Journal of neurotraumaPub Date : 2024-09-01Epub Date: 2024-04-18DOI: 10.1089/neu.2023.0353
Joseph F Welch, Alicia K Vose, Kate Cavka, Gina Brunetti, Louis A DeMark, Hannah Snyder, Clayton N Wauneka, Geneva Tonuzi, Jayakrishnan Nair, Gordon S Mitchell, Emily J Fox
{"title":"Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.","authors":"Joseph F Welch, Alicia K Vose, Kate Cavka, Gina Brunetti, Louis A DeMark, Hannah Snyder, Clayton N Wauneka, Geneva Tonuzi, Jayakrishnan Nair, Gordon S Mitchell, Emily J Fox","doi":"10.1089/neu.2023.0353","DOIUrl":"10.1089/neu.2023.0353","url":null,"abstract":"<p><p>Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O<sub>2</sub> ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O<sub>2</sub> ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (<i>p</i> < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (<i>p</i> = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (<i>p</i> = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, <i>n</i> = 11), whereas others responded minimally (<0.20 L/min/%, <i>n</i> = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH <i>p</i> > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2114-2124"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101802","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}
Journal of neurotraumaPub Date : 2024-09-01Epub Date: 2024-07-29DOI: 10.1089/neu.2023.0555
Simon Schading-Sassenhausen, Dario Pfyffer, Lynn Farner, Andreas Grillhösl, Orpheus Mach, Doris Maier, Lukas Grassner, Iris Leister, Armin Curt, Patrick Freund
{"title":"Extent of Traumatic Spinal Cord Injury Is Lesion Level Dependent and Predictive of Recovery: A Multicenter Neuroimaging Study.","authors":"Simon Schading-Sassenhausen, Dario Pfyffer, Lynn Farner, Andreas Grillhösl, Orpheus Mach, Doris Maier, Lukas Grassner, Iris Leister, Armin Curt, Patrick Freund","doi":"10.1089/neu.2023.0555","DOIUrl":"10.1089/neu.2023.0555","url":null,"abstract":"<p><p>Assessing the extent of the intramedullary lesion after spinal cord injury (SCI) might help to improve prognostication. However, because the neurological level of injury impacts the recovery potential of SCI patients, the question arises whether lesion size parameters and predictive models based on those parameters are affected as well. In this retrospective observational study, the extent of the intramedullary lesion between individuals who sustained cervical and thoracolumbar SCI was compared, and its relation to clinical recovery was assessed. In total, 154 patients with subacute SCI (89 individuals with cervical lesions and 65 individuals with thoracolumbar lesions) underwent conventional clinical magnetic resonance imaging 1 month after injury and clinical examination at 1 and 12 months. The morphology of the focal lesion within the spinal cord was manually assessed on the midsagittal slice of T<sub>2</sub>-weighted magnetic resonance images and compared between cervical and thoracolumbar SCI patients, as well as between patients who improved at least one American Spinal Injury Association Impairment Scale (AIS) grade (converters) and patients without AIS grade improvement (nonconverters). The predictive value of lesion parameters including lesion length, lesion width, and preserved tissue bridges for predicting AIS grade conversion was assessed using regression models (conditional inference tree analysis). Lesion length was two times longer in thoracolumbar compared with cervical SCI patients (F = 39.48, <i>p</i> < 0.0001), whereas lesion width and tissue bridges width did not differ. When comparing AIS grade converters and nonconverters, converters showed a smaller lesion length (F = 5.46, <i>p</i> = 0.021), a smaller lesion width (F = 13.75, <i>p</i> = 0.0003), and greater tissue bridges (F = 12.87, <i>p</i> = 0.0005). Using regression models, tissue bridges allowed more refined subgrouping of patients in AIS groups B, C, and D according to individual recovery profiles between 1 month and 12 months after SCI, whereas lesion length added no additional information for further subgrouping. This study characterizes differences in the anteroposterior and craniocaudal lesion extents after SCI. The two times greater lesion length in thoracolumbar compared with cervical SCI might be related to differences in the anatomy, biomechanics, and perfusion between the cervical and thoracic spines. Preserved tissue bridges were less influenced by the lesion level while closely related to the clinical impairment. These results highlight the robustness and utility of tissue bridges as a neuroimaging biomarker for predicting the clinical outcome after SCI in heterogeneous patient populations and for patient stratification in clinical trials.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2146-2157"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603768","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}
