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Congenital hearing loss affects one in 500 newborns. Sequence variations in OTOF, which encodes the calcium-binding protein otoferlin, are responsible for 1-8% of congenital, nonsyndromic hearing loss and are the leading cause of auditory neuropathy spectrum disorders. The natural history of otoferlin-related hearing loss, the relationship between OTOF genotype and hearing loss phenotype, and the outcomes of clinical practices in patients with this genetic disorder are incompletely understood because most analyses have reported on small numbers of cases with homogeneous OTOF genotypes. Here, we present the first systematic, quantitative literature review of otoferlin-related hearing loss, which analyzes patient-specific data from 422 individuals across 61 publications. While most patients display a typical phenotype of severe-to-profound hearing loss with prelingual onset, 10-15% of patients display atypical phenotypes, including mild-to-moderate, progressive, and temperature-sensitive hearing loss. Patients' phenotypic presentations appear to depend on their specific genotypes. For example, non-truncating variants located in and immediately downstream of the C2E calcium-binding domain are more likely to produce atypical phenotypes. Additionally, the prevalence of certain sequence variants and their associated phenotypes varies between populations due to evolutionary founder effects. Our analyses also suggest otoacoustic emissions are less common in older patients and those with two truncating OTOF variants. Critically, our review has implications for the application and limitations of clinical practices, including newborn hearing screenings, hearing aid trials, cochlear implants, and upcoming gene therapy clinical trials. We conclude by discussing the limitations of available research and recommendations for future studies on this genetic cause of hearing loss.
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Sordera , Pérdida Auditiva Central , Pérdida Auditiva , Recién Nacido , Humanos , Anciano , Pérdida Auditiva/genética , Genotipo , FenotipoRESUMEN
Riluzole is the only treatment known to improve survival in patients with Amyotrophic Lateral Sclerosis (ALS). However, oral riluzole efficacy is modest at best, further it is known to have large inter-individual variability of serum concentration and clearance, is formulated as an oral drug in a patient population plagued with dysphagia, and has known systemic side-effects like asthenia (limiting patient compliance) and elevated liver enzymes. In this context, we postulated that continuous intrathecal (IT) infusion of low doses of riluzole could provide consistent elevations of the drug spinal cord (SC) concentrations at or above those achieved with oral dosing, without increasing the risk for adverse events associated with systemic drug exposure or off-target side effects in the brain. We developed a formulation of riluzole for IT delivery and conducted our studies in purpose-bred hound dogs. Our non-GLP studies revealed that IT infusion alone was able to increase SC concentrations above those provided by oral administration, without increasing plasma concentrations. We then conducted two GLP studies that combined IT infusion with oral administration at human equivalent dose, to evaluate SC and brain concentrations of riluzole along with assessments of safety and tolerability. In the 6-week study, the highest IT dose (0.2 mg/hr) was well tolerated by the animals and increased SC concentrations above those achieved with oral riluzole alone, without increasing brain concentrations. In the 6-month study, the highest dose tested (0.4 mg/hr) was not tolerated and yielded SC significantly above those achieved in all previous studies. Our data show the feasibility and safety profile of continuous IT riluzole delivery to the spinal cord, without concurrent elevated liver enzymes, and minimal brain concentrations creating another potential therapeutic route of delivery to be used in isolation or in combination with other therapeutics."
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Esclerosis Amiotrófica Lateral , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Animales , Perros , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Riluzol/uso terapéutico , Encéfalo , Administración OralRESUMEN
BACKGROUND: Occipital neuralgia (ON) is defined as paroxysmal pain in the distribution of the greater, lesser, and/or third occipital nerves. ON can be refractory to conservative management and minimally invasive interventions. Neuromodulatory procedures can potentially treat refractory ON and include occipital nerve stimulation and the sparsely reported high cervical spinal cord stimulation (SCS). OBJECTIVE: To report our experience and conduct a systematic literature review of studies evaluating the effect of high cervical SCS as a treatment modality for refractory ON. METHODS: A retrospective review of patients with refractory ON who underwent high cervical SCS was conducted. In addition, a systematic literature review was performed according to the PRISMA guidelines. RESULTS: Five patients with refractory ON were treated with high cervical (C1-C3) SCS in our institution. Two out of five (40%) patients reported a successful trial stimulation (>50% pain reduction) and received permanent implantation. During the follow-up, the visual analog scale score decreased from 7.5 to 4 and from 6.5 to 5 in these patients. No complications were reported for any of the patients. The systematic literature review, identified two eligible studies, comprising 18 patients overall who underwent cervicomedullary junction SCS. Nine out of 18 patients (50%) had a successful trial and received permanent implantation. CONCLUSION: High cervical or cervicomedullary junction SCS is associated with a 40-50% successful trial rate in refractory ON. No major complications were noted during the follow-up. Future studies are needed to compare the different neurosurgical options, in order to identify the optimal treatment strategy for refractory ON.
