Journal of neurotrauma最新文献

{"title":"Traumatic Brain Injury and Alzheimer's Disease Biomarkers: A Systematic Review of Findings from Amyloid and Tau Positron Emission Tomography.","authors":"Kaitlyn M Dybing, Cecelia J Vetter, Desarae A Dempsey, Soumilee Chaudhuri, Andrew J Saykin, Shannon L Risacher","doi":"10.1089/neu.2024.0055","DOIUrl":"10.1089/neu.2024.0055","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) has been discussed as a risk factor for Alzheimer's disease (AD) due to its association with AD risk and earlier cognitive symptom onset. However, the mechanisms behind this relationship are unclear. Some studies have suggested TBI may increase pathological protein deposition in an AD-like pattern; others have failed to find such associations. This review covers literature that uses positron emission tomography (PET) of β-amyloid (Aβ) and/or tau to examine individuals with a history of TBI who are at increased risk for AD due to age. A comprehensive literature search was conducted on January 9, 2023, and 26 resulting citations met inclusion criteria. Common methodological concerns included small samples, limited clinical detail about participants' TBI, recall bias due to reliance on self-reported TBI, and an inability to establish causation. For both Aβ and tau, results were widespread but inconsistent. The regions that showed the most compelling evidence for increased Aβ deposition were the cingulate gyrus and cuneus/precuneus. Evidence for elevated tau was strongest in the medial temporal lobe, entorhinal cortex, precuneus, and frontal, temporal, parietal, and occipital lobes. However, conflicting findings across most regions in both Aβ- and tau-PET studies indicate the critical need for future work in expanded samples and with greater clinical detail to offer a clearer picture of the relationship between TBI and protein deposition in older individuals at risk for AD.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"333-348"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the Effect of Repetitive Head Impact Exposure and mTBI on Adolescent Collision Sports Players' Brain with Diffusion Magnetic Resonance Imaging.","authors":"Maryam Tayebi, Eryn Kwon, Josh McGeown, Leigh Potter, Davidson Taylor, Paul Condron, Miao Qiao, Patrick McHugh, Jerome Maller, Poul Nielsen, Alan Wang, Justin Fernandez, Miriam Scadeng, Vickie Shim, Samantha Holdsworth","doi":"10.1089/neu.2024.0064","DOIUrl":"10.1089/neu.2024.0064","url":null,"abstract":"<p><p>Athletes in collision sports frequently sustain repetitive head impacts (RHI), which, while not individually severe enough for a clinical mild traumatic brain injury (mTBI) diagnosis, can compromise neuronal organization by transferring mechanical energy to the brain. Although numerous studies target athletes with mTBI, there is a lack of longitudinal research on young collision sport participants, highlighting an unaddressed concern regarding cumulative RHI effects on brain microstructures. Therefore, this study aimed to investigate the microstructural changes in the brains' of high school rugby players due to repeated head impacts and to establish a correlation between clinical symptoms, cumulative effects of RHI exposure, and changes in the brain's microstructure. We conducted a longitudinal magnetic resonance imaging (MRI) study on 36 male high school rugby players across a season using 3D T1-weighted and multi-shell diffusion MRI sequences, comparing them with 20 matched controls. Players with concussions were separately tracked up to 6 weeks post-injury with three-times scans within this period. The Sport Concussion Assessment Tool (SCAT5) symptom scale assessed mTBI symptoms, and mouthguard-embedded kinematic sensors recorded head impacts. No significant volumetric changes in subcortical structures were found post-rugby season. However, there were substantial differences in mean diffusivity (MD) and axial diffusivity (AD) between the rugby players and controls across widespread brain regions. Diffusion metrics, especially AD, MD, and radial diffusivity of certain brain tracts, displayed strong correlations with SCAT5 symptom severity. Repeated head impacts during a rugby season may adversely affect the structural organization of the brain's white matter. The observed diffusion changes, closely tied to SCAT5 symptom burden, stress the profound effects of seasonal head impacts and highlight individual variability in response to repetitive head impact exposure. To better manage sports-related mTBI and guide return-to-play decisions, comprehensive studies on brain injury mechanisms and recovery post-mTBI/RHI exposure are required.