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Frontiers in Immunology 2023Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid...
BACKGROUND AND OBJECTIVES
Encephalitis is a devastating neurologic disorder with high morbidity and mortality. Autoimmune causes are roughly as common as infectious ones. N-methyl-D-aspartic acid receptor (NMDAR) encephalitis (NMDARE), characterized by serum and/or spinal fluid NMDAR antibodies, is the most common form of autoimmune encephalitis (AE). A translational rodent NMDARE model would allow for pathophysiologic studies of AE, leading to advances in the diagnosis and treatment of this debilitating neuropsychiatric disorder. The main objective of this work was to identify optimal active immunization conditions for NMDARE in mice.
METHODS
Female C57BL/6J mice aged 8 weeks old were injected subcutaneously with an emulsion of complete Freund's adjuvant, killed and dessicated , and a 30 amino acid peptide flanking the NMDAR GluN1 subunit N368/G369 residue targeted by NMDARE patients' antibodies. Three different induction methods were examined using subcutaneous injection of the peptide emulsion mixture into mice in 1) the ventral surface, 2) the dorsal surface, or 3) the dorsal surface with reimmunization at 4 and 8 weeks (boosted). Mice were bled biweekly and sacrificed at 2, 4, 6, 8, and 14 weeks. Serum and CSF NMDAR antibody titer, mouse behavior, hippocampal cell surface and postsynaptic NMDAR cluster density, and brain immune cell entry and cytokine content were examined.
RESULTS
All immunized mice produced serum and CSF NMDAR antibodies, which peaked at 6 weeks in the serum and at 6 (ventral and dorsal boosted) or 8 weeks (dorsal unboosted) post-immunization in the CSF, and demonstrated decreased hippocampal NMDAR cluster density by 6 weeks post-immunization. In contrast to dorsally-immunized mice, ventrally-induced mice displayed a translationally-relevant phenotype including memory deficits and depressive behavior, changes in cerebral cytokines, and entry of T-cells into the brain at the 4-week timepoint. A similar phenotype of memory dysfunction and anxiety was seen in dorsally-immunized mice only when they were serially boosted, which also resulted in higher antibody titers.
DISCUSSION
Our study revealed induction method-dependent differences in active immunization mouse models of NMDARE disease. A novel ventrally-induced NMDARE model demonstrated characteristics of AE earlier compared to dorsally-induced animals and is likely suitable for most short-term studies. However, boosting and improving the durability of the immune response might be preferred in prolonged longitudinal studies.
Topics: Mice; Female; Animals; Emulsions; Mice, Inbred C57BL; Encephalitis; Antibodies; Receptors, N-Methyl-D-Aspartate; Vaccination; Disease Models, Animal; Autoimmune Diseases of the Nervous System
PubMed: 37520559
DOI: 10.3389/fimmu.2023.1177672 -
Chirurgia (Bucharest, Romania : 1990) Aug 2023While ventral hernia repair is a frequent surgical intervention, the possibility of complications remains present. The use of drains to mitigate complications is a... (Observational Study)
Observational Study
While ventral hernia repair is a frequent surgical intervention, the possibility of complications remains present. The use of drains to mitigate complications is a topic of debate, with conflicting evidence. This study aimed to evaluate the association between drain usage and postoperative complications in ventral hernia repair. A single-center prospective study included patients undergoing ventral hernia repair from 2018 to 2022. Patient data and surgical techniques were recorded. Statistical analysis was performed to assess risk factors for drain insertion and complications. Of the 216 patients included, 19.44% had diabetes, and 20% had cancer. Postoperative complications (Clavien Dindo grade IIIB) occurred in 9.3% of cases, resulting in a 3.7% mortality. Decision factors for drain insertion included older age, larger hernia size, bowel resection with anastomosis, emergency setting and the need for adhesiolysis. No differences were found between the two groups regarding seroma and hematoma formation and mesh infection. Patients with drains had a longer hospital stay and higher costs. Conclusion: The decision to use drains in ventral hernia repair was influenced by surgical complexity factors rather than patient characteristics. While drain usage did not correlate with postoperative morbidities, it was associated with longer hospitalization and higher costs. Individualized decision-making is crucial to balance complications and resource utilization in ventral hernia repair.
