How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World.

The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.

Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment.

Chemotherapy results in a frequent yet poorly understood syndrome of long-term neurological deficits. Neural precursor cell dysfunction and white matter dysfunction are thought to contribute to this debilitating syndrome. Here, we demonstrate persistent depletion of oligodendrocyte lineage cells in humans who received chemotherapy. Developing a mouse model of methotrexate chemotherapy-induced neurological dysfunction, we find a similar depletion of white matter OPCs, increased but incomplete OPC differentiation, and a persistent deficit in myelination. OPCs from chemotherapy-naive mice similarly exhibit increased differentiation when transplanted into the microenvironment of previously methotrexate-exposed brains, indicating an underlying microenvironmental perturbation. Methotrexate results in persistent activation of microglia and subsequent astrocyte activation that is dependent on inflammatory microglia. Microglial depletion normalizes oligodendroglial lineage dynamics, myelin microstructure, and cognitive behavior after methotrexate chemotherapy. These findings indicate that methotrexate chemotherapy exposure is associated with persistent tri-glial dysregulation and identify inflammatory microglia as a therapeutic target to abrogate chemotherapy-related cognitive impairment. VIDEO ABSTRACT.

Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion.

Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). By using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma xenograft model, we demonstrate that active neurons similarly promote HGG proliferation and growth in vivo. Conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures, indicating secretion of activity-regulated mitogen(s). The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen, and soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feedforward expression of NLGN3 in glioma cells. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted NLGN3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth.

NF1 mutation drives neuronal activity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.

Microglia in brain development and regeneration.

It has recently emerged that microglia, the tissue-resident macrophages of the central nervous system, play significant non-innate immune roles to support the development, maintenance, homeostasis and repair of the brain. Apart from being highly specialized brain phagocytes, microglia modulate the development and functions of neurons and glial cells through both direct and indirect interactions. Thus, recognizing the elements that influence the homeostasis and heterogeneity of microglia in normal brain development is crucial to understanding the mechanisms that lead to early disease pathogenesis of neurodevelopmental disorders. In this Review, we discuss recent studies that have elucidated the physiological development of microglia and summarize our knowledge of their non-innate immune functions in brain development and tissue repair.

Spatial and Temporal Relationships Between Atrophy and Hypometabolism in Behavioral-Variant Frontotemporal Dementia.

PURPOSE: Individuals with behavioral-variant frontotemporal dementia (bvFTD) show changes in brain structure as assessed by MRI and brain function assessed by 18FDG-PET hypometabolism. However, current understanding of the spatial and temporal interplay between these measures remains limited. METHODS: Here, we examined longitudinal atrophy and hypometabolism relationships in 15 bvFTD subjects with 2 to 4 follow-up MRI and PET scans (56 visits total). Subject-specific slopes of atrophy and hypometabolism over time were extracted across brain regions and correlated with baseline measures both locally, via Pearson correlations, and nonlocally, via sparse canonical correlation analyses (SCCA). RESULTS: Notably, we identified a robust link between initial hypometabolism and subsequent cortical atrophy rate changes in bvFTD subjects. Network-level exploration unveiled alignment between baseline hypometabolism and ensuing atrophy rates in the dorsal attention, language, and default mode networks. SCCA identified 2 significant and highly localized components depicting the connection between baseline hypometabolism and atrophy slope over time. The first centered around bilateral orbitofrontal, frontopolar, and medial prefrontal lobes, whereas the second concentrated in the left temporal lobe and precuneus. CONCLUSIONS: This study highlights 18FDG-PET as a dependable predictor of forthcoming atrophy in spatially adjacent brain regions for individuals with bvFTD.

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology.

INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aß) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aß, as assessed by 18F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aß were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aß. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aß-vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aß pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

Evaluation of mediastinoscopy for cranial mediastinal and tracheobronchial lymphadenectomy in canine cadavers.