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"349-366"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Growth Hormone Deficiency in Brain-Injured Patients: The Quality of Life Scale-99.","authors":"Stephen Barnard, Ramtilak Gattu, Vijaykumar M Baragi, Opada Alzohaili, Randall Benson","doi":"10.1089/neu.2024.0114","DOIUrl":"10.1089/neu.2024.0114","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (<i>p</i> < 0.006), a reliance on sleep aids (<i>p</i> < 0.011), and feeling overweight (<i>p</i> < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"379-390"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting Subject-Specific Analyses in Neuroimaging Data Using \"Z-Score\" Methods.","authors":"Andrew R Mayer, Andrew B Dodd, Josef M Ling, Edward J Bedrick","doi":"10.1089/neu.2024.0434","DOIUrl":"10.1089/neu.2024.0434","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e461-e462"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' Response to \"Revisiting Subject-Specific Analyses in Neuroimaging Data Using \"Z-Score\" Methods\".","authors":"Sarah I Gimbel, Lars Hungerford, Elizabeth W Twamley, Mark L Ettenhofer","doi":"10.1089/neu.2024.0546","DOIUrl":"10.1089/neu.2024.0546","url":null,"abstract":"","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e463-e464"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Network Functional Connectivity in Response to Sub-Symptomatic Exercise Between Elite Adult Athletes after Sport-Related Concussion and Healthy Matched Controls: A Pilot Study.","authors":"Jessica Coenen, Franziska van den Bongard, Anne Carina Delling, Claus Reinsberger","doi":"10.1089/neu.2023.0629","DOIUrl":"10.1089/neu.2023.0629","url":null,"abstract":"<p><p>Resting-state electroencephalography (rsEEG) has developed as a method to explore functional network alterations related to sport-related concussion (SRC). Although exercise is an integral part of an athlete's return to sport (RTS) protocol, our understanding of the effects of exercise on (impaired) brain network activity in elite adult athletes is limited. However, this information may be beneficial to inform recovery and RTS progressions. Recording (128-channel) rsEEG datasets before and after a standardized moderate aerobic bike exercise test, this study aimed to explore functional connectivity patterns in whole brain and relevant functional networks in a group of elite adult athletes post-injury compared with healthy matched controls. The following networks were selected <i>a priori</i>: whole brain (68 regions of interest [ROIs]), default mode network (14 ROIs), central autonomic network (CAN, 24 ROIs), and visual network (8 ROIs). Twenty-one SRC athletes and 21 age-, sex-, sport type-, and skill level-matched healthy controls participated in this study. The SRC athletes were recruited during their RTS protocol (days since injury: 2-140 days). All athletes were able to achieve the exercise goal of reaching a moderate intensity (70% of their age-calculated maximum heart rate) while staying sub-symptomatic. Before and after exercise, functional connectivity was calculated by the phase locking value, in the alpha band (7-13 Hz). Mann-Whitney U and Wilcoxon signed rank tests were used to explore neurophysiological differences between and within groups, respectively. Whole-brain connectivity increased significantly from pre- to post-exercise within both groups (SRC: 0.264-0.284; <i>p</i> = 0.011 vs. controls: 0.253-0.257; <i>p</i> = 0.011). While CAN connectivity significantly increased only within the SRC group from pre-(0.298) to post-exercise (0.317; <i>p</i> = 0.003). Although all athletes reached their exercise goal without exacerbation of symptoms, the impact of exercise on the CAN appears to be greater for the SRC athletes, than matched healthy controls. The potential clinical significance of this finding is that it may have revealed an underlying mechanism for the cardiac autonomic alterations post-injury. This study merits further investigation into the CAN, as a network of interest more closely aligned with the clinical features (e.g., autonomic dysfunction) during athletes' RTS.