Journal of neurotraumaPub Date : 2024-09-01Epub Date: 2024-07-03DOI: 10.1089/neu.2024.0168
Jotaro Tachino, Andreas K Demetriades, Wilco Peul, Shunichiro Nakao, Yusuke Katayama, Kenta Tanaka, Tetsuhisa Kitamura, Tomoya Hirose, Kosuke Kiyohara, Yutaka Umemura, Takeyuki Kiguchi, Masahiro Ojima, Kenichiro Ishida, Jun Oda
{"title":"Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.","authors":"Jotaro Tachino, Andreas K Demetriades, Wilco Peul, Shunichiro Nakao, Yusuke Katayama, Kenta Tanaka, Tetsuhisa Kitamura, Tomoya Hirose, Kosuke Kiyohara, Yutaka Umemura, Takeyuki Kiguchi, Masahiro Ojima, Kenichiro Ishida, Jun Oda","doi":"10.1089/neu.2024.0168","DOIUrl":"10.1089/neu.2024.0168","url":null,"abstract":"<p><p>Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2101-2113"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321006","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}
Journal of neurotraumaPub Date : 2024-09-01Epub Date: 2024-08-02DOI: 10.1089/neu.2024.0194
Brittany Grace Futch, Andreas Seas, Favour Ononogbu-Uche, Shahenda Khedr, Judah Kreinbrook, Christopher I Shaffrey, Theresa Williamson, James David Guest, Michael G Fehlings, Muhammad M Abd-El-Barr, Norah A Foster
{"title":"Shifting Trends in the Epidemiology of Cervical Spine Injuries: An Analysis of 11,822 Patients from the National Electronic Injury Surveillance System over Two Decades.","authors":"Brittany Grace Futch, Andreas Seas, Favour Ononogbu-Uche, Shahenda Khedr, Judah Kreinbrook, Christopher I Shaffrey, Theresa Williamson, James David Guest, Michael G Fehlings, Muhammad M Abd-El-Barr, Norah A Foster","doi":"10.1089/neu.2024.0194","DOIUrl":"10.1089/neu.2024.0194","url":null,"abstract":"<p><p>Cervical spine injuries (CSIs) are heterogeneous in nature and often lead to long-term disability and morbidity. However, there are few recent and comprehensive epidemiological studies on CSI. The objective of this study was to characterize recent trends in CSI patient demographics, incidence, etiology, and injury level. The National Electronic Injury Surveillance System was used to extract data on CSIs from 2002 to 2022. Weighted national estimates of CSI incidence were computed using yearly population estimates interpolated from U.S. census data. Data analysis involved extracting additional information from patient narratives to categorize injury etiology (i.e., fall) and identify CSI level. K-means clustering was performed on cervical levels to define upper versus lower cervical injuries. Appropriate summary statistics including mean with 95% confidence intervals and frequency were reported for age, sex, race, ethnicity, etiology, and disposition. Age between groups was compared using an independent weighted <i>Z</i>-test. All categorical variables were compared using Pearson chi-squared tests with Bonferroni correction for multiple comparisons. Ordinary least squares linear regression was used to quantify the rate of change of various metrics with time. A total of 11,822 patient records met the study criteria. The mean age of patients was 62.4 ± 22.7 years, 52.4% of whom were male and 61.4% of whom were White, 7.4% were Black, 27.8% were not specified, and the remaining comprised a variety of ethnicities. The most common mechanism of CSI was a fall (67.3%). There was a significant increase in the incidence of cervical injuries between 2003 and 2022 (<i>p</i> < 0.001). Unbiased K-means clustering defined upper cervical injuries as C1-C3 and lower cervical injuries as C4-C7. The mean age of patients with upper CSIs was 72.3 ± 19.6, significantly greater than the age of those with lower CSIs (57.1 ± 23.1, <i>p</i> < 0.001). Compared with lower CSI, White patients were more likely to have an upper CSI (67.4% vs. 73.7%; <i>p</i> < 0.001). While Black/African American (7.5% vs. 3.8%) and Hispanic (2.5% vs. 1.0%) patients were more likely to have a lower CSI (<i>p</i> < 0.001). Our study identified a significant increase in the incidence of CSIs over time, which was associated with increasing patient age. Our study detected a pragmatic demarcation of classifying upper injuries as C1-C3 and lower cervical injuries as C4-C7. Upper injuries were seen more often in older, White females who were treated and admitted, and lower injuries were seen more often in young, Black male patients who were released without admission.