Brain injury environment critically influences the connectivity of transplanted neurons

Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative connectomics unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain, versus exuberant after trauma. In the latter, excessive synapse pruning follows the initial overshoot of connectivity resulting in only a few connections left. Proteomic profiling identifies candidate molecules involved in the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.

All-viral tracing of monosynaptic inputs to single birthdate-defined neurons in the intact brain

Neuronal firing patterns are the result of inputs converging onto single cells. Identifying these inputs, anatomically and functionally, is essential to understand how neurons integrate information. Single-cell electroporation of helper genes and subsequent local injection of recombinant rabies viruses enable precise mapping of inputs to individual cells in superficial layers of the intact cortex. However, access to neurons in deeper structures requires more invasive procedures, including removal of overlying tissue. We have developed a method that through a combination of virus injections allows us to target ≤4 hippocampal cells 48% of the time and a single cell 16% of the time in wildtype mice without the use of electroporation or tissue aspiration. We identify local and distant monosynaptic inputs that can be functionally characterised in vivo. By expanding the toolbox for monosynaptic circuit tracing, this method will help further our understanding of neuronal integration at the level of single cells.

Involvement of denervated midbrain-derived factors in the formation of ectopic cortico-mesencephalic projection after hemispherectomy

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain to compensate for the lost function, but the underlying molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at P6, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by astrocytes or microglia. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit beta 3 (Itgb3) or neurotrophic receptor tyrosine kinase 2 (Ntrk2, also known as TrkB) was knocked out. Overall, the present study suggests that midbrain-derived glial factors whose expression is upregulated after hemispherectomy are involved in lesion-induced remodeling of the cortico-mesencephalic projection.

Root Growth Phenology, Anatomy, and Morphology among root orders in Vaccinium macrocarpon Ait.

Understanding mechanisms controlling plant growth is essential to maintain and increase productivity in managed ecosystems. However, the lack of information on below ground growth compared to above ground growth limits our ability to adjust crop management practices under changing climate. This study examines seasonal fine-root growth and its spatial distribution through the soil profile across the growing season, and the anatomical and morphological traits of roots according to their branching order in Vaccinium macrocarpon Ait. Root production followed a unimodal curve, with one marked flush of root growth starting at bloom, with a peak at the end of fruit maturation. Root vertical distribution concentrated in the upper 5 cm of soil depth, accounting for over 50% of new roots produced during the study. Root anatomy and morphology was related to root function, as the first three root orders had intact cortex and epidermis and high mycorrhizal colonization indicative of absorptive function, while orders 5th and higher had secondary development and presence of a cambium cork layer indicative of translocation. Our study highlights the importance of examining timing of root growth and root traits by root order and its implications for the timing of fertilization and other practices in managed ecosystems.

Aneurysmal bone cyst in the pelvis of a cat: successful outcome of partial iliectomy with limb preservation

Case summary A 3-year-old spayed female domestic shorthair indoor cat presented with a 3-week history of pain from the pelvic region. Physical examination revealed pain elicited on palpating the pelvic area and right hip. Radiographs and CT showed an expansile, osteolytic process with intact cortex in the right wing of the ilium. CT revealed a monostotic and soft tissue-attenuating process with clear margins. Preoperative histopathological diagnosis of aneurysmal bone cyst was made from incisional biopsies. The cyst was removed en bloc with limb-sparing partial iliectomy. Histopathology confirmed the diagnosis of aneurysmal bone cyst. Recovery from surgery was uneventful. At re-examination 8 weeks and 8 months postoperatively, the cat was pain free and physical examinations were within normal limits. Relevance and novel information Feline aneurysmal bone cysts are rare and reported cases are few. To our knowledge, this is the first report describing the CT appearance of a pelvic aneurysmal bone cyst and partial iliectomy with limb preservation in a cat with successful short-term outcome.

Patterned perturbation of inhibition can reveal the dynamical structure of neural processing

Perturbation of neuronal activity is key to understanding the brain’s functional properties, however, intervention studies typically perturb neurons in a nonspecific manner. Recent optogenetics techniques have enabled patterned perturbations, in which specific patterns of activity can be invoked in identified target neurons to reveal more specific cortical function. Here, we argue that patterned perturbation of neurons is in fact necessary to reveal the specific dynamics of inhibitory stabilization, emerging in cortical networks with strong excitatory and inhibitory functional subnetworks, as recently reported in mouse visual cortex. We propose a specific perturbative signature of these networks and investigate how this can be measured under different experimental conditions. Functionally, rapid spontaneous transitions between selective ensembles of neurons emerge in such networks, consistent with experimental results. Our study outlines the dynamical and functional properties of feature-specific inhibitory-stabilized networks, and suggests experimental protocols that can be used to detect them in the intact cortex.

