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44
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Introduction
My current research interest is the evaluation of how acute brain injury can lead to severe and long-lasting consequences. I am using both animals models of TBI as well as clinically available biomarkers like the MRI to assess the axonal damage.
Current institution
Current position
- Head, Unit of Pathobiology and Neuroimaging
Additional affiliations
September 2010 - present
October 2012 - October 2016
Publications
Publications (44)
Background and Objectives
Severe Traumatic Brain Injury (TBI) is associated with secondary injury and poor outcomes, but the underlying mechanisms are poorly understood. Vascular mechanisms may be important. We aimed to characterise how blood vascular endothelial growth factor A (VEGF-A) levels are affected by TBI, and its associations with seconda...
Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%. While there are several potential explana...
Pathophysiology and outcomes after Traumatic Brain Injury (TBI) are complex and heterogenous. Current classifications are uninformative about pathophysiology. Proteomic approaches with fluid-based biomarkers are ideal for exploring complex disease mechanisms, as they enable sensitive assessment of an expansive range of processes potentially relevan...
Traumatic brain injury (TBI) is an alteration of brain function caused by a sudden transmission of an external force to the head. The biomechanical impact induces acute and chronic metabolic changes that highly contribute to injury evolution and outcome. TBI heterogeneity calls for approaches allowing the mapping of regional molecular and metabolic...
Pathophysiology and outcomes after Traumatic Brain Injury (TBI) are complex and highly heterogenous. Current classifications are uninformative about pathophysiology, which limits prognostication and treatment. Fluid-based biomarkers can identify pathways and proteins relevant to TBI pathophysiology. Proteomic approaches are well suited to exploring...
Aim We aimed to evaluate the quality of clinical evidence that substantiated approval of cancer medicines by European Medicines Agency (EMA) in the last decade. Methods We performed a systematic review and data synthesis of EMA documents in agreement with PRISMA guidelines. We included European Public Assessment Reports, Summaries of Product Charac...
Rodent models are important research tools for studying the pathophysiology of traumatic brain injury (TBI) and developing potential new therapeutic interventions for this devastating neurological disorder. However, the failure rate for the translation of drugs from animal testing to human treatments for TBI is 100%, perhaps due, in part, to distin...
Background
Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheime...
The latency between traumatic brain injury (TBI) and the onset of epilepsy (PTE) represents an opportunity for counteracting epileptogenesis. Antiepileptogenesis trials are hampered by the lack of sensitive biomarkers that allow to enrich patient's population at-risk for PTE. We aimed to assess whether specific ECoG signals predict PTE in a clinica...
A novel organotypic cortical slice culture model for traumatic brain injury: molecular changes induced by injury and mesenchymal stromal cell secretome treatment. Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a...
Introduction
A significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn...
Alzheimer’s disease (AD), the leading cause of dementia in older adults, is a double proteinopathy characterized by amyloid-β (Aβ) and tau pathology. Despite enormous efforts that have been spent in the last decades to find effective therapies, late pharmacological interventions along the course of the disease, inaccurate clinical methodologies in...
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result compa...
Mild traumatic brain injury (mTBI) mostly causes transient symptoms, but repeated (r)mTBI can lead to neurodegenerative processes. Diagnostic tools to evaluate the presence of ongoing occult neuropathology are lacking. In a mouse model of rmTBI we investigated MRI and plasma biomarkers of brain damage before chronic functional impairment arose. Ane...
Background
Outcomes after traumatic brain injury (TBI) are variable and frequently poor. Axonal injury is considered a significant determinant of outcome, which may be quantified using novel fluid biomark- ers and advanced MRI.
Methods
BIO-AX-TBI is a multi-centre cohort study of acute moderate-severe TBI. Patients underwent clinical and blood bio...
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce Sta...
Aneurysmal subarachnoid hemorrhage (SAH) is a substantial cause of mortality and morbidity worldwide. Moreover, survivors after the initial bleeding are often subject to secondary brain injuries and delayed cerebral ischemia, further increasing the risk of a poor outcome. In recent years, the renin–angiotensin system (RAS) has been proposed as a ta...
Traumatic brain injury is increasingly common in older individuals. Older age is one of the strongest predictors for poor prognosis after brain trauma, a phenomenon driven by the presence of extra-cranial comorbidities as well as pre-existent pathologies associated with cognitive impairment and brain volume loss (such as cerebrovascular disease or...
Background
TBI is an environmental risk factor for the development of dementia. Axonal injury is thought be a significant determinant of clinical outcomes post‐injury, which can now be assessed using novel techniques such as fluid biomarkers including plasma neurofilament light and advanced MRI assessment.
Method
BIO‐AX‐TBI (Developing and Validat...
Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TB...
We aimed to evaluate the quality of clinical evidence that substantiated approval of cancer medicines by the European Medicines Agency (EMA) in the last decade. We performed a systematic review and data synthesis of EMA documents in agreement with PRISMA guidelines. We included the European Public Assessment Reports, Summaries of Product Characteri...
Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies and 10–20% of the acquired forms. The latency between traumatic brain injury (TBI) and epilepsy onset in high-risk patients offers a therapeutic window for intervention to prevent or improve the disease course. However, progress towards effective treatments has been hampered by the lac...
Previous studies have shown that adolescent exposure to cocaine increases drug use in adulthood, albeit incubation of cocaine seeking was found to be attenuated in rats trained to self‐administer cocaine during adolescence. We here hypothesize that adolescent exposure to cocaine could alter the rewarding properties of the psychostimulant in adultho...
Introduction and aims
Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these lo...
Introduction and aims: Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these l...
Background: Whilst there has been progress in supportive treatment for traumatic brain injury (TBI), specific neuro- protective interventions are lacking. Models of ischaemic heart and brain injury show the therapeutic potential of argon gas, but it is still not known whether inhaled argon (iAr) is protective in TBI. We tested the effects of acute...
Traumatic brain injury (TBI) is a major cause of death and disability. Despite progress in neurosurgery and critical care, patients still lack a form of neuroprotective treatment that can counteract or attenuate injury progression. Inflammation after TBI is a key modulator of injury progression and neurodegeneration, but its spatiotemporal dissemin...
Nicotine‐associated cues can trigger reinstatement in humans as well as in animal models of drug addiction. To date, no behavioral intervention or pharmacological treatment has been effective in preventing relapse in the long term. A large body of evidence indicates that N‐acetylcysteine (N‐AC) blunts the activation of glutamatergic (GLUergic) neur...
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In the last 30 years several neuroprotective agents, attenuating the downstream molecular and cellular damaging events triggered by TBI, have been extensively studied. Even though many drugs have shown promising results in the pre-clinical stage, all have failed in l...
3,4-Dichloro-N-benzamide (AH-7921) is a cyclohexyl-methylbenzamide derivative with analgesic activity, whose abuse was associated with several fatal intoxications, included in Schedule I of UN Single Convention on Narcotic Drugs. We validated an HPLC-MS/MS method to investigate its brain disposition and metabolism after single and repeated injectio...
Purpose:
Asparaginase (ASNase) is used to treat various hematological malignancies for its capacity to deplete asparagine (ASN) in serum and cerebrospinal fluid (CSF). Since the biological mechanisms underlying CSF asparagine depletion in humans are not yet fully elucidated, this study compared, for the first time, the pharmacological properties o...
Para-methyl-4-methylaminorex (4,4′-DMAR) is a phenethylamine derivative with psychostimulant activity, whose abuse has been associated with several deaths and a wide range of adverse effects. We recently validated an HPLC-MS/MS method to measure the compound's concentrations in plasma, and applied it to describe the pharmacokinetic properties after...
Rationale
Although brain-derived neurotrophic factor (BDNF) is part of a homeostatic pathway involved in the development of alcohol dependence, it is not clear whether this is also true after recreational ethanol consumption.
Objectives
We examined BDNF expression and signaling in the cortico-striatal network immediately and 24 h after either a sin...
Chronic self-administration of nicotine induces maladaptive changes in the cortico-accumbal glutamate (Glu) network. Consequently, re-exposure to nicotine-associated cues raises extracellular Glu in the nucleus accumbens reinstating drug-seeking. Restoring basal concentrations of extracellular Glu, thereby increasing tonic activation of the presyna...
• The new psychoactive drugs (NPS) are a wide series of new substances that have been designed to mimick the psychotropic effect of traditional illicit drugs [Council Decision 2005/387/JHA of 20 May 2005]. • The principal problem of these substances is that they are not controlled by national drug laws and manufacturers of these compounds replace f...
• The new psychoactive drugs (NPS) are a wide series of new substances that have been designed to mimicking the psychotropic effect of traditional illicit drugs (Council Decision 2005/387/JHA). • The most obvious problem of these substances is that they are not controlled by national drug law and manufacturers of these compounds replace functional...
We previously demonstrated that nELAV/GAP-43 pathway is pivotal for learning and its hippocampal expression is up-regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence-induced stress may sustain nELAV/GAP-43 pathway during early abstinence following 2 weeks of cocaine self-administration. We...
Increases in alpha calcium/calmodulin-dependent protein kinase type II (αCaMKII) activity in the nucleus accumbens shell has been proposed as a core component in the motivation to self-administer cocaine and in priming-induced drug-seeking. Since cocaine withdrawal promotes drug-seeking, we hypothesized that abstinence from cocaine self-administrat...
Pharmacological stimulation of N-methyl-D-aspartate receptors (NMDAr) could enhance the outcome of cue-exposure therapy for smoking cessation. NMDAr stimulation can be achieved by increasing pharmacologically the synaptic levels of glycine, a necessary co-agonist. Here, we evaluate the effects of SSR504734, a selective inhibitor of glycine type I t...
Brain-derived neurotrophic factor (BDNF) dynamic changes were investigated in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) during use and the early phases of cocaine abstinence after 14 sessions (2 h self-administration/d; 0.25 mg/0.1 ml.6 s infusion) by employing a 'yoked control-operant paradigm'. The effect on BDNF was region-...
