Conferences in the time of COVID: notes on organizing and delivering the first Brain Conference.

To further fulfil their missions of promoting teaching, education and research in neurology and related clinical-academic disciplines, the Guarantors of Brain and the Brain journal family invited delegates to the first Brain Conference in Spring of this year. This event aimed to deliver excellent teaching and scientific presentations across a broad spectrum of neuroscience fields, with the key aim of making the content as accessible as possible. We hoped to capitalize on the benefits of an online format, whilst trying to capture a little of the joy of the in-person meeting. This article reports on the approach and practical choices made to achieve these goals, and we hope this will provide some guidance and advice to others organizing their own online conference.

Does time heal all wounds? Experimental diffuse traumatic brain injury results in persisting histopathology in the thalamus.

BACKGROUND: Thalamic dysfunction has been implicated in overall chronic neurological dysfunction after traumatic brain injury (TBI), however little is known about the underlying histopathology. In experimental diffuse TBI (dTBI), we hypothesize that persisting histopathological changes in the ventral posteromedial (VPM) nucleus of the thalamus is indicative of progressive circuit reorganization. Since circuit reorganization in the VPM impacts the whisker sensory system, the histopathology could explain the development of hypersensitivity to whisker stimulation by 28days post-injury; similar to light and sound hypersensitivity in human TBI survivors. METHODS: Adult, male Sprague-Dawley rats underwent craniotomy and midline fluid percussion injury (FPI) (moderate severity; 1.8-2.0atm) or sham surgery. At 1d, 7d, and 28days post-FPI (d FPI) separate experiments confirmed the cytoarchitecture (Giemsa stain) and evaluated neuropathology (silver stain), activated astrocytes (GFAP), neuron morphology (Golgi stain) and microglial morphology (Iba-1) in the VPM. RESULTS: Cytoarchitecture was unchanged throughout the time course, similar to previously published data; however, neuropathology and astrocyte activation were significantly increased at 7d and 28d and activated microglia were present at all time points. Neuron morphology was dynamic over the time course with decreased dendritic complexity (fewer branch points; decreased length of processes) at 7d FPI and return to sham values by 28d FPI. CONCLUSIONS: These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.

Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury.

In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.