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BACKGROUND: Persistent idiopathic facial pain (PIFP) can be refractory to conventional management approaches. Neuromodulatory procedures such as percutaneous trigeminal nerve stimulation (TNS) have been sparsely reported as potential treatment options for amelioration of debilitating refractory pain associated with PIFP. The present study investigated the use of percutaneous TNS in a series of patients with PIFP to evaluate the potential efficacy of pain relief. METHODS: We performed a retrospective medical record review for patients with PIFP who had presented to Emory University Hospital and had undergone TNS for PIFP. The primary outcomes were postoperative pain using the visual analog scale (VAS) for pain and morphine equivalent use. Descriptive statistics, mean ± standard deviation, and the nonparametric Wilcoxon sign rank test were used, as appropriate. A P value of <0.05 was considered statistically significant. RESULTS: A total of 23 patients underwent percutaneous TNS for PIFP. Of the 23 patients, 20 (86.9%) reported a >50% improvement after trial stimulation. Of the patients who had received permanent TNS implants, 13 of 17 (76.4%) had VAS scores available. For these patients, the mean preoperative VAS score had decreased from 5.69 ± 2.09 to 0.15 ± 0.55 postoperatively. The VAS scores displayed a statistically significant decrease after TNS (P = 0.0014). A subset of 9 patients with available data also demonstrated a significant reduction in morphine equivalent use after TNS (before, 50.54 ± 51.30; after, 25.83 ± 33.58; P = 0.048). CONCLUSION: The results from the present study have indicated that percutaneous stimulation of the trigeminal nerve is efficacious in the treatment of PIFP and can significantly decrease morphine equivalent use. Further longitudinal studies are required to validate our results.
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Terapia por Estimulación Eléctrica/métodos , Dolor Facial/terapia , Manejo del Dolor/métodos , Neuralgia del Trigémino/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Nervio Trigémino/fisiologíaRESUMEN
BACKGROUND: Patients with refractory chronic primary headache disorders have extremely debilitating symptoms, severe comorbidities (e.g., anxiety, depression), and a significant reduction in quality of life. The headaches are extremely difficult to treat, as they are often refractory to pharmacologic and procedural interventions. Neuromodulation with stimulation of the occipital and supraorbital nerves has been proposed as a viable treatment for these refractory headaches. We retrospectively review the long-term (33.5 ± 20 months) results of supraorbital occipital nerve circumferential stimulation (SOCS) in patients with chronic primary headache disorders. METHODS: We retrospectively review 25 patients who were evaluated for SOCS for chronic primary headache disorders from 2010 to 2017 at a single institution with a single neurosurgeon. RESULTS: Of these 25 patients, 14 saw benefits to their trial stage of stimulation and underwent full implantation. A total 3 patients were excluded from further analysis because of having <2 months of follow-up or discordant data. Of the 11 patients analyzed, there was an overall response rate (≥50% pain reduction) of 82%. The average preoperative 10-point pain score dropped from 7.1 ± 1.6 to a postoperative score of 3.3 ± 2.1. However, there was a high rate of complications including infection, erosion, and loss of effect. CONCLUSIONS: The results (82% response) suggest that SOCS may be an effective treatment and should be studied more extensively. Occipital nerve stimulation alone has shown 40% to 50% response rate in published studies. However, the relatively high complication rate highlights an obstacle for the approach for the treatment of refractory headache disorders and room for device optimization.