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"2158-2167"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748444","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}
Lara M Wittine, Jessica M Ketchum, Marc A Silva, Flora M Hammond, Joyce S Chung, Karina Loyo, Jose Lezama, Risa Nakase-Richardson
{"title":"Mortality Among Veterans Following Traumatic Brain Injury: A Veterans Administration Traumatic Brain Injury Model System Study.","authors":"Lara M Wittine, Jessica M Ketchum, Marc A Silva, Flora M Hammond, Joyce S Chung, Karina Loyo, Jose Lezama, Risa Nakase-Richardson","doi":"10.1089/neu.2024.0043","DOIUrl":"10.1089/neu.2024.0043","url":null,"abstract":"<p><p>Few studies have examined long-term mortality following traumatic brain injury (TBI) in a military population. This is a secondary analysis of a prospective, longitudinal study that examines long-term mortality (up to 10 years) post-TBI, including analyses of life expectancy, causes of death, and risk factors for death in service members and veterans (SM/V) who survived the acute TBI and inpatient rehabilitation. Among 922 participants in the study, the mortality rate was 8.3% following discharge from inpatient rehabilitation. The mean age of death was 54.5 years, with death occurring on average 3.2 years after injury, and with an average 7-year life expectancy reduction. SM/V with TBI were nearly four times more likely to die compared with the U.S. general population. Leading causes of death were external causes of injury, circulatory disease, and respiratory disorders. Also notable were deaths due to late effects of TBI itself and suicide. Falls were a significant mechanism of injury for those who died. Those who died were also more likely to be older at injury, unemployed, non-active duty status, not currently married, and had longer post-traumatic amnesia, longer rehabilitation stays, worse independence and disability scores at rehabilitation discharge, and a history of mental health issues before injury. These findings indicate that higher disability and less social supportive infrastructure are associated with higher mortality. Our investigation into the vulnerabilities underlying premature mortality and into the major causes of death may help target future prevention, surveillance, and monitoring interventions.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498282","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}
James P Barrett, Taryn G Aubrecht, Aidan Smith, Maria Vaida, Rebecca J Henry, Sarah J Doran, Alan I Faden, Bogdan A Stoica
{"title":"Molecular Pathway Changes Associated with Different Post-Conditioning Exercise Interventions After Experimental TBI.","authors":"James P Barrett, Taryn G Aubrecht, Aidan Smith, Maria Vaida, Rebecca J Henry, Sarah J Doran, Alan I Faden, Bogdan A Stoica","doi":"10.1089/neu.2024.0120","DOIUrl":"10.1089/neu.2024.0120","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) causes complex, time-dependent molecular and cellular responses, which include adaptive changes that promote repair and recovery, as well as maladaptive processes such as chronic inflammation that contribute to chronic neurodegeneration and neurological dysfunction. Hormesis is a well-established biological phenomenon in which exposure to low-dose toxins or stressors results in protective responses to subsequent higher-level stressors or insults. Hormetic stimuli show a characteristic U-shaped or inverted J-shaped dose-response curve, as well as being time and exposure-frequency dependent, similar to pre-conditioning and post-conditioning actions. Voluntary exercise interventions, before or after injury, appear to follow these general hormetic principles. But the molecular alterations associated with exercise interventions or more general hormetic