Biomarkers identification in cerebrospinal fluid: new approaches for discriminating Central Nervous System disorders in veterinary neurology
Central nervous system (CNS) disorders represent a broad spectrum of diseases of different ethiologies. The therapeutic approach is extremely different for each of these conditions, and the indicated therapy for a specific CNS disease may be critically detrimental for a different one. Cerebrospinal fluid (CSF) surrounds and permeates the CNS. In patients with CNS disorders, the CSF is routinely analyzed for its cellular and chemical composition, and for specific antibodies and infectious agents research, representing a mainstay for the diagnosis of inflammatory CNS disorders. However, current techniques for the CSF analysis do not have high sensitivity and specificity in discriminate different CNS disorders, and for this reason developing other CSF biomarkers is fundamental to further improve the diagnostic value of this analysis.
When the nervous tissue is injured in the course of a CNS pathology, immune system cells, especially different sub-types of CD4 T-cells, produce and release inflammatory mediators such as cytokines, chemokines and growth factors in the CSF, with particular patterns based on the sub-type of cells activated by each etiopathogenetic mechanism.
These different CSF patterns have been evaluated in human medicine, suggesting their utility as biomarkers in early diagnosis, prognosis, and monitoring process. Currently, in veterinary literature cytokines and chemokines CSF profile has been evaluated only in association with certain CNS disorders with promising results.
Another extremely promising biomarker studied in human medicine is the Neurofilament light chain (NfL), one of three subunits of the Neurofilament (NFs) that compose the axonal cytoskeleton. NFs levels increase within the CSF and the blood after axonal damage, so they may be used as biomarker able to quantify neuronal damage in various CNS diseases even before the occurrence of severe clinical signs, to predict probable disorder progression and to monitor the effects of therapies.
In veterinary medicine, the role of NfL as a CSF biomarker has been evaluated only once to date, and the study identified a potential utility of NfL for the diagnosis, prognosis, and monitoring of meningoencephalitis of unknown etiology (MUE) in dogs
Based on these premises, the aim of the present PhD project is to evaluate specific CSF patterns of cytokines and chemokines and CSF and blood NfL concentration in different small and large animals’ neurological disorders. The main and primary objective is to improve the possibilities of a prompt diagnosis, especially the capability to discriminate among different CNS diseases, with mild invasive procedures such as blood and CSF collection and analysis. An early identification of the ongoing pathology is essential to promote an appropriate and rational usage of drugs, and to reduce the mortality associated with these conditions.
Specifically, the research project will consist of the sequent objectives:
- Evaluation and quantification of a selected panel of cytokines and chemokines on CSF samples collected from large and small animals referred to the Neurology Service of the Veterinary Teaching Hospital (VTH) of Turin with a CNS disease.
- Evaluation and quantification of NfL on blood and CSF samples collected from the population mentioned above. Assessment of the correlation between blood and CSF NfL concentration.
- Assessment of the feasibility of individual molecules in distinguishing between different CNS disorders, development of specific CSF biomarkers profiles for each category of CNS disease and proposal of an algorithm for CNS diseases diagnosis using these data.
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Attended courses and congress
34th ESVN-ECVN Symposium, 22th-24th September 2022, Palma de Mallorca, Spain
Grant Writing Course - How to write a Competitive
Practical course by SCIVAC "Neurodiagnostica RM", 30th June-2nd July 2022, Cremona, Italy
Live webinar by ESAOTE "MRI of CNS Vascular diseases by Dr. Cristian Falzone", 27th April 2022, online meeting
SINVET Meeting with Dennis O'Brien, 9th April 2022, online meeting
Theoretical-practical course "Filmmaking for Scientists", 13th-17th December 2022, Turin, Italy
SINVET Meeting “Diagnostica per immagini in neurologia veterinaria: quanto avanzata?”, 27th November 2021, online meeting
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