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BACKGROUND: There is a growing literature of evidence that the use of acellular dermal matrices (ADMs) in abdominal wall reconstruction (AWR) for high-risk patients provides superior complication profiles when compared with standard synthetic mesh. Here we compare Fortiva, Strattice, and Alloderm ADMs in AWR. METHODS: In a prospectively maintained database, all patients undergoing AWR between January 2003 and November 2016 were reviewed. Hernia recurrence and surgical site occurrence (SSO) were our primary and secondary endpoints. Kaplan-Meier survival curves and logistic regression models were used to evaluate risks for hernia recurrence and SSO. RESULTS: A total of 229 patients underwent AWR with 1 of 3 ADMs. Median follow-up time was 20.9 months (1-60 months). Cumulative recurrence rates for each mesh were 6.9%, 11.2%, and 22.0% (P = 0.04), for Fortiva, Strattice, and Alloderm groups. Surgical site occurrence for each mesh was 56.9%, 49.0%, and 49.2%, respectively. Seroma was significantly lower in the Fortiva group (1.4%; P = 0.02). Independent risk factors hernia recurrence included body mass index of 30 kg/m(2) or higher and hypertension. Adjusted risk factors included oncologic resection for hernia recurrence (odds ratio, 5.3; confidence interval, 1.1-97.7; P = 0.11) and a wound class of contaminated or dirty/infected for SSO (odds ratio, 3.6; confidence interval, 1.0-16.6; P = 0.07). CONCLUSIONS: Acellular dermal matrices provide a durable repair with low overall rate of recurrence and complications in AWR. The recurrence and complication profiles differ between brands. With proper patient selection and consideration, ADMs can be used confidently for a variety of indications and wound classifications.
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Pared Abdominal/cirugía , Dermis Acelular/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Mallas Quirúrgicas/efectos adversos , Cicatrización de Heridas/fisiología , Pared Abdominal/fisiopatología , Técnicas de Cierre de Herida Abdominal , Adulto , Anciano , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Hernia Ventral/diagnóstico , Hernia Ventral/cirugía , Herniorrafia/efectos adversos , Herniorrafia/métodos , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/cirugía , Valor Predictivo de las Pruebas , Puntaje de Propensión , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Trigeminal ganglion stimulation can be effective for trigeminal neuralgia. For patients who respond well to neurostimulation delivered percutaneously through the foramen ovale but require extensive revision and removal of instrumentation, a subtemporal approach for stimulation of the trigeminal ganglion is an alternative option as a salvage procedure. CASE DESCRIPTION: We report on a 47-year-old woman who responded well to neurostimulation for trigeminal neuropathic pain over a 1-year period from 2008 to 2009. Her preoperative pain on the numerical rating scale (NRS) was between 7 and 8 out of 10, which decreased to 2 out of 10 postoperatively. However, she developed lead migration because of a motor vehicle accident. After revision surgeries to correct this, she continued to experience pain relief until 2011. At follow-up, signs of infection prompted removal of instrumentation and subsequent return of her pain. She continued to experience persistent and severe pain (NRS score 7 of 10), which was intractable to pharmacologic treatment over 5 years. She returned in 2016 to discuss neurosurgical options, and the original approach was ruled out because of her history of lead migration, erosion, and scarring. A subtemporal approach was pursued as a salvage option, which provided several advantages for this patient. CONCLUSIONS: The subtemporal approach for salvage placement of the trigeminal ganglion stimulating electrode was effective in this patient and minimized risks given her history of erosion and multiple operations. This suggests that the subtemporal approach is a viable salvage operation for trigeminal ganglion stimulation for trigeminal neuropathic pain.
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Terapia por Estimulación Eléctrica/instrumentación , Electrodos Implantados , Neuralgia del Trigémino/terapia , Terapia por Estimulación Eléctrica/métodos , Femenino , Humanos , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/métodos , Dolor Intratable/terapia , Terapia Recuperativa/instrumentación , Terapia Recuperativa/métodos , Ganglio del Trigémino/cirugíaRESUMEN
BACKGROUND: Occipital neuralgia is a chronic pain syndrome characterized by sharp, shooting pains in the distribution of the occipital nerves. Although relatively rare, it associated with extremely debilitating symptoms that drastically affect a patient's quality of life. Furthermore, it is extremely difficult to treat as the symptoms are refractory to traditional treatments, including pharmacologic and procedural interventions. A few previous case studies have established the use of a neurostimulation of the occipital nerves to treat occipital neuralgia. OBJECTIVE: The following expands on that literature by retrospectively reviewing the results of occipital nerve stimulation in a relatively large patient cohort (29 patients). METHODS: A retrospective review of 29 patients undergoing occipital nerve stimulation for occipital neuralgia from 2012 to 2017 at a single institution with a single neurosurgeon. RESULTS: Of those 29 patients, 5 were repair or replacement of previous systems, 4 did not have benefit from trial stimulation, and 20 saw benefit to their trial stage of stimulation and went on to full implantation. Of those 20 patients, even with a history of failed procedures and pharmacological therapies, there was an overall success rate of 85%. The average preoperative 10-point pain score dropped from 7.4 ± 1.7 to a postoperative score of 2.9 ± 1.7. However, as with any peripheral nerve stimulation procedure, there were complications (4 patients), including infection, hardware erosion, loss of effect, and lead migration, which required revision or system removal. CONCLUSION: Despite complications, the results suggest, overall, that occipital nerve stimulation is a safe and effective procedure for refractory occipital neuralgia and should be in the neurosurgical repertoire for occipital neuralgia treatment.