responses have received only limited attention. In this study, we used a well-characterized mouse TBI model to assess the effects of different post-conditioning exercise-intervention paradigms on diverse molecular pathways, including neuroinflammation regulators, and post-traumatic neurological deficits. We generated high-throughput gene expression data and associated molecular pathway analyses to assess the potential molecular mechanisms associated with time- and duration-dependent voluntary exercise intervention, as well as time after treatment. Importantly, we also used newer analytical methods to more broadly assess the impact of exercise on diverse molecular pathways. TBI caused long-term changes in multiple neuroinflammation markers and chronic cognitive dysfunction. Notably, all delayed, post-conditioning exercise interventions reduced post-traumatic neuroinflammation and/or attenuated the related cognitive changes, albeit with different pathway specificity and effects magnitude. Exercise comprehensively reversed injury-associated effects in the hippocampus across both activated inflammatory and inhibited neuronal pathways, consistent with a return toward the noninjured, homeostatic state. In contrast, the cortex showed a less consistent pattern with more limited attenuation of inflammatory pathway activation and an amplification in the injury-dependent inhibition of select noninflammatory pathways, indicating less effective and potentially detrimental responses to exercise. Exercise intervention beginning 2 weeks after injury and lasting 2 weeks was less effective than exercise continuing for 4 weeks. Exercise initiated at a more delayed timepoint of 6 weeks after injury and continuing for 4 weeks was more effective than that during the acute phase. The delayed paradigm was also more effective than exercise initiated at 10 weeks after injury and continuing for 8 weeks, consistent with hormetic responses in other models and species. Overall, our study delineates regional and interventional parameters, as well as related molecular pathway changes, associated with","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792655","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}
Melissa G Papini, André N Avila, Melinda Fitzgerald, Sarah C Hellewell
{"title":"Evidence for Altered White Matter Organization After Mild Traumatic Brain Injury: A Scoping Review on the Use of Diffusion Magnetic Resonance Imaging and Blood-Based Biomarkers to Investigate Acute Pathology and Relationship to Persistent Post-Concussion Symptoms.","authors":"Melissa G Papini, André N Avila, Melinda Fitzgerald, Sarah C Hellewell","doi":"10.1089/neu.2024.0039","DOIUrl":"10.1089/neu.2024.0039","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurological and cognitive deficits experienced post-mTBI. Evidence suggests that diffusion magnetic resonance imaging (dMRI) and blood-based biomarkers could be used as surrogate markers of WM organization. We conducted a scoping review according to PRISMA-ScR guidelines, aiming to collate evidence for the use of dMRI and/or blood-based biomarkers of WM organization, in mTBI and PPCS, and document relationships between WM biomarkers and symptoms. We focused specifically on biomarkers of axonal or myelin integrity post-mTBI. Biomarkers excluded from this review therefore included the following: astroglial, perivascular, endothelial, and inflammatory markers. A literature search performed across four databases, EMBASE, Scopus, Google Scholar, and ProQuest, identified 100 records: 68 analyzed dMRI, 28 assessed blood-based biomarkers, and 4 used both. Blood biomarker studies commonly assessed axonal cytoskeleton proteins (i.e., tau); dMRI studies assessed measures of WM organization (i.e., fractional anisotropy). Significant biomarker alterations were frequently associated with heightened symptom burden and prolonged recovery time post-injury. These data suggest that dMRI and blood-based biomarkers may be useful proxies of WM organization, although few studies assessed these complementary measures in parallel, and the relationship between modalities remains unclear. Further studies are warranted to assess the benefit of a combined biomarker approach in evaluating alterations to WM organization after mTBI.