Topics: Humans; Prospective Studies; Treatment Outcome; Drainage; Postoperative Complications; Hernia, Ventral
PubMed: 37698005
DOI: 10.21614/chirurgia.2023.v.118.i.4.p.426 -
Frontiers in Surgery 2022The successful repair of any complex ventral hernia requires a thorough understanding of the underlying anatomical defect and its functional context. We describe an...
PURPOSE
The successful repair of any complex ventral hernia requires a thorough understanding of the underlying anatomical defect and its functional context. We describe an improved "functional" approach to CT imaging of the abdominal wall that can facilitate this understanding and assist surgical planning.
METHODS
This invited article reports the observational experience gained from the functional abdominal wall CT examinations of 88 patients who underwent complex ventral hernia repair using pre-operative Botulinum toxin A (BTA) infiltration of the lateral oblique abdominal muscles as well as a further eight patients with diastasis rectus abdominis who were examined to exclude ventral hernia.
RESULTS
The use of a functional CT protocol which supplements resting images with additional "crunching" images (acquired with the abdominal wall muscles all strongly contracted) can significantly improve the demonstration of ventral hernia defects. Crunching acquisitions can also help differentiate true hernias from dysfunctional bulges, identify muscle denervation or atrophic changes, reveal otherwise occult hernias that may be missed on resting or Valsalva images alone, and assist the pre-operative assessment of BTA effect.
CONCLUSION
A more functional approach to pre-operative CT imaging of the abdominal wall can significantly improve the understanding of complex ventral hernia defects and help formulate effective surgical plans that achieve low recurrence rates and good functional outcomes.
PubMed: 35284471
DOI: 10.3389/fsurg.2022.799277 -
Chirurgie (Heidelberg, Germany) Jan 2024In recent years many new surgical techniques for minimally invasive treatment of ventral hernias have been developed and introduced. This review article presents these... (Review)
Review
BACKGROUND
In recent years many new surgical techniques for minimally invasive treatment of ventral hernias have been developed and introduced. This review article presents these new minimally invasive surgical techniques, such as extended totally extraperitoneal (eTEP) repair, mini or less open sublay (MILOS), endoscopic-assisted linea alba reconstruction (ELAR), the ventral transabdominal preperitoneal patch (TAPP) technique, intraperitoneal onlay mesh (IPOM) plus and laparoscopic intracorporeal rectus aponeuroplasty (LIRA) and discusses recently published results.
RESULTS
Modern minimally invasive techniques for the treatment of ventral hernias have the potential to reduce surgical site infections, lower postoperative pain and lead to a shorter duration of hospital stay compared to the classical open hernia repair; however, especially techniques with a retromuscular mesh position are technically challenging due to the preparation in a limited space and difficult to perform endoscopic sutures and necessitate detailed knowledge of the anatomy of the abdominal wall. The treatment of larger hernias in particular should therefore only be carried out under the prerequisite of extensive experience and case numbers.
CONCLUSION
The new endoscopic and endoscopically assisted techniques for treatment of ventral hernias enable the experienced laparoscopic surgeon to primarily and secondarily treat ventral hernias with minimally invasive techniques.
Topics: Humans; Incisional Hernia; Surgical Mesh; Hernia, Ventral; Laparoscopy; Minimally Invasive Surgical Procedures
PubMed: 38071258
DOI: 10.1007/s00104-023-02000-x -
Surgical Neurology International 2021The epidural ligaments (ELs) (of Hofmann) were described as fibrous bands interconnecting the ventrolateral spinal dura and the posterior longitudinal ligament below L1.... (Review)
Review
BACKGROUND
The epidural ligaments (ELs) (of Hofmann) were described as fibrous bands interconnecting the ventrolateral spinal dura and the posterior longitudinal ligament below L1. They are hardly ever discussed in the literature or considered in hypothesis-driven basic science experiments or spine biomechanical models.
