Journal of neurotrauma
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Journal of neurotrauma · Jun 2021
Nitric oxide/cGMP signaling via guanylyl cyclase isoform 1 mediates early changes in synaptic transmission and brain edema formation after TBI.
Traumatic brain injury (TBI) often induces structural damage, disruption of the blood-brain barrier (BBB), neurodegeneration, and dysfunctions of surviving neuronal networks. Nitric oxide (NO) signaling has been suggested to affect brain functions after TBI. The NO exhibits most of its biological effects by activation of the primary targets-guanylyl cyclases (NO-GCs), which exists in two isoforms (NO-GC1 and NO-GC2), and the subsequently produced cyclic guanosine monophosphate (cGMP). ⋯ Interestingly, NO-GC1 KO mice revealed relatively less BBB rupture and a weaker brain edema formation early after TBI. Further, lack of NO-GC1 also prevented the impaired synaptic transmission and network function that were observed in TBI-treated WT mice. These data suggest that NO-GC1 signaling mediates early brain damage and the strength of ipsilateral cortical network in the early phase after TBI.
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Journal of neurotrauma · Jun 2021
Case ReportsTractography-Pathology Correlations in Traumatic Brain Injury: A TRACK-TBI Study.
Diffusion tractography magnetic resonance imaging (MRI) can infer changes in network connectivity in patients with traumatic brain injury (TBI), but the pathological substrates of disconnected tracts have not been well defined because of a lack of high-resolution imaging with histopathological validation. We developed an ex vivo MRI protocol to analyze tract terminations at 750-μm isotropic resolution, followed by histopathological evaluation of white matter pathology, and applied these methods to a 60-year-old man who died 26 days after TBI. ⋯ Multiple linear regression revealed that tract disruption strongly correlated with the density of APP-positive axonal swellings and neurofilament loss. Ex vivo diffusion MRI can detect tract disruptions in the human brain that reflect axonal injury.
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Journal of neurotrauma · Jun 2021
Adipose tissue-derived mesenchymal stem cell concentrated conditioned medium alters the expression pattern of glutamate regulatory proteins and aquaporin-4 in the retina after mild traumatic brain injury.
Concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (ASC-CCM) show promise for retinal degenerative diseases. In this study, we hypothesized that ASC-CCM could rescue retinal damage and thereby improve visual function by acting through Müller glia in mild traumatic brain injury (mTBI). Adult C57Bl/6 mice were subjected to a 50-psi air pulse on the left side of the head, resulting in an mTBI. ⋯ Additionally, an increase in aquaporin-4 (AQP4) in Müller cells in blast mice received saline restored to normal levels in blast mice that received ASC-CCM. In vitro studies on rMC-1 Müller glia exposed to 100 ng/mL glutamate or RNA interference knockdown of GLAST expression mimicked the increased Müller cell glial fibrillary acidic protein (a marker of gliosis) seen with mTBI, and suggested that an increase in glutamate and/or a decrease in GLAST might contribute to the Müller cell activation in vivo. Taken together, our data suggest a novel neuroprotective role for ASC-CCM in the rescue of the visual deficits and pathologies of mTBI via restoration of Müller cell health.
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Journal of neurotrauma · Jun 2021
Interactive TutorialAssessment of compression driven shock tube designs in replicating free-field blast conditions for TBI studies.
Compression driven shock tubes are indispensable in studies of blast-induced traumatic brain injury (bTBI). The ability of shock tubes in faithfully recreating free-field blast conditions is of enormous interest and has a direct impact on injury outcomes. Toward this end, the evolution of blast wave inside and outside of the compression driven shock tube has been studied using validated, finite element based shock tube models. ⋯ Locations outside the shock tube are affected by jet-wind effects because of the sudden expansion, barring a narrow region at the exit. For the desired overpressure yield inferred in bTBI, obtaining positive phase durations of <1 msec inside the shock tube, which are sought for studies in rodents, is challenging. Overall, these results underscore that replicating free-field blast conditions using a shock tube involves tradeoffs that need to be weighed carefully and their effect on injury outcomes should be evaluated during laboratory bTBI investigations.