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"367-378"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Blood Biomarkers of Targeted Intervention for Chronic Mental Health Symptoms following Traumatic Brain Injury.","authors":"Shawn R Eagle, Sarah E Svirsky, Ava M Puccio, Allison Borrasso, Kathryn Edelman, Sue Beers, Denes Agoston, Ryan Soose, Michael Collins, Anthony Kontos, Walter Schneider, David O Okonkwo","doi":"10.1089/neu.2024.0245","DOIUrl":"10.1089/neu.2024.0245","url":null,"abstract":"<p><p>The purpose of this study was to assess the performance of predictive blood biomarkers for responsiveness to targeted treatments for chronic psychological issues years after traumatic brain injury (TBI). Targeted Evaluation Action and Monitoring of TBI was a prospective 6-month interventional trial of participants with chronic TBI sequelae (<i>n</i> = 95). Plasma biomarkers were analyzed pre-intervention: glial fibrillary acidic protein (GFAP), tau, hyperphosphorylated tau Thr231 (p-Tau), von Willebrand factor (vWF), brain lipid-binding protein (BLBP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), vascular endothelial growth factor-a (VEGFa), and claudin-5 (CLDN5). Clinical outcomes included the Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) and Brief Symptom Inventory-18 (BSI-18). Regression models were built for change in PCL5/BSI-18. Biomarkers and covariates were included. Two models were built to identify responders (improved beyond the minimum clinically important difference). The model to predict change in PCL5 (<i>R</i>²=0.64; <i>p</i> < 0.001) included vWF (<i>p</i> = 0.032), BLBP (<i>p</i> = 0.001), tau (<i>p</i> = 0.002), VEGFa (<i>p</i> = 0.015), female sex (<i>p</i> = 0.06), and military status (<i>p</i> = 0.014). The model to predict change in BSI-18 (<i>R</i>²=0.42; <i>p</i> = 0.003) included vWF (<i>p</i> = 0.042), VEGFa (<i>p</i> = 0.09), BLBP (<i>p</i> = 0.01), CLDN5 (<i>p</i> < 0.001), female sex (<i>p</i> = 0.012), and military status (<i>p</i> = 0.004) as predictors. The model to differentiate participants who improved for PCL5 (<i>R</i>²=0.68; <i>p</i> < 0.001; AUC = 0.93) included vWF (<i>p</i> = 0.02), VEGFa (<i>p</i> = 0.008), and BLBP (<i>p</i> = 0.006). The model to differentiate participants who improved for BSI-18 (<i>R</i>²=0.25; <i>p</i> = 0.04; AUC = 0.75) included UCH-L1 (<i>p</i> = 0.03), GFAP (<i>p</i> = 0.06), and vWF (<i>p</i> = 0.03). Combinations of pre-intervention blood biomarkers were able to differentiate responders from nonresponders in both post-traumatic stress and overall psychological health domains.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e454-e460"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combination of Low Doses of Lithium and Valproate Improves Cognitive Outcomes after Mild Traumatic Brain Injury.","authors":"John B Redell, Mark E Maynard, Michael J Hylin, Kimberly N Hood, Andrea Sedlock, Dragan Maric, Jing Zhao, Anthony N Moore, Badrinath Roysam, Shibani Pati, Pramod K Dash","doi":"10.1089/neu.2024.0311","DOIUrl":"10.1089/neu.2024.0311","url":null,"abstract":"<p><p>The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + VPA) for 3 weeks after a moderate-to-severe controlled cortical impact injury reduced cortical tissue loss and improved motor function. Since both lithium and valproate can exhibit toxicity at high doses, it would be beneficial to determine if this combination treatment is effective when administered at low doses and for a shorter duration, and if it can improve cognitive function, after a mild diffuse TBI. In the present study, we tested if the combination of low doses of lithium (1 mEq/kg or 0.5 mEq/kg) plus valproate (20 mg/kg) administered for 3 days after a mild fluid percussion injury can improve hippocampal-dependent learning and memory. Our data show that the combination of low-dose Li + VPA improved spatial learning and memory, effects not seen when either drug was administered alone. In addition, postinjury Li + VPA treatment improved recognition memory and sociability and reduced fear generalization. Postinjury Li + VPA also reduced the number of anti-ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia counted using a convolutional neural network, indicating a reduction in neuroinflammation. These findings indicate that low-dose Li + VPA administered acutely after mTBI may have translational utility to reduce pathology and improve cognitive function.