METHODS
Intraoperative photographs were obtained to illustrate a group of posterolateral spinal ELs. In addition, electronic database searches (PubMed, Ovid Embase, and SCOPUS) were utilized to summarize the anatomy, and relevant clinical and surgical factors impacting these ELs.
RESULTS
ELs attach circumferentially at most spinal levels. They anchor the nerve root sleeves ventrally, and therefore, may play a role in the some idiopathic neurologic deficits (e.g., postoperative radiculopathies, C5 palsies) in patients without radiological compression. The posterolateral ELs originate on the dura dorsal to the nerve root sleeves and insert on the ipsilateral lamina, interlaminar ligament, and facet capsule. They appear to be continuous with the peridural membrane, a fibrovascular sheath that surrounds the thecal sac and serves as a scaffold for the internal vertebral venous plexus of Batson and epidural fat.
CONCLUSION
The spinal ELs should be divided sharply during surgery to prevent durotomies, especially in patients with advanced spondylosis and facet arthropathy. Disconnecting these ligaments releases the thecal sac laterally and ventrally, allowing for medial mobilization when performing discectomies or for working in the ventral epidural space.
PubMed: 33598349
DOI: 10.25259/SNI_894_2020 -
Cerebral Cortex Communications 2023Despite their anatomical and functional distinctions, there is growing evidence that the dorsal and ventral visual pathways interact to support object recognition....
Despite their anatomical and functional distinctions, there is growing evidence that the dorsal and ventral visual pathways interact to support object recognition. However, the exact nature of these interactions remains poorly understood. Is the presence of identity-relevant object information in the dorsal pathway simply a byproduct of ventral input? Or, might the dorsal pathway be a source of input to the ventral pathway for object recognition? In the current study, we used high-density EEG-a technique with high temporal precision and spatial resolution sufficient to distinguish parietal and temporal lobes-to characterise the dynamics of dorsal and ventral pathways during object viewing. Using multivariate analyses, we found that category decoding in the dorsal pathway preceded that in the ventral pathway. Importantly, the dorsal pathway predicted the multivariate responses of the ventral pathway in a time-dependent manner, rather than the other way around. Together, these findings suggest that the dorsal pathway is a critical source of input to the ventral pathway for object recognition.
PubMed: 36726794
DOI: 10.1093/texcom/tgad003 -
Scientific Reports Jan 2022We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven...
We investigated the characteristics of midbrain injuries in patients with spontaneous subarachnoid hemorrhage (SAH) by using diffusion tensor imaging (DTI). Twenty-seven patients with SAH and 25 healthy control subjects were recruited for this study. Fractional anisotropy (FA) and mean diffusivity (MD) data were obtained for four regions of the midbrain (the anterior ventral midbrain, posterior ventral midbrain, tegmentum area, and tectum) in 27 hemispheres that did not show any pathology other than SAH. The mean FA and MD values of the four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) of the patient group were significantly lower and higher than those of the control group, respectively (p < 0.05). The mean FA values of the patient group were significantly different among the anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum regions (ANOVA; F = 3.22, p < 0.05). Post hoc testing showed that the mean FA value of the anterior ventral midbrain was significantly lower than those of the posterior ventral midbrain, tegmentum, and tectum (p < 0.05); in contrast, there were no differences in mean FA values of the posterior ventral midbrain, tegmentum, and tectum (p > 0.05). However, differences were not observed among four regions of the midbrain (anterior ventral midbrain, posterior ventral midbrain, tegmentum, and tectum) in the mean MD values. We detected evidence of neural injury in all four regions of the midbrain of patients with SAH, and the anterior ventral midbrain was the most severely injured among four regions of the midbrain. Our results suggest that a pathophysiological mechanism of these neural injuries might be related to the occurrence of a subarachnoid hematoma.