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Dolor Crónico/terapia , Terapia por Estimulación Eléctrica/métodos , Neuralgia/terapia , Manejo del Dolor/métodos , Nervios Espinales , Adulto , Dolor Crónico/diagnóstico por imagen , Estudios de Cohortes , Terapia por Estimulación Eléctrica/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/diagnóstico por imagen , Manejo del Dolor/instrumentación , Estudios Retrospectivos , Nervios Espinales/diagnóstico por imagen , Estimulación Eléctrica Transcutánea del Nervio/instrumentación , Estimulación Eléctrica Transcutánea del Nervio/métodos , Resultado del TratamientoRESUMEN
Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* susceptibility weighted images. ARIA in general has been linked to the presence of amyloid-ß (Aß)-type cerebral amyloid angiopathy, an accumulation of misfolded Aß protein in the vascular wall that impairs the integrity of brain blood vessels. However, the pathobiology of ARIA remains poorly understood, in part due to the absence of an animal model of the disorder that would enable a contemporaneous analysis of tissue integrity in the affected region. Here we describe both ARIA-E and ARIA-H in an aged squirrel monkey (Saimiri sciureus), a nonhuman primate model of naturally occurring cerebral amyloid angiopathy. Histopathologic examination of the anomalous region revealed reactive astrocytosis and microgliosis, infiltration of systemic inflammatory/immune cells, damage to axons and myelin, and hemosiderin deposition. The disruption of axons in particular suggests that ARIA-E could have functional consequences for affected regions. The squirrel monkey model can be useful for studying the pathogenesis and long-term effects of ARIA, and for testing the safety and efficacy of emerging therapies for Alzheimer's disease.
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Péptidos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/metabolismo , Animales , Encéfalo/patología , Angiopatía Amiloide Cerebral/patología , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Femenino , Gliosis/diagnóstico por imagen , Gliosis/metabolismo , Gliosis/patología , Inmunohistoquímica , Imagen por Resonancia Magnética , SaimiriRESUMEN
BACKGROUND: Acellular dermal matrices (ADM) are now routine in postmastectomy prosthetic-based breast reconstruction. The goal of the current study was to compare the complications of 2 ADM products-AlloDerm and Cortiva. METHODS: A retrospective analysis of prosthetic-based breast reconstruction in Atlanta, Ga., over 5 years. Inclusion criteria were the use of the ADM types (AlloDerm or Cortiva) and use of a tissue expander or implant. Statistical analysis compared group demographics, risk factors, and early complications. RESULTS: Of the 298 breast reconstructions, 174 (58.4%) used AlloDerm and 124 (41.6%) used Cortiva. There was no difference in overall complication frequency (16 AlloDerm and 18 Cortiva; P = 0.195). Within specific categories, there was a difference in mastectomy skin flap necrosis, but, based on further regression analysis, this was attributable to differences in body mass index (P = 0.036). Furthermore, there were no differences in the rates of infection (6 AlloDerm and 5 Cortiva; P = 1.0), seroma/hematoma (9 AlloDerm and 7 Cortiva; P = 1.0), or drain duration (13.2 day AlloDerm and 14.2 day Cortiva, P = 0.2). By using a general estimating equation for binomial logistical regression, it was found that only current tobacco use (P = 0.033) was a significant predictor for a complication. Trending predictors were body mass index (P = 0.074) and age (P = 0.093). The type of matrix was not a significant predictor for any of the recorded complication (P = 0.160). CONCLUSIONS: Although AlloDerm is well established, we have shown that Cortiva has an equivalent complication frequency. Future work will focus on long-term outcome measures and histological evaluation of vascularization and integration.