OBJECTIVE: To report technical feasibility and describe procedural details of a novel single incision minimally invasive approach to the mediastinum in cadaver dogs. STUDY DESIGN: Cadaveric study. ANIMALS: Large breed (25-40 kg) cadaver dogs (n = 10). METHODS: Three of 10 cadavers were used for preliminary technique development without data recording. Cadaver specimens underwent pre- and postoperative thoracic computed tomographic scans. Seven dogs were placed in dorsal recumbency and mediastinoscopy was performed via a SILS port placed cranial to the thoracic inlet with CO2 insufflation of the mediastinum at 2-4 mmHg. Retrieval of all CT and visually identified mediastinal lymph nodes (LN) was attempted; endoscopic compartmental and individual LN dissection times and subjective operative challenges were recorded. Procedural success scores for visualization and dissection as well as NASA-task force index scores were recorded per lymph node, per cadaver. RESULTS: Median time required for initial approach including SILS placement was 5 min (range 5-10 min). Individual LN retrieval times ranged from 2 to 32 min. Mediastinoscopic retrieval of LNs was most commonly successful for the left tracheobronchial LN (7/7), followed by the right tracheobronchial LN (4/7), the left and right sternal LNs (3/7 each), and the cranial mediastinal LNs (1/7). Post-procedure pleural gas was identified on CT in 4/7 cadavers. CONCLUSIONS: Mediastinoscopy as reported was feasible in large breed canine cadavers and retrieval or cup biopsy of a variety of lymph nodes is possible from the described approach. Application in living animals and its associated challenges should be further investigated. CLINICAL SIGNIFICANCE: Mediastinoscopy may provide a novel minimally invasive approach to the evaluation and oncologic staging of the cranial mediastinum in dogs.

Neuroimaging feature extraction using a neural network classifier for imaging genetics.

BACKGROUND: Dealing with the high dimension of both neuroimaging data and genetic data is a difficult problem in the association of genetic data to neuroimaging. In this article, we tackle the latter problem with an eye toward developing solutions that are relevant for disease prediction. Supported by a vast literature on the predictive power of neural networks, our proposed solution uses neural networks to extract from neuroimaging data features that are relevant for predicting Alzheimer's Disease (AD) for subsequent relation to genetics. The neuroimaging-genetic pipeline we propose is comprised of image processing, neuroimaging feature extraction and genetic association steps. We present a neural network classifier for extracting neuroimaging features that are related with the disease. The proposed method is data-driven and requires no expert advice or a priori selection of regions of interest. We further propose a multivariate regression with priors specified in the Bayesian framework that allows for group sparsity at multiple levels including SNPs and genes. RESULTS: We find the features extracted with our proposed method are better predictors of AD than features used previously in the literature suggesting that single nucleotide polymorphisms (SNPs) related to the features extracted by our proposed method are also more relevant for AD. Our neuroimaging-genetic pipeline lead to the identification of some overlapping and more importantly some different SNPs when compared to those identified with previously used features. CONCLUSIONS: The pipeline we propose combines machine learning and statistical methods to benefit from the strong predictive performance of blackbox models to extract relevant features while preserving the interpretation provided by Bayesian models for genetic association. Finally, we argue in favour of using automatic feature extraction, such as the method we propose, in addition to ROI or voxelwise analysis to find potentially novel disease-relevant SNPs that may not be detected when using ROIs or voxels alone.

EEG variability: Task-driven or subject-driven signal of interest?

Neurons in the brain are seldom perfectly quiet. They continually receive input and generate output, resulting in highly variable patterns of ongoing activity. Yet the functional significance of this variability is not well understood. If brain signal variability is functionally relevant and serves as an important indicator of cognitive function, then it should be highly sensitive to the precise manner in which a cognitive system is engaged and/or relate strongly to differences in behavioral performance. To test this, we examined EEG activity in younger adults as they performed a cognitive skill learning task and during rest. Several measures of EEG variability and signal strength were calculated in overlapping time windows that spanned the trial interval. We performed a systematic examination of the factors that most strongly influenced the variability and strength of EEG activity. First, we examined the relative sensitivity of each measure to across-subject variation (within blocks) and across-block variation (within subjects). We found that the across-subject variation in EEG variability and signal strength was much stronger than the across-block variation. Second, we examined the sensitivity of each measure to different sources of across-block variation during skill acquisition. We found that key task-driven changes in EEG activity were best reflected in changes in the strength, rather than the variability, of EEG activity. Lastly, we examined across-subject variation in each measure and its relationship with behavior. We found that individual differences in response time measures were best reflected in individual differences in the variability, rather than the strength, of EEG activity. Importantly, we found that individual differences in EEG variability related strongly to stable indicators of subject identity rather than dynamic indicators of subject performance. We therefore suggest that EEG variability may provide a more sensitive subject-driven measure of individual differences than task-driven signal of interest.

Perioperative characteristics, histologic diagnosis, complications, and outcomes of dogs undergoing percutaneous drainage, sclerotherapy or surgical management of intrarenal cystic lesions: 18 dogs (2004-2021).