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878896","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":"Hepatocyte Growth Factor Delivery to Injured Cervical Spinal Cord Using an Engineered Biomaterial Protects Respiratory Neural Circuitry and Preserves Functional Diaphragm Innervation.","authors":"Samantha J Thomas, Biswarup Ghosh, Zhicheng Wang, Mengxi Yang, Jia Nong, Jenna Severa, Megan C Wright, Yinghui Zhong, Angelo C Lepore","doi":"10.1089/neu.2024.0084","DOIUrl":"10.1089/neu.2024.0084","url":null,"abstract":"<p><p>A major portion of spinal cord injury (SCI) cases occur in the cervical region, where essential components of the respiratory neural circuitry are located. Phrenic motor neurons (PhMNs) housed at cervical spinal cord level C3-C5 directly innervate the diaphragm, and SCI-induced damage to these cells severely impairs respiratory function. In this study, we tested a biomaterial-based approach aimed at preserving this critical phrenic motor circuitry after cervical SCI by locally delivering hepatocyte growth factor (HGF). HGF is a potent mitogen that promotes survival, proliferation, migration, repair, and regeneration of a number of different cell and tissue types in response to injury. We developed a hydrogel-based HGF delivery system that can be injected into the intrathecal space for local delivery of high levels of HGF without damaging the spinal cord. Implantation of HGF hydrogel after unilateral C5 contusion-type SCI in rats preserved diaphragm function, as assessed by <i>in vivo</i> recordings of both compound muscle action potentials and inspiratory electromyography amplitudes. HGF hydrogel also preserved PhMN innervation of the diaphragm, as assessed by both retrograde PhMN tracing and detailed neuromuscular junction morphological analysis. Furthermore, HGF hydrogel significantly decreased lesion size and degeneration of cervical motor neuron cell bodies, as well as reduced levels surrounding the injury site of scar-associated chondroitin sulfate proteoglycan molecules that limit axon growth capacity. Our findings demonstrate that local biomaterial-based delivery of HGF hydrogel to injured cervical spinal cord is an effective strategy for preserving respiratory circuitry and diaphragm function.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792683","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":"Meningeal Damage and Interface Astroglial Scarring in the Rat Brain Exposed to a Laser-Induced Shock Wave(s).","authors":"Satoko Kawauchi, Akemi Kono, Yuriko Muramatsu, Grant Hennes, Shuta Seki, Susumu Tominaga, Yasue Haruyama, Yukari Komuta, Izumi Nishidate, Susumu Matsukuma, Yushan Wang, Shunichi Sato","doi":"10.1089/neu.2023.0572","DOIUrl":"10.1089/neu.2023.0572","url":null,"abstract":"<p><p>In the past decade, signature clinical neuropathology of blast-induced traumatic brain injury has been under intense debate, but interface astroglial scarring (IAS) seems to be convincing. In this study, we examined whether IAS could be replicated in the rat brain exposed to a laser-induced shock wave(s) (LISW[s]), a tool that can produce a pure shock wave (primary mechanism) without dynamic pressure (tertiary mechanism). Under certain conditions, we observed astroglial scarring in the subpial glial plate (SGP), gray-white matter junctions (GM-WM), ventricular wall (VW), and regions surrounding cortical blood vessels, accurately reproducing clinical IAS. We also observed shock wave impulse-dependent meningeal damage (dural microhemorrhage) <i>in vivo</i> by transcranial near-infrared (NIR) reflectance imaging. Importantly, there were significant correlations between the degree of dural microhemorrhage and the extent of astroglial scarring more than 7 days post-exposure, suggesting an association of meningeal damage with astroglial scarring. The results demonstrated that the primary mechanism alone caused the IAS and meningeal damage, both of which are attributable to acoustic impedance mismatching at multi-layered tissue boundaries. The time course of glial fibrillary acidic protein (GFAP) immunoreactivity depended not only on the LISW conditions but also on the regions. In the SGP, significant increases in GFAP immunoreactivity were observed at 3 days post-exposure, whereas in the GM-WM and VW, GFAP immunoreactivity was not significantly increased before 28 days post-exposure, suggesting different pathological mechanisms. With the high-impulse single exposure or the multiple exposure (low impulse), fibrotic reaction or fibrotic scar formation was observed, in addition to astroglial scarring, in the cortical surface region. Although there are some limitations, this seems to be the first report on the shock-wave-induced IAS rodent model. The model may be useful to explore potential therapeutic approaches for IAS.</p>","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e2039-e2053"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293771","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}
