Persistent Infiltration and Impaired Response of Peripherally-Derived Monocytes after Traumatic Brain Injury in the Aged Brain.

Traumatic brain injury (TBI) is a leading cause for neurological disabilities world-wide. TBI occurs most frequently among the elderly population, and elderly TBI survivors suffer from reduced recovery and poorer quality of life. The effect of age on the pathophysiology of TBI is still poorly understood. We previously established that peripherally-derived monocytes (CCR2⁺) infiltrate the injured brain and contribute to chronic TBI-induced cognitive deficits in young animals. Furthermore, age was shown to amplify monocyte infiltration acutely after injury. In the current study, we investigated the impact of age on the subchronic response of peripherally-derived monocytes (CD45hi; CCR2⁺) and their role in the development of chronic cognitive deficits. In the aged brain, there was a significant increase in the number of peripherally-derived monocytes after injury compared to young, injured animals. The infiltration rate of peripherally-derived monocytes remained elevated subchronically and corresponded with enhanced expression of CCR2 chemotactic ligands. Interestingly, the myeloid cell populations observed in injured aged brains had impaired anti-inflammatory responses compared to those in young animals. Additionally, in the aged animals, there was an expansion of the blood CCR2⁺ monocyte population after injury that was not present in the young animals. Importantly, knocking out CCR2 to inhibit infiltration of peripherally-derived monocytes prevented chronic TBI-induced spatial memory deficits in the aged mice. Altogether, these results demonstrate the critical effects of age on the peripherally-derived monocyte response during the progression of TBI pathophysiology

Network resonance and the auditory steady state response.

The auditory steady state response (ASSR) arises when periodic sounds evoke stable responses in auditory networks that reflect the acoustic characteristics of the stimuli, such as the amplitude of the sound envelope. Larger for some stimulus rates than others, the ASSR in the human electroencephalogram (EEG) is notably maximal for sounds modulated in amplitude at 40 Hz. To investigate the local circuit underpinnings of the large ASSR to 40 Hz amplitude-modulated (AM) sounds, we acquired skull EEG and local field potential (LFP) recordings from primary auditory cortex (A1) in the rat during the presentation of 20, 30, 40, 50, and 80 Hz AM tones. 40 Hz AM tones elicited the largest ASSR from the EEG acquired above auditory cortex and the LFP acquired from each cortical layer in A1. The large ASSR in the EEG to 40 Hz AM tones was not due to larger instantaneous amplitude of the signals or to greater phase alignment of the LFP across the cortical layers. Instead, it resulted from decreased latency variability (or enhanced temporal consistency) of the 40 Hz response. Statistical models indicate the EEG signal was best predicted by LFPs in either the most superficial or deep cortical layers, suggesting deep layer coordinators of the ASSR. Overall, our results indicate that the recruitment of non-uniform but more temporally consistent responses across A1 layers underlie the larger ASSR to amplitude-modulated tones at 40 Hz

In vivo metabolic imaging of Traumatic Brain Injury.

Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway. We then used the colony-stimulating factor-1 receptor inhibitor PLX5622 to deplete brain resident microglia prior to and after CCI, in order to confirm that modulations of HP [1-13C] lactate-to-pyruvate ratios were linked to microglial activation. Despite CCI, the HP [1-13C] lactate-to-pyruvate ratio at the injury cortex of microglia-depleted animals at 7 days post-injury remained unchanged compared to contralateral hemisphere, and PDH activity was not affected. Altogether, our results demonstrate that HP [1-13C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI, providing a new tool to monitor the effect of therapies targeting microglia/macrophages activation after TBI

Temporary microglia-depletion after cosmic radiation modifies phagocytic activity and prevents cognitive deficits.

Microglia are the main immune component in the brain that can regulate neuronal health and synapse function. Exposure to cosmic radiation can cause long-term cognitive impairments in rodent models thereby presenting potential obstacles for astronauts engaged in deep space travel. The mechanism/s for how cosmic radiation induces cognitive deficits are currently unknown. We find that temporary microglia depletion, one week after cosmic radiation, prevents the development of long-term memory deficits. Gene array profiling reveals that acute microglia depletion alters the late neuroinflammatory response to cosmic radiation. The repopulated microglia present a modified functional phenotype with reduced expression of scavenger receptors, lysosome membrane protein and complement receptor, all shown to be involved in microglia-synapses interaction. The lower phagocytic activity observed in the repopulated microglia is paralleled by improved synaptic protein expression. Our data provide mechanistic evidence for the role of microglia in the development of cognitive deficits after cosmic radiation exposure

Diagnosing Acute Compartment Syndrome: A Surgical Emergency

Determine best practices for diagnosing acute compartment syndrome in the lower limb by comparing the sensitivity and specificity of commonly use techniques

Subsurface processes generated by bore-driven swash on coarse-grained beaches

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Sgt1, but not Rar1, is essential for the RB-mediated broad-spectrum resistance to potato late blight

<p>Abstract</p> <p>Background</p> <p>Late blight is the most serious potato disease world-wide. The most effective and environmentally sound way for controlling late blight is to incorporate natural resistance into potato cultivars. Several late blight resistance genes have been cloned recently. However, there is almost no information available about the resistance pathways mediated by any of those genes.</p> <p>Results</p> <p>We previously cloned a late blight resistance gene, <it>RB</it>, from a diploid wild potato species <it>Solanum bulbocastanum</it>. Transgenic potato lines containing a single <it>RB </it>gene showed a rate-limiting resistance against all known races of <it>Phytophthora infestans</it>, the late blight pathogen. To better understand the <it>RB</it>-mediated resistance we silenced the potato <it>Rar1 </it>and <it>Sgt1 </it>genes that have been implicated in mediating disease resistance responses against various plant pathogens and pests. The <it>Rar1 </it>and <it>Sgt1 </it>genes of a <it>RB</it>-containing potato clone were silenced using a RNA interference (RNAi)-based approach. All of the silenced potato plants displayed phenotypically normal growth. The late blight resistance of the <it>Rar1 </it>and <it>Sgt1 </it>silenced lines were evaluated by a traditional greenhouse inoculation method and quantified using a GFP-tagged <it>P. infestans </it>strain. The resistance of the <it>Rar1</it>-silenced plants was not affected. However, silencing of the <it>Sgt1 </it>gene abolished the <it>RB</it>-mediated resistance.</p> <p>Conclusion</p> <p>Our study shows that silencing of the <it>Sgt1 </it>gene in potato does not result in lethality. However, the <it>Sgt1 </it>gene is essential for the <it>RB</it>-mediated late blight resistance. In contrast, the <it>Rar1 </it>gene is not required for <it>RB</it>-mediated resistance. These results provide additional evidence for the universal role of the <it>Sgt1 </it>gene in various <it>R </it>gene-mediated plant defense responses.</p

Experimental study of bore-driven swash hydrodynamics on permeable rough slopes

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