BACKGROUND: Canine intrarenal cystic lesions (ICLs) are infrequently reported in the veterinary literature. Several treatment options have been described including cyst fenestration (partial nephrectomy/deroofing) +/- omentalization, sclerotherapy using alcohol as a sclerosing agent, percutaneous cyst drainage (PCD), and ureteronephrectomy. Information regarding presenting clinical signs, physical examination findings, histologic diagnosis and outcomes of dogs with ICLs treated by different methods is limited. Medical records of 11 institutions were retrospectively reviewed to identify dogs that underwent PCD, sclerotherapy, surgical deroofing +/- omentalization, or ureteronephrectomy for management of ICLs from 2004 to 2021. Six weeks postoperative/post-procedural follow-up was required. Cases suspected to represent malignancy on preoperative imaging were excluded. The study objective was to provide information regarding perioperative characteristics, complications, and outcomes of dogs undergoing treatment of ICLs. RESULTS: Eighteen dogs were included, with 24 ICLs treated. Ten had bilateral. There were 15 males and 3 females, with crossbreeds predominating. PCD, sclerotherapy, deroofing and ureteronephrectomy were performed in 5 (5 ICLs treated), 7 (11 ICLs), 6 (6), and 7 (7) dogs, respectively, with 5 dogs undergoing > 1 treatment. Seven dogs experienced 8 complications, with requirement for additional intervention commonest. PCD, sclerotherapy and deroofing resulted in ICL resolution in 0/5, 3/11 and 3/6 treated ICLs, respectively. Histopathology identified renal cysts (RCs) in 7/13 dogs with histopathology available and neoplasia in 6/13 (4 malignant, 2 benign). Of 5 dogs diagnosed histopathologically with neoplasia, cytology of cystic fluid failed to identify neoplastic cells. Among 7 dogs with histologically confirmed RCs, 4 had concurrent ICLs in ipsilateral/contralateral kidney, compared with 2/6 dogs with histologically confirmed neoplasia. CONCLUSIONS: Benign and neoplastic ICLs were approximately equally common and cystic fluid cytology failed to differentiate the 2. Among renal-sparing treatments, deroofing most commonly resulted in ICL resolution. Presence of concurrent ICLs in ipsilateral/contralateral kidney does not appear reliable in differentiating benign from malignant ICLs.

Evaluation of transanal minimally invasive surgery for submucosal rectal resection in cadaveric canine specimens.

OBJECTIVE: To evaluate the feasibility of transanal minimally invasive surgery (TAMIS) for submucosal rectal resection in large breed dogs. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Canine cadavers (n = 6) weighing between 37.5 and 60 kg. METHODS: Dogs were positioned in sternal recumbency. After rectal cleansing, a transanal access platform was placed in the rectum, and a pneumorectum was established. An area of ventral rectal wall approximately 2 × 2 cm was resected in a submucosal plane by using laparoscopic instruments and submitted for histopathological evaluation. The rectal wall defect was closed with a single-layer continuous suture pattern with barbed suture. Postoperatively, the rectum was removed en bloc and evaluated for suture or surgical penetration of the serosal surface. RESULTS: Submucosal rectal resection was successfully completed by using TAMIS in all dogs. The median length of resected specimens after fixation was 24.5 mm (range 9.8-26.5). In two of six dogs, suture was macroscopically visible on the serosal surface, but no dogs had evidence of iatrogenic full-thickness surgical penetration of the rectum. The median distance from the aborad extent of the suture closure line to the anocutaneous junction was 35 mm (range, 35-105). CONCLUSION: Submucosal resection of the canine rectal wall was feasible in large breed dogs by using TAMIS. No evidence of full-thickness penetration of the rectal wall was seen in these cadaveric specimens. CLINICAL SIGNIFICANCE: Transanal minimally invasive surgery may provide an alternative minimally invasive approach for resection for benign adenomatous rectal polyps in large breed dogs that might otherwise require a rectal pull-through.

Emerging mechanistic underpinnings and therapeutic targets for chemotherapy-related cognitive impairment.

