Showing papers by "David Communi published in 2023"
TL;DR: In this paper , the authors collected samples of ventricular cerebrospinal fluid (vCSF) for 5 days in 50 consecutive patients at risk of intracranial hypertension after traumatic and nontraumatic ABI.
Abstract: BACKGROUND
Danger-associated molecular patterns (DAMPs) may be implicated in the pathophysiological pathways associated with an unfavorable outcome after acute brain injury (ABI).
METHODS
We collected samples of ventricular cerebrospinal fluid (vCSF) for 5 days in 50 consecutive patients at risk of intracranial hypertension after traumatic and nontraumatic ABI. Differences in vCSF protein expression over time were evaluated using linear models and selected for functional network analysis using the PANTHER and STRING databases. The primary exposure of interest was the type of brain injury (traumatic vs. nontraumatic), and the primary outcome was the vCSF expression of DAMPs. Secondary exposures of interest included the occurrence of intracranial pressure ≥20 or ≥ 30 mm Hg during the 5 days post-ABI, intensive care unit (ICU) mortality, and neurological outcome (assessed using the Glasgow Outcome Score) at 3 months post-ICU discharge. Secondary outcomes included associations of these exposures with the vCSF expression of DAMPs.
RESULTS
A network of 6 DAMPs (DAMP_trauma; protein-protein interaction [PPI] P=0.04) was differentially expressed in patients with ABI of traumatic origin compared with those with nontraumatic ABI. ABI patients with intracranial pressure ≥30 mm Hg differentially expressed a set of 38 DAMPS (DAMP_ICP30; PPI P< 0.001). Proteins in DAMP_ICP30 are involved in cellular proteolysis, complement pathway activation, and post-translational modifications. There were no relationships between DAMP expression and ICU mortality or unfavorable versus favorable outcomes.
CONCLUSIONS
Specific patterns of vCSF DAMP expression differentiated between traumatic and nontraumatic types of ABI and were associated with increased episodes of severe intracranial hypertension.
TL;DR: In this article , the authors performed an in vitro characterization of human induced pluripotent stem cell-derived sensory neuronal cultures highly enriched for primary proprioceptive neurons, and the results indicated the existence of abnormalities affecting proprioceptors in Friedreich ataxia, particularly their ability to extend towards their targets and transmit proper synaptic signals.
Abstract: Abstract Friedreich ataxia is an autosomal recessive multisystem disorder with prominent neurological manifestations and cardiac involvement. The disease is caused by large GAA expansions in the first intron of the FXN gene, encoding the mitochondrial protein frataxin, resulting in downregulation of gene expression and reduced synthesis of frataxin. The selective loss of proprioceptive neurons is a hallmark of Friedreich ataxia, but the cause of the specific vulnerability of these cells is still unknown. We herein perform an in vitro characterization of human induced pluripotent stem cell-derived sensory neuronal cultures highly enriched for primary proprioceptive neurons. We employ neurons differentiated from healthy donors, Friedreich ataxia patients and Friedreich ataxia sibling isogenic control lines. The analysis of the transcriptomic and proteomic profile suggests an impairment of cytoskeleton organization at the growth cone, neurite extension and, at later stages of maturation, synaptic plasticity. Alterations in the spiking profile of tonic neurons are also observed at the electrophysiological analysis of mature neurons. Despite the reversal of the repressive epigenetic state at the FXN locus and the restoration of FXN expression, isogenic control neurons retain many features of Friedreich ataxia neurons. Our study suggests the existence of abnormalities affecting proprioceptors in Friedreich ataxia, particularly their ability to extend towards their targets and transmit proper synaptic signals. It also highlights the need for further investigations to better understand the mechanistic link between FXN silencing and proprioceptive degeneration in Friedreich ataxia.