Giuseppe Biagini

Università degli Studi di Modena e Reggio Emilia | UNIMO · Department of Biomedical, Metabolical and Neurosciences

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on speech are still debated, particularly in the long-term follow-up. The objective of this study was to evaluate the long-term effects of bilateral STN-DBS on speech in a cohort of advanced...

Cannabis is a multifaceted plant with numerous therapeutic properties on one hand, and controversial psychotropic activities on the other hand, which are modulated by CB1 endocannabinoid receptors. Δ9-Tetrahydrocannabinol (Δ9-THC) has been identified as the main component responsible for the psychotropic effects, while its constitutional isomer can...

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the...

Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the 4th cause of end-stage renal disease in Western Countries, nevertheless still represents an illness with a significant unmet medical need. In recent years, deregulation in glucose metabolism in ADPKD has been identified. Data suggest that cystic cells shift their energy...

Background Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative‐based data, various studies have been published on GBA‐PD cohorts which suggested possible differences in dopamin...

Objective To assess the long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on gait in a cohort of advanced Parkinson’s Disease (PD) patients. Methods This observational study included consecutive PD patients treated with bilateral STN-DBS. Different stimulation and drug treatment conditions were assessed: on-stimul...

We obtained evidence that mouse BV2 microglia synthesize neurosteroids dynamically to modify neurosteroid levels in response to oxidative damage caused by rotenone. Here, we evaluated whether neurosteroids could be produced and altered in response to rotenone by the human microglial clone 3 (HMC3) cell line. To this aim, HMC3 cultures were exposed...

Objective: To evaluate correlations between speech and gait parameters in the long-term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's Disease (PD) patients. Methods: This observational study included consecutive PD patients treated with bilateral STN-DBS. Ax...

Cannabis is a double-faced plant with uncountable therapeutic properties, on one side, and controversial psychotropic activities, on the other side, modulated by CB1 endocannabinoid receptors. Δ ⁹ -Tetrahydrocannabinol (Δ ⁹ -THC) has been identified as the main component responsible for the psychotropic effects, while its isomer cannabidiol (CBD) h...

Objective: Epileptogenesis after status epilepticus (SE) has a faster onset in rats treated to reduce brain levels of the anticonvulsant neurosteroid allopregnanolone with the 5α-reductase inhibitor finasteride; however, it still has to be evaluated whether treatments aimed at increasing allopregnanolone levels could result in the opposite effect o...

The evaluation of the chiral composition of phytocannabinoids in the cannabis plant is particularly important as the pharmacological effects of the (+) and (-) enantiomers of these compounds are completely different. Chromatographic attempts to assess the presence of the minor (+) enantiomers of the main phytocannabinoids, cannabidiolic acid (CBDA)...

1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxaz...

Epilepsy is a life-threatening neurological disease that affects approximately 70 million people worldwide. Although the vast majority of patients may be successfully managed with currently used antiseizure medication (ASM), the search for alternative therapies is still necessary due to pharmacoresistance in about 30% of patients with epilepsy. Her...

The peroxisome proliferator-activated receptor gamma (PPARγ), which belongs to the family of nuclear receptors, has been mainly studied as an important factor in metabolic disorders. However, in recent years the potential role of PPARγ in different neurological diseases has been increasingly investigated. Especially, in the search of therapeutic ta...

Multiple sclerosis (MS) is the most common inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. Chronic‐relapsing experimental autoimmune encephalomyelitis (crEAE) in Biozzi ABH mice is an experimental model of MS. This crEAE model is characterized by an acute phase with severe neurological disabi...

Epilepsy is reported in 29–52% of patients with glioblastoma (GBM) and has an important role in the natural history of this tumor and patients’ life quality. Although GBM is less epileptogenic than lower-grade gliomas, seizures are usually more difficult to control with common antiseizure medications; drug resistance is found in 20% of cases. Recen...

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (>5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twen...

Cannabidiolic acid (CBDA) and trans-Δ⁹-tetrahydrocannabinolic acid (trans-Δ⁹-THCA) are known to be the major phytocannabinoids in Cannabis sativa L., along with their decarboxylated derivatives cannabidiol (CBD) and trans-Δ⁹-tetrahydrocannabinol (trans-Δ⁹-THC). The cis isomer of Δ⁹-THC has been recently identified, characterized and quantified in s...

We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator activated receptor gamma (PPAR) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seve...

Children with epilepsy and identified as responders to antiseizure medications (ASMs) were found to present markedly higher ghrelin plasma levels when compared to drug-resistant patients. However, it was undetermined if this phenotype could be influenced by the ASMs. Here, we prospectively investigated total ghrelin and des-acyl ghrelin (DAG) plasm...

L-Kynurenine (KYN) and kynurenic acid (KYNA) are products of the metabolism of L-tryptophan (TRP) in the central nervous system of animals, but they are not commonly found in plants. In particular, KYNA is known for its interesting pharmacological properties (anti-oxidative, anti-inflammatory, hypolipidemic, and neuroprotective), which suggest a po...

Status epilepticus (SE) is a common neurological emergency with considerable associated health-care costs, morbidity, and mortality. In about one-third of cases, SE is refractory toward first-line intravenous benzodiazepines. Allopregnanolone, a neurosteroid that positively modulates synaptic and extrasynaptic γ-aminobutyric acid type A receptors,...