Local sleep-like cortical reactivity in the awake brain after focal injury

The functional consequences of brain injury are known to depend on neuronal alterations extending beyond the area of structural damage. Although a lateralized EEG slowing over the injured hemisphere was known since the early days of clinical neurophysiology, its electrophysiological mechanisms were not systematically investigated. In parallel, basic sleep research has thoroughly characterized the neuronal events underlying EEG slow waves in physiological conditions. These EEG events reflect brief interruptions of neuronal firing (OFF-periods) that can occur locally and have prominent consequences on network and behavioral functions. Notably, the EEG slow waves observed following focal brain injury have been never explicitly connected to local sleep-like neuronal events. In previous works, probing cortical circuits with transcranial magnetic stimulation coupled with EEG (TMS/EEG) proved as an effective way to reveal the tendency of cortical circuits to transiently plunge into silent OFF-periods. Here, using this approach, we show that the intact cortex surrounding focal brain injuries engages locally in pathological sleep-like dynamics. Specifically, we employed TMS/EEG in a cohort of thirty conscious awake patients with chronic focal and multifocal brain injuries of various etiologies. TMS systematically evoked prominent slow waves associated with sleep-like OFF-periods in the area surrounding focal cortico-subcortical lesions. These events were associated with a local disruption of signal complexity and were absent when stimulating the contralateral hemisphere. Perilesional sleep-like OFF-periods may represent a valid read-out of the electrophysiological state of discrete cortical circuits following brain injury as well as a potential target of interventions aimed at fostering functional recovery.One Sentence SummaryFocal cortical injuries are associated with local intrusion of sleep-like dynamics over the perilesional areas which disrupt local signal complexity and coexist with typical wakefulness cortical reactivity patterns within the same brain.

Musculoskeletal Interventions: The Basics

Comparable to other trends in medicine toward minimally invasive approaches, there has been a steady increase in demand for image-guided musculoskeletal (MSK) interventions. Interventional radiologists are involved in a variety of MSK interventions, including diagnostic, therapeutic, and palliative procedures. While many of the concepts that apply to other organs also apply to the MSK system, some are unique. This chapter will review MSK anatomy relevant to the safe and effective performance of biopsy, ablation, sclerotherapy, and embolization. It also will review imaging modalities used for MSK intervention and the special instruments that are used to access bony targets with an intact cortex. Finally, optimizing conditions for intervention, including patient position, anesthesia, use of buffers, and intraoperative nerve monitoring, will be discussed.

Faisal’s Technique to Closely Manage Volar Barton’s Fracture: A Pilot Study

This study was conducted to establish the efficacy of closed reduction and percutaneous pinning (CRPCP) in management of volar Barton’s fracture by Faisal Technique. Methods: A total of 10 cases of volar Barton’s fracture fulfilling our inclusion and exclusion criteria were included in our study from August 2015 to August 2016. These cases, presented at our department, were managed with closed reduction under image intensifier by dorsiflexing the wrist and reducing the fragment by ligamentotaxis and percutaneous pinning in anti-glide fashion from dorsal proximal (intact cortex) aspect of distal radius and engaging the volar fragment aiming the subchondral cortex and were supplemented with short arm cast application in volar flexion. The outcome was evaluated using Pattee and Thompson functional criteria at 6 month. Also the percentage of union and time to union were evaluated. Results: The mean age of total ten patients was 29.8± 3.20 years (25-35 years). We achieved union in 100% of the patient at mean time of 8.20 ± 0.92 weeks (7-10 weeks). There were 20% (n=2) cases with excellentand 80% (n=8) cases with good outcome according to Pattee and Thompson criteria. We had two cases (20%) with pin-tract infection that were managed with dressing and oral antibiotics according to culture and sensitivity. There were no loss of reduction Conclusion: Our pilot study demonstrates good result with CRPCP (Faisal’s Technique) in volar Barton’s fracture and warrants further randomized control trial study to establish its efficacy in such cases.