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"437-453"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes after Traumatic Brain Injury with and Without Computed Tomography.","authors":"Ana Mikolić, Shuyuan Shi, William Panenka, Jeffrey R Brubacher, Frank X Scheuermeyer, Lindsay D Nelson, Noah D Silverberg","doi":"10.1089/neu.2024.0332","DOIUrl":"10.1089/neu.2024.0332","url":null,"abstract":"<p><p>Our recent improved understanding of traumatic brain injury (TBI) comes largely from cohort studies of TBI patients with indication for computed tomography (CT). Using CT head as an inclusion criterion may overestimate poor outcomes after TBI with Glasgow Coma Scale (GCS) 13-15. We aimed to compare outcomes after TBI in adults who had a head CT scan (with negative findings) versus those who had no CT when presenting to an emergency department. This was a secondary analysis of a trial that recruited adults with GCS = 13-15 after TBI in Vancouver, Canada. We included 493 participants (18-69 years, 54% female), after removing <i>n</i> = 19 with traumatic abnormalities on CT (intracranial and/or skull fracture). Outcomes were Glasgow Outcome Scale Extended (GOSE), Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Patient Health Questionnaire (PHQ)-9, and generalized anxiety disorder (GAD)-7 at 6 months post-injury. Over half (55%) of participants received a CT. At 6 months, 55% of participants with CT and 49% without CT had functional limitations on GOSE; 32% with CT and 33% without CT reported severe post-concussion symptoms (RPQ ≥16); 26% (with CT) and 28% (without CT) screened positive for depression (PHQ-9 ≥ 10), and 25% (with CT) and 28% (without CT) screened positive for anxiety (GAD-7 ≥ 8). In regression adjusted for personal variables, participants with CT had somewhat higher odds of worse functioning (ordinal GOSE; 1.4, 95% CI 1.0-2.0) but similar odds of severe post-concussion symptoms (1.1, 95% CI: 0.7-1.7), and depression (1.1, 95% CI: 0.7-1.7) and anxiety (1.0, 95% CI: 0.6-1.5) symptoms. Adults with and without head CT have mostly comparable outcomes from TBI with GCS = 13-15. Requiring CT by clinical indication for study entry may not create problematic selection bias for outcome research.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"391-398"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Opioid Administration Undermines Recovery after SCI: Adverse Effects Are Not Restricted to Morphine.","authors":"Josephina Rau, Rose Joseph, Lara Weise, Jessica Bryan, Jad Wardeh, Alekya Konda, Landon Duplessis, Michelle A Hook","doi":"10.1089/neu.2024.0375","DOIUrl":"https://doi.org/10.1089/neu.2024.0375","url":null,"abstract":"<p><p>Previous studies have shown that administration of high doses of morphine in the acute phase of spinal cord injury (SCI) significantly undermines locomotor recovery and increases symptoms of chronic pain in a rat spinal contusion model. Similarly, SCI patients treated with high doses of opioid for the first 24 h postinjury have increased symptoms of chronic pain 1 year later. Whether these adverse effects are driven by morphine only or all opioids compromise recovery after SCI, however, is unknown. Based on our previous findings we hypothesized that activation of the kappa opioid receptor (KOR) is key in the morphine-induced attenuation of locomotor recovery after SCI. Thus, we posited that opioids that engage KOR-mediated signaling pathways (morphine, oxycodone) would undermine recovery, and clinically relevant opioids with less KOR activity (fentanyl and buprenorphine) would not. To test this, we compared the effects of the clinically relevant opioids on locomotor recovery and pain in a male rat spinal contusion model. Rats were given a moderate spinal contusion injury followed by 7 days of intravenous morphine, oxycodone, fentanyl, buprenorphine, or saline, and recovery was assessed for 28 days. All opioids produced analgesia on tests of thermal, mechanical, and incremented shock reactivity. However, tolerance developed rapidly with buprenorphine administration, particularly with daily administrations of 5 morphine milligram equivalent (MME) buprenorphine. Opioid-induced hyperalgesia (OIH) also developed across days following administration of higher doses (10 MME, 20 MME) of morphine and oxycodone. Fentanyl and buprenorphine did not produce OIH. Contrary to our hypothesis, however, we found that high doses of all opioids reduced recovery of locomotor function. Unlike the other opioids, the effects of buprenorphine on locomotor recovery appeared transient, but it also produced chronic pain. Morphine, oxycodone, and buprenorphine decreased reactivity thresholds on tests of mechanical and incremented shock stimulation. In sum, all opioids undermined long-term recovery in the rat model. Further interrogation of the molecular mechanisms driving the adverse effects is essential. This study provides critical insight into pain management strategies in the acute phase of SCI and potential long-term consequences of early opioid administration.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}