Topics: Adult; Aged; Brain Injuries; Diffusion Tensor Imaging; Female; Humans; Male; Mesencephalon; Middle Aged; Predictive Value of Tests; Retrospective Studies; Risk Factors; Subarachnoid Hemorrhage, Traumatic
PubMed: 34996928
DOI: 10.1038/s41598-021-03747-1 -
Cell Reports Jan 2022Goal-directed behavior requires identifying objects in the environment that can satisfy internal needs and executing actions to obtain those objects. The current study...
Goal-directed behavior requires identifying objects in the environment that can satisfy internal needs and executing actions to obtain those objects. The current study examines ventral and dorsal corticostriatal circuits that support complementary aspects of goal-directed behavior. We analyze activity from the amygdala, ventral striatum, orbitofrontal cortex, and lateral prefrontal cortex (LPFC) while monkeys perform a three-armed bandit task. Information about chosen stimuli and their value is primarily encoded in the amygdala, ventral striatum, and orbitofrontal cortex, while the spatial information is primarily encoded in the LPFC. Before the options are presented, information about the to-be-chosen stimulus is represented in the amygdala, ventral striatum, and orbitofrontal cortex; at the time of choice, the information is passed to the LPFC to direct a saccade. Thus, learned value information specifying behavioral goals is maintained throughout the ventral corticostriatal circuit, and it is routed through the dorsal circuit at the time actions are selected.
Topics: Amygdala; Animals; Choice Behavior; Conditioning, Operant; Fixation, Ocular; Goals; Macaca mulatta; Male; Parietal Lobe; Prefrontal Cortex; Reward; Saccades; Ventral Striatum
PubMed: 34986350
DOI: 10.1016/j.celrep.2021.110198 -
The Journal of Physiology Apr 2022Motivation boosts motor performance. Activity of the ventral midbrain (VM), consisting of the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) and...
Motivation boosts motor performance. Activity of the ventral midbrain (VM), consisting of the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) and the retrorubral field (RRF), plays an important role in processing motivation. However, little is known about the neural substrate bridging the VM and the spinal motor output. We hypothesized that the VM might exert a modulatory influence over the descending motor pathways. By retrograde transneuronal labelling with rabies virus, we demonstrated the existence of multisynaptic projections from the VM to the cervical enlargement in monkeys. The distribution pattern of spinal projection neurons in the VM exhibited a caudorostral gradient, in that the RRF and the caudal part of the SNc contained more retrogradely labelled neurons than the VTA and the rostral part of the SNc. Electrical stimulation of the VM induced muscle responses in the contralateral forelimb with a delay of a few milliseconds following the responses of the ipsilateral primary motor cortex (M1). The magnitude and number of evoked muscle responses were associated with the stimulus intensity and number of pulses. The muscle responses were diminished during M1 inactivation. Thus, the present study has identified a multisynaptic VM-spinal pathway that is mediated, at least in part, by the M1 and might play a pivotal role in modulatory control of the spinal motor output. KEY POINTS: Motivation to obtain reward is thought to boost motor performance, and activity in the ventral midbrain is important to the motivational process. Little is known about a neural substrate bridging the ventral midbrain and the spinal motor output. Retrograde trans-synaptic experiments revealed that the ventral midbrain projects multisynaptically to the spinal cord in macaque monkeys. Ventral midbrain activation by electrical stimulation generated cortical activity in the motor cortex and forelimb muscle activity. A multisynaptic ventral midbrain-spinal pathway most probably plays a pivotal role in modulatory control of the spinal motor output.
Topics: Animals; Haplorhini; Mesencephalon; Motor Cortex; Motor Neurons; Ventral Tegmental Area
PubMed: 35122444
DOI: 10.1113/JP282429