo experiments.</p></div><div><h3>Results</h3><p>In vitro experiments showed that Rg1 induced mitochondrial autophagy, decreased mitochondrial membrane potential, and reduced ROS content thereby inhibiting NLRP3 activation, decreasing secretion of inflammatory factors and RM cell apoptosis by regulating the PTEN induced putative kinase 1(Pink1) /Parkin signaling pathway. In vivo experiments showed that Rg1 induced mitochondrial autophagy, inhibited NLRP3 activation, improved inflammatory response, and reduced apoptosis by regulating the Pink1/Parkin signaling pathway, and Rg1 significantly reduced the area of cerebral infarcts, improved the pathological state of brain tissue, and attenuated the neuronal damage, thus improving cerebral ischemia/reperfusion injury in rats.</p></div><div><h3>Conclusion</h3><p>Our results suggest that ginsenoside Rg1 can ameliorate cerebral ischemia-reperfusion injury by modulating Pink1/ Parkin-mediated mitochondrial autophagy in microglia and inhibiting microglial NLRP3 activation.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S036192302400176X/pdfft?md5=c67268e14af8b9f9d181975406b0b546&pid=1-s2.0-S036192302400176X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial","authors":"","doi":"10.1016/j.brainresbull.2024.111047","DOIUrl":"10.1016/j.brainresbull.2024.111047","url":null,"abstract":"<div><h3>Background</h3><p>Immune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies.</p></div><div><h3>Objective</h3><p>To evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects.</p></div><div><h3>Methods</h3><p>This 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis.</p></div><div><h3>Results</h3><p>There were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ²=1.9, P =.48) or a significant time × treatment interaction (χ²=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups’ reduction in HAM-D-17 scores from the start to the endpoint (χ²= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ²=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP&gt; 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ²=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and &lt;.001, respectively).</p></div><div><h3>Conclusion</h3><p>The current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.</p></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0361923024001801/pdfft?md5=d4d815bccfc47419992bc7e0ad234437&pid=1-s2.0-S0361923024001801-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}