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MicroRNAs signature and TBI: diagnosis, prognosis and functional studies
Valentina Di Pietro, Antonio Belli
We have discovered that several microRNAs are expressed in blood, saliva and urine of TBI patients within minutes of injury. These are differentially expressed in different TBI severities and outcomes, reflecting differential pathophysiological responses to injury. MicroRNAs are silencing and post-transcriptional regulators of gene expression, and capture the multidimentionality of host-response at tissue and systemic leveI. They modulate downstream processes in brain and systemic targets, and dynamically continue to do so as the pathology evolves. The discovery of a new regulatory signalling into TBI pathology represents a step-change for molecular TBI research.
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Neuroinflammatory proteins in TBI
Valentina Di Pietro/Lisa J Hill/Antonio Belli
Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. Neuroinflammation is responsible for both beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. For all these reasons, these inflammatory molecules could satisfy the main characteristics required for a biomarker in the diagnosis and prognosis of TBI. In particular, the early identification of these biomarkers could permit clinicians to recognise and treat those patients at risk of secondary injury while they are still capable of responding to therapy before irreversible damages occur.
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Metabolism and mitochondrial dynamics of severe and mild TBI in an in vivo animal model
Valentina Di Pietro/Antonio Belli/external collaborators: Prof. Giuseppe Lazzarino University of Catania and Prof. Barbara Tavazzi Catholic University of Rome
Using different approaches (HPLC to analyse biochemical alterations of energy metabolism and oxidative/nitrosative stresses, microarray to analyse gene expression profile) the metabolic, enzymatic and gene changes following graded diffuse traumatic brain injury (TBI) are studied in a weight drop model of TBI in rats.
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Neurobioreactors: a new in vitro stretch injury device
Valentina Di Pietro /Antonio Belli
This project developed a reliable and reproducible platform for testing drugs and other neuroprotective strategies using an in vitro model of organotypic hippocampal slice cultures.
The cultures are stretched on a silicone membrane to mimic in vivo tissue deformation experienced during TBI
The novelty of this study is to understand the molecular changes occurring in TBI in a “clean” environment without the systemic confounders of the in vivo model. A prototype of the model has already been built thanks to the ongoing collaboration with Dr Alastair Campbell Ritchie (UoN). The prototype uses pneumatic pressure as the actuation method, giving greater flexibility in stimulation regimens than current methods using direct physical displacement.
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Development of point-of-care diagnostic devices
Valentina Di Pietro/Antonio Belli/Biovici diagnostics
Over 1.4 million people attend UK Emergency Department every year with a traumatic brain injury (TBI). Many more suffer concussion during contact sports but are not treated in hospital. Timely diagnosis of TBI is key, where paramedics draw blood samples at the roadside. We have identified highly sensitive, ultra-early biomarkers of TBI consisting of microRNAs. However, a sensitive biomarker would be no use for roadside or pitch-side diagnosis if samples still needed analysing in a hospital lab. We have therefore partnered with Biovici diagnostic, a company who is developing a rapid portable and low-cost detection method.
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Micro-optofluidic engineered device technology (MEDtech) for timely assessment of TBI
Collaboration with Dr. P. Goldberg Oppenheimer, School of Chemical Engineering, UoB
In this project a highly-innovative, reliable, diagnostic technology for rapid detection of biomarkers at a picomolar range capable of discriminating between different analytes from complex bio-fluids has been developed. The portable, minimally-invasive MEDTech is based on cost-effective, controllable electrohydrodynamic (EHD) sub-microstructures engineered for multiplexed-surface enhanced Raman scattering (SERS) detection. It combines sensitive, reproducible and molecule-specific EHD-SERS lab-on-a-chip with miniaturised optofluidic platforms for on-the-spot biomarkers detection, either individually or as a panel, to enable real-time diagnostics and care-delivery.
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Functional Near-Infrared Spectroscopy (fNIRS) on TBI patients
Mario Forcione/Antonio Belli
Number of studies proved a strict correlation between the Functional Near-Infrared Spectroscopy (fNIRS) and the Functional Magnetic Resonance Imaging (fMRI) to measure brain activity. Using the fMRI, a different activation pattern in TBI patients compared to control group has been shown in cognitive exercises.
The aims of this study are: to detect if the fNIRS is able to show a different brain activation pattern between TBI patients and healthy controls; to monitor the recovery of TBI patients with different levels of cardiovascular fitness; to compare the fNIRS with TBI biomarkers.