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The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively.
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Aprendizaje por Asociación , Núcleo Amigdalino Central/fisiología , Miedo , Animales , Conducta Animal , Núcleo Amigdalino Central/metabolismo , Condicionamiento Psicológico , Humanos , Memoria , Vías Nerviosas/fisiología , Plasticidad Neuronal , Neuropéptidos/metabolismoRESUMEN
Understanding the function and connectivity of thalamic nuclei is critical for understanding normal and pathological brain function. The medial geniculate nucleus (MGN) has been studied mostly in the context of auditory processing and its connection to the auditory cortex. However, there is a growing body of evidence that the MGN and surrounding associated areas ('MGN/S') have a diversity of projections including those to the globus pallidus, caudate/putamen, amygdala, hypothalamus, and thalamus. Concomitantly, pathways projecting to the medial geniculate include not only the inferior colliculus but also the auditory cortex, insula, cerebellum, and globus pallidus. Here we expand our understanding of the connectivity of the MGN/S by using comparative diffusion weighted imaging with probabilistic tractography in both human and mouse brains (most previous work was in rats). In doing so, we provide the first report that attempts to match probabilistic tractography results between human and mice. Additionally, we provide anterograde tracing results for the mouse brain, which corroborate the probabilistic tractography findings. Overall, the study provides evidence for the homology of MGN/S patterns of connectivity across species for understanding translational approaches to thalamic connectivity and function. Further, it points to the utility of DTI in both human studies and small animal modeling, and it suggests potential roles of these connections in human cognition, behavior, and disease.
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Cuerpos Geniculados/citología , Vías Nerviosas/citología , Adulto , Animales , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Adulto JovenRESUMEN
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is usually fatal within 2-5years. Unfortunately, the only treatment currently available is riluzole, which has a limited efficacy. As a redress, there is an expanding literature focusing on other potential treatments. One such potential treatment option utilizes the vascular endothelial growth factor (VEGF) family, which includes factors that are primarily associated with angiogenesis but are now increasingly recognized to have neurotrophic effects. Reduced expression of a member of this family, VEGF-A, in mice results in neurodegeneration similar to that of ALS, while treatment of animal models of ALS with either VEGF-A gene therapy or VEGF-A protein has yielded positive therapeutic outcomes. These basic research findings raise the potential for a VEGF therapy to be translated to the clinic for the treatment of ALS. This review covers the VEGF family, its receptors and neurotrophic effects as well as VEGF therapy in animal models of ALS and advances towards clinical trials.
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Esclerosis Amiotrófica Lateral/terapia , Terapia Genética/métodos , Factor A de Crecimiento Endotelial Vascular/genética , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Diseño de Fármacos , Regulación de la Expresión Génica , Humanos , Ratones , Proteínas/farmacología , Proteínas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
As the power of studying mouse genetics and behavior advances, research tools to examine systems level connectivity in the mouse are critically needed. In this study, we compared statistical mapping of the olfactory system in adult mice using manganese-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI) with probabilistic tractography. The primary goal was to determine whether these complementary techniques can determine mouse olfactory bulb (OB) connectivity consistent with known anatomical connections. For MEMRI, 3D T1-weighted images were acquired before and after bilateral nasal administration of MnCl(2) solution. Concomitantly, high-resolution diffusion-tensor images were obtained ex vivo from a second group of mice and processed with a probabilistic tractography algorithm originating in the OB. Incidence maps were created by co-registering and overlaying data from the two scan modalities. The resulting maps clearly show pathways between the OB and amygdala, piriform cortex, caudate putamen, and olfactory cortex in both the DTI and MEMRI techniques that are consistent with the known anatomical connections. These data demonstrate that MEMRI and DTI are complementary, high-resolution neuroimaging tools that can be applied to mouse genetic models of olfactory and limbic system connectivity.