Journal of neurotraumaPub Date : 2024-08-01Epub Date: 2024-05-02DOI: 10.1089/neu.2023.0475
Douglas P Terry, Jacob Jo, Kristen L Williams, Bruce A Maxwell, Paul D Berkner, Grant L Iverson, Scott L Zuckerman
{"title":"Recovery After Sport-Related Concussion in Collegiate Athletes With Self-Reported Pre-Injury Migraines.","authors":"Douglas P Terry, Jacob Jo, Kristen L Williams, Bruce A Maxwell, Paul D Berkner, Grant L Iverson, Scott L Zuckerman","doi":"10.1089/neu.2023.0475","DOIUrl":"10.1089/neu.2023.0475","url":null,"abstract":"<p><p>Pre-injury migraines might be a risk factor for prolonged recovery after sport-related concussion (SRC). We sought to examine whether a pre-injury history of migraines is associated with worse recovery following SRC in collegiate athletes. Data were collected through a prospective concussion surveillance system in 11 National Collegiate Athletic Association (NCAA) Division III college athletic programs between September 2014 and March 2020. Our primary independent variable, pre-injury migraines, were self-reported by the athletes. Between those with and without migraines, the outcomes of days to return-to-learn (RTL) without academic accommodations and return-to-play (RTP) were compared using Mann-Whitney <i>U</i> tests. Each athlete's RTL and RTP status was dichotomized (i.e., returned vs. not returned) at various time points for RTL (i.e., 7/14/21/28 days) and RTP (i.e., 14/21/28/56 days). Chi-squared tests were performed to compare the proportions of RTL and RTP status between groups. Multivariable regressions analyzed potential predictors of RTL and RTP adjusting for age, gender, prior concussions, other health conditions, and symptom severity. Of 1409 athletes with an SRC, 111 (7.9%) had a pre-injury history of migraines. Compared with those without migraines, those with migraines had longer median (interquartile range [IQR]) days to RTL (migraines = 7.0 [3.0-12.3] vs. no migraines = 5.0 [2.0-10.0], <i>U</i> = 53,590.5, <i>p</i> = 0.022). No differences were found in RTP between the two groups (migraines = 16.0 [10.0-33.0] vs. nχo migraines 15.0 [11.0-23.0], <i>U</i> = 38,545.0, <i>p</i> = 0.408). Regarding RTL, significantly lower proportions of athletes in the migraine group had fully RTL, without accommodations, at ≤14 days (77.5% vs. 85.2%, χ<sup>2</sup> = 4.33, <i>p</i> = 0.037), ≤21 days (85.3% vs. 93.0%, χ<sup>2</sup> = 7.99, <i>p</i> = 0.005), and ≤28 days (88.2% vs. 95.6%, χ<sup>2</sup> = 10.60, <i>p</i> = 0.001). Regarding RTP, a significantly lower proportion of athletes in the migraine group RTP at ≤28 days (72.0% vs. 82.7%, χ<sup>2</sup> = 5.40, <i>p</i> = 0.020) and ≤56 days (84.0% vs. 93.0%, χ<sup>2</sup> = 8.19, <i>p</i> = 0.004). In a multivariable model predicting RTL that was adjusted for age, gender, acute concussion symptoms, and other health variables (e.g., attention-deficit/hyperactivity disorder [ADHD], history of mental health difficulties), pre-injury history of migraine was associated with longer RTL (β = 0.06, <i>p</i> = 0.030). In a multivariable model predicting RTP, pre-injury history of migraine was not associated with RTP (β = 0.04, <i>p</i> = 0.192). In collegiate athletes, pre-injury migraine history was independently associated with longer RTL but not RTP. When comparing the proportions of those with successful RTP by days, significantly lower proportions of those with migraines showed successful RTP at ≤28 days and ≤56 days. Futures studies should study the generalizability of our findings in other","PeriodicalId":16512,"journal":{"name":"Journal of neurotrauma","volume":" ","pages":"e1986-e1995"},"PeriodicalIF":3.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184685","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}