PURPOSE OF REVIEW: Modern innovations in cancer therapy have dramatically increased the number of cancer survivors. An unfortunately frequent side-effect of cancer treatment is enduring neurological impairment. Persistent deficits in attention, concentration, memory, and speed of information processing afflict a substantial fraction of cancer survivors following completion of these life-saving therapies. Here, we highlight chemotherapy-related cognitive impairment (CRCI) and discuss the current understanding of mechanisms underlying CRCI. RECENT FINDINGS: New studies emphasize the deleterious impact of chemotherapeutic agents on glial-glial and neuron-glial interactions that shape the form, function and plasticity of the central nervous system. An emerging theme in cancer therapy-related cognitive impairment is therapy-induced microglial activation and consequent dysfunction of both neural precursor cells and mature neural cell types. Recent work has highlighted the complexity of dysregulated intercellular interactions involving oligodendrocyte lineage cells, microglia, astrocytes, and neurons following exposure to traditional cancer therapies such as methotrexate. This new understanding of the mechanistic underpinnings of CRCI has elucidated potential therapeutic interventions, including colony-stimulating factor 1 receptor inhibition, TrkB agonism, and aerobic exercise. SUMMARY: Traditional cancer therapies induce lasting alterations to multiple neural cell types. Therapy-induced microglial activation is a critical component of the cause of CRCI, contributing to dysregulation of numerous processes of neural plasticity. Therapeutic targeting of microglial activation or the consequent dysregulation of neural plasticity mechanisms are emerging.

Utility of bronchoscopy combined with surgery in the treatment and outcomes of dogs with intrathoracic disease secondary to plant awn migration.

OBJECTIVE: To evaluate the diagnostic and therapeutic utility of bronchoscopy in dogs undergoing computed tomography (CT) and surgery for intrathoracic disease (pyothorax and pneumothorax) secondary to migrating plant awns (MPA) and to report outcomes in dogs that did and did not undergo bronchoscopy in addition to CT and surgery. STUDY DESIGN: Retrospective case series. ANIMALS: Thirty-seven client-owned dogs. METHODS: Medical records from 2008 to 2017 were reviewed for dogs with documented MPA in the thoracic cavity treated with CT and surgery with or without bronchoscopy. Information regarding diagnostics, treatments, complications, and outcomes relating to hospitalization was evaluated. RESULTS: At least one abnormal lung lobe was identified by CT in all dogs. Bronchial abnormalities were identified with bronchoscopy in 21 of 22 dogs (95.4%) with available reports. Agreement between CT and bronchoscopy findings ranged from 50% to 81.8%, depending on lung lobe. Thirty-six dogs had one or more lung lobes surgically removed. Thirty-seven MPA were retrieved via bronchoscopy in 10 of 27 (37%) dogs, and 39 MPA were retrieved at surgery in 26 of 37 (70.3%) dogs. Actinomyces spp. were cultured from surgical samples in 7 of 33 (21.2%) dogs. Thirty-five of 37 (94.6%) dogs survived to discharge. CONCLUSION: Migrating plant awns were successfully retrieved via bronchoscopy. Agreement between CT findings and bronchoscopy was inconsistent, so there may be roles for both modalities. Short- and long-term survival was excellent in this cohort. CLINICAL SIGNIFICANCE: Bronchoscopy may allow for diagnostic and therapeutic advantages compared with CT in dogs with endobronchial MPA. Actinomyces spp appear to be variably present in surgically acquired bacterial cultures in dogs with MPA.

Notes from the Field: Furanyl-Fentanyl Overdose Events Caused by Smoking Contaminated Crack Cocaine - British Columbia, Canada, July 15-18, 2016.

On July 15 2016, Surrey Memorial Hospital's emergency department notified the medical health officer on call of a sharp increase in opioid overdose events in Surrey, Fraser Health Authority, in British Columbia, Canada. During July 15-18, the number of persons with suspected opioid overdose evaluated in Surrey Memorial Hospital's emergency department increased approximately 170%, from an average of four suspected cases per day during the period January-June 2016 to 43 (nearly 11 per day) during the 4-day period (Figure). Most patients (22 [51%]) became unconscious after smoking what they believed to be crack cocaine. The majority of overdose events occurred within a small geographic area in Surrey that has a high population of homeless persons and persons who use illicit drugs, including opioids and crack cocaine. Most cases occurred in males (36 cases [84%]); the average age of the patients was 42 years (range = 18-63 years). Forty (93%) patients were brought to the emergency department by ambulance. A total of 37 (86%) patients received injectable naloxone before arriving in the emergency department, including 12 who received it only from community members, 16 who received it only from paramedics, five who received it from both community members and paramedics, one who received it from the fire department and paramedics, and one who received it from the fire department, community, and paramedics; for two patients, the source of naloxone was not known. Reports from first responders, the community, and emergency department staff members indicated that patients required high doses of injectable naloxone, in some cases up to 3.0 mg (usual dose = 0.4 mg). Thirty-five (81%) patients were treated and discharged within a few hours, two patients left without being seen by a health care provider, and six patients were admitted to the hospital; among these, three were transferred to the intensive care unit, one of whom died.