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Mapeo Encefálico/métodos , Cloruros , Medios de Contraste , Imagen de Difusión Tensora , Imagen por Resonancia Magnética/métodos , Compuestos de Manganeso , Vías Olfatorias/citología , Algoritmos , Animales , Procesamiento de Imagen Asistido por Computador , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Modelos Estadísticos , Vías Nerviosas/citología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: High throughput, brain-wide analysis of neural circuit connectivity is needed to understand brain function across species. Combining such tractography techniques with small animal models will allow more rapid integration of systems neuroscience with molecular genetic, behavioral, and cellular approaches. METHODS: We collected DTI and T2 scans on 3 series of 6 fixed mouse brains ex vivo in a 9.4 Tesla magnet. The DTI analysis of ten mouse brains focused on comparing prelimbic (PL) and Infralimbic (IL) probabilistic tractography. To validate the DTI results a preliminary set of 24 additional mice were injected with BDA into the IL and PL. The DTI results and preliminary BDA results were also compared to previously published rat connectivity. RESULTS: We focused our analyses on the connectivity of the mouse prelimbic (PL) vs. infralimbic (IL) cortices. We demonstrated that this DTI analysis is consistent across scanned mice, with prior analyses of rat IL/PL connectivity, and with mouse PL and IL projections using the BDA tracer. CONCLUSIONS: High-throughput ex vivo DTI imaging in the mouse delineated both common and differential connectivity of the IL and PL cortex. The scanning methodology provided a balance of tissue contrast, signal-to-noise ratio, resolution and throughput. Our results are largely consistent with previously published anterograde staining techniques in rats, and the preliminary tracer study of the mouse IL and PL provided here.
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Encéfalo/anatomía & histología , Imagen de Difusión Tensora/métodos , Vías Nerviosas/anatomía & histología , Animales , Ensayos Analíticos de Alto Rendimiento , Procesamiento de Imagen Asistido por Computador , Ratones , Ratones Endogámicos C57BLRESUMEN
Injury-producing mechanisms associated with rear-end impact collision has remained a mystery not withstanding numerous investigations devoted to its scrutiny. Several criteria have been proposed to predict the injury-causing mechanism, but none have been universally accepted. The challenge lies in determining a set of testing procedures representative of real-world collisions, wherein the results obtained are not only the same as human testing, but remain consistent with various subjects and impact conditions. It is hypothesized that one of the most important considerations in the testing methodology is the effect of initial seated position (ISP) on occupant kinematics during a rear impact collision. This study involves two parts that evaluates the effects of ISP during rear-end impact. In the first part, head acceleration results of computer simulation using Hybrid III TNO rear impact dummy (TRID) are compared to physical impact testing (PIT) of humans. The second part focuses on the computer simulation using TRID to obtain different neck parameters such as NIC (Neck Injury Criterion), NIJ (Neck Injury Predictor), neck forces and moments to predict the level of neck injury such as whiplash associated disorder (WAD) during low speed rear-end impact. In PIT, a total of 17 rear-impact tests were conducted with a nominal 8-km/hour change in velocity to 5 subjects in four different seated positions comprising of a normal position (NP) and three out of positions (OOP). The first position was a NP, defined as torso against the seat back, looking straight ahead, hands on the steering wheel, and feet on the floor. The second position was a head flex position (HFP), defined as the normal position with head flexed forward approximately 20 degrees. The third position was a torso lean position (TLP), defined as the normal position with torso leaned forward approximately 10 degrees away from the seat back. Lastly, a torso lean head flex position (TLHFP), defined as the normal position with the head flexed forward approximately 20 degrees and torso leaned forward approximately 10 degrees. The head acceleration plots from PIT reveal that for the third and fourth positions (TLP and TLHFP) when the subject torso leaned forward, the peak head acceleration for the subject decreased and there was also a delay in reaching the peak. The Hybrid III-TRID anthropomorphic test dummy (ATD) was used in the same four different seated positions using computer simulation software MAthematical DYnamic MOdel (MADYMO 6.0) and the head acceleration results were compared to PIT. The comparison demonstrates that the Hybrid III-TRID ATD with MADYMO can be a reliable testing procedure during low-speed, rear-end impact for the four ISPs considered since the head acceleration plots deviated within the range of PIT head acceleration plots for different human subjects. This ensures that the second part of the study with neck injury using computer simulation results is a reliable testing procedure. It can be observed that MADYMO results have a greater error when compared to PIT when more than one OOP condition is employed as in TLHFP. All these observations would help in providing a tool to better understand the injury mechanisms and provide an accurate testing procedure for rear-end impact.