Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+(hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.

A somewhat perplexing finding in the systems neuroscience has been the observation that physical injury to neural systems may result in enhanced functional connectivity (i.e., hyperconnectivity) relative to the typical network response. The consequences of local or global enhancement of functional connectivity remain uncertain and this is particularly true for the overall metabolic cost of the network. We examine the hyperconnectivity hypothesis in a sample of 14 individuals with TBI with data collected at approximately 3, 6, and 12 months following moderate and severe TBI. As anticipated, individuals with TBI showed increased network strength and cost early after injury, but by one-year post injury hyperconnectivity was more circumscribed to frontal DMN and temporal-parietal attentional control regions. Cost in these subregions was a significant predictor of cognitive performance. Cost-efficiency analysis in the Power 264 data parcellation suggested that at 6 months post injury the network requires higher cost connections to achieve high efficiency as compared to the network 12 months post injury. These results demonstrate that networks self-organize to re-establish connectivity while balancing cost-efficiency trade-offs.

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Animals localise sound by making use of acoustical cues resulting from space and frequency dependent filtering of sound by the head and body. Sound arrives at each ear at different times, with different intensities, and with varying spectral content, all of which are affected by the animal's head and the relative sound source position. Location cues in mammals benefit from structures (pinnae) that modify these cues and provide information that helps resolve the cone of confusion and provide cues to sound source elevation. Animals without pinnae must rely on other mechanisms to solve localisation problems. Most non-mammals lack pinna-like structures, but some possess other anatomical features that could influence hearing. One such animal is the frill-necked lizard ( Chlamydosaurus kingii). The species' elaborate neck frill has been speculated to act as an aid to hearing, but no acoustical measurements have been reported. In this study, we characterise the frill's influence on the acoustical information available to the animal. Results suggest that the change in binaural cues is not sufficiently large to impact localisation behavior within the species' likely audiometric range; however, the frill does increase gain for sounds directly in front of the animal similar to a directional microphone.

Animal studies have revealed that moderate-level noise exposure can cause a permanent loss of ribbon synapses between inner hair cells and auditory-nerve fibers, but only temporary threshold shifts. Such noise-induced cochlear synaptopathy has been called ‘hidden hearing loss’ because while there is a significant degeneration of ribbon synapses, the resulting hearing dysfunction is effectively hidden from typical clinical assays. Here we used guinea pigs to study the mechanisms leading to hearing deficits resulting from a moderate noise. We measured distortion product otoacoustic emissions and auditory brainstem responses to assay peripheral hearing. We tested spatial hearing ability through the prepulse inhibition (PPI) of the acoustic startle reflex. PPI was used to measure hearing-in-noise ability, or spatial release from masking, as this task approximates the “cocktail party” effect. Finally, we performed immunohistochemistry to confirm synaptopathy. Results show that the noise exposure induces no permanent hearing threshold shift, but despite recovery of normal audibility, both behavioral and electrophysiological binaural hearing deficits persisted. Cochlear synaptopathy was objectively confirmed by visualizing the loss of ribbon synapses in the cochlea. The results demonstrate that cochlear synaptopathy causes deficits in brainstem circuits known to be critical for binaural and spatial hearing. [Work supported by Otolaryngology T32 DC012280.]