Trail Making Test Elucidates Neural Substrates of Specific Poststroke Executive Dysfunctions.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment is typified by prominent deficits in processing speed and executive function. However, the underlying neuroanatomical substrates of executive deficits are not well understood, and further elucidation is needed. There may be utility in fractionating executive functions to delineate neural substrates. METHODS: One test amenable to fine delineation is the Trail Making Test (TMT), which emphasizes processing speed (TMT-A) and set shifting (TMT-B-A difference, proportion, quotient scores, and TMT-B set-shifting errors). The TMT was administered to 2 overt ischemic stroke cohorts from a multinational study: (1) a chronic stroke cohort (N=61) and (2) an acute-subacute stroke cohort (N=45). Volumetric quantification of ischemic stroke and white matter hyperintensities was done on magnetic resonance imaging, along with ratings of involvement of cholinergic projections, using the previously published cholinergic hyperintensities projections scale. Damage to the superior longitudinal fasciculus, which colocalizes with some cholinergic projections, was also documented. RESULTS: Multiple linear regression analyses were completed. Although larger infarcts (ß=0.37, P<0.0001) were associated with slower processing speed, cholinergic hyperintensities projections scale severity (ß=0.39, P<0.0001) was associated with all metrics of set shifting. Left superior longitudinal fasciculus damage, however, was only associated with the difference score (ß=0.17, P=0.03). These findings were replicated in both cohorts. Patients with ≥2 TMT-B set-shifting errors also had greater cholinergic hyperintensities projections scale severity. CONCLUSIONS: In this multinational stroke cohort study, damage to lateral cholinergic pathways and the superior longitudinal fasciculus emerged as significant neuroanatomical correlates for executive deficits in set shifting.

Augmenting Veterinary Minimally Invasive Surgery: Evidence-based Review of Foundational and Novel Devices and Technology.

Veterinary minimally invasive surgery continues to grow as a specialty. With increasing experience in this field, comes improved accessibility as well as progressive complexity of procedures performed. Advancement in technology has been both a response to the growth and a necessary driver of continued refinement of this field. Innovative research leading to advancements in surgical equipment has led to the development of novel image acquisition platforms, cannulas, smoke evacuation systems, antifog devices, instrumentation, and ligating/hemostatic devices. These innovations will be reviewed and potential clinical applications are discussed.

Precise timing of audiovisual stimulation conquers chemobrain.

In a recent study, Kim et al. utilized gamma entrainment using sensory stimuli (GENUS) to rescue cognitive impairment and glial dysregulation associated with cisplatin and methotrexate chemotherapy, specifically when applied both throughout and after chemotherapy administration. GENUS provides a time-dependent, non-invasive method for treating chemobrain, with broader implications for resolving neurodegenerative neuroinflammation.

Canine Prostate Cancer: Current Treatments and the Role of Interventional Oncology.

Prostate carcinoma is one of the most common cancers worldwide in men, with over 3 million men currently living with prostate carcinoma. In men, routine screening and successful treatment schemes, including radiation, prostatectomy, or hormone therapy, have allowed for high survivability. Dogs are recognized as one of the only mammals to spontaneously develop prostate neoplasia and are an important translational model. Within veterinary medicine, treatment options have historically been limited in efficacy or paired with high morbidity. Recently, less invasive treatment modalities have been investigated in dogs and people and demonstrated promise. Below, current treatment options available in dogs and people are reviewed, as well as a discussion of current and future trends within interventional treatment for canine PC.

Oligodendrocytes: Myelination, Plasticity, and Axonal Support.

The myelination of axons has evolved to enable fast and efficient transduction of electrical signals in the vertebrate nervous system. Acting as an electric insulator, the myelin sheath is a multilamellar membrane structure around axonal segments generated by the spiral wrapping and subsequent compaction of oligodendroglial plasma membranes. These oligodendrocytes are metabolically active and remain functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of metabolites and macromolecules to and from the internodal periaxonal space under the myelin sheath. Increasing evidence indicates that oligodendrocyte numbers, specifically in the forebrain, and myelin as a dynamic cellular compartment can both respond to physiological demands, collectively referred to as adaptive myelination. This review summarizes our current understanding of how myelin is generated, how its function is dynamically regulated, and how oligodendrocytes support the long-term integrity of myelinated axons.