Compounds present in Cannabis sativa L. preparations have recently attracted much attention in the treatment of drug-resistant epilepsy. Here, we screened two olive oil extracts from a non-psychoactive C. sativa variety, fully characterized by high-performance liquid chromatography and gas chromatography. Particularly, hemp oils with different conc...

The recent discovery of the novel heptyl phytocannabinoids cannabidiphorol (CBDP) and Δ⁹-tetrahydrocannabiphorol (Δ⁹-THCP) raised a series of questions relating to the presence and abundance of these new unorthodox compounds in cannabis inflorescence or derived products. As fresh inflorescence contains mainly their acid precursors, which are not co...

Fundamental work on the mechanisms leading to focal epileptic discharges in mesial temporal lobe epilepsy (MTLE) often rests on the use of rodent models in which an initial status epilepticus (SE) is induced by kainic acid or pilocarpine. In 2008 we reviewed how, following systemic injection of pilocarpine, the main subsequent events are the initia...

A sensitive and straightforward HPLC-UV method was developed for the simultaneous quantification of the two main impurities in “pure” commercial cannabigerol (CBG) samples. The identification of such impurities, namely cannabigerovarin (CBGV) and cannabigerobutol (CBGB), the propyl and butyl homologs of CBG, respectively, was accomplished employing...

E-health technologies improve healthcare quality and disease management. The aim of this study was to develop a ketogenic diet management app as well as a website about this dietary treatment and to evaluate the benefits of giving caregivers access to various web materials designed for paediatric patients with refractory epilepsy. Forty families pa...

Editorial on the Research Topic Endocrine Modulators of Neurological Processes: Potential Treatment Targets of Pediatric Neurological Diseases

Abrupt withdrawal from antiepileptic drugs is followed by increased occurrence of epileptic seizures, a phenomenon known as the "rebound effect". By stopping treatment with le-vetiracetam (LEV 300 mg/kg/day, n = 15; vs saline, n = 15), we investigated the rebound effect in adult male Sprague-Dawley rats. LEV was continuously administered using osmo...

Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids-allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)-are known to modulate GABA A receptor-mediated transmission, thus playing a r...

Neurosteroids can modulate γ-aminobutyric acid type A receptor-mediated inhibitory currents. Recently, we discovered that the neurosteroids progesterone, 5α-dihydroprogesterone, allopregnanolone, and pregnanolone are reduced in the cerebrospinal fluid of patients with status epilepticus (SE). However, it is undetermined whether neurosteroids influe...

Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells. BV-2 cells were exposed to increasing concentrations...

Epilepsy contributes to approximately 1% of the global disease burden. By affecting especially young children as well as older persons of all social and racial variety, epilepsy is a present disorder worldwide. Currently, only 65% of epileptic patients can be successfully treated with antiepileptic drugs. For this reason, alternative medicine recei...

Introduction Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a condition that causes progressive renal function decline. Preclinical data suggest the presence of a profound metabolic derangement in ADPKD. Cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis, show inhibition of fatty acid oxidation...

The N-methyl-(2S,4R)-trans-4-hydroxy-L-proline-enriched fraction (NMP) from Sideroxylon obtusifolium was evaluated as a neuroprotective agent in the intracerebroventricular (icv) pilocarpine (Pilo) model. To this aim, male mice were subdivided into sham (SO, vehicle), Pilo (300 µg/1 µL icv, followed by the vehicle per os, po) and NMP-treated groups...

Background: Neurosteroids modulate epileptic activity by interacting with the γ-aminobutyric acid type A receptor, but their brain levels are still undetermined. Objectives: We aimed to establish levels of neurosteroids in the neocortex and hippocampus by liquid chromatography–mass spectrometry in epileptic rats. Methods: Kainic acid-treated rats w...

Background/aims: Status epilepticus (SE) might be followed by temporal lobe epilepsy (TLE), a common neurologic disorder characterized by spontaneous recurrent seizures (SRSs). However, the relationship between SE and TLE is still incompletely characterized. For this reason, in a model of TLE we evaluated the lesion extent and the onset of SRSs to...

Caregiver informative materials are an important complement to verbal interaction in medical encounters enhancing caregivers' health literacy and this is particularly true when dealing with treatments that are still little known, as is the ketogenic diet (KD) for pediatric refractory epilepsy in Italy. Their value is dependent upon whether they con...

The amygdala is a cerebral region whose function is compromised in temporal lobe epilepsy (TLE). Patients with TLE present cognitive and emotional dysfunctions, of which impairments in recognizing facial expressions have been clearly attributed to amygdala damage. However, damage to the amygdala has been scarcely addressed, with the majority of stu...

The ketogenic diet (KD) is a high-fat, low carbohydrate nutritional treatment adopted in several countries for refractory epilepsy. However, the use of KD is limited by adverse events including growth retardation. In a previous investigation, we demonstrated that ghrelin is reduced in children maintained on KD for 3 months. As ghrelin regulates gro...

Background Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the fourth cause of end stage renal disease (ESRD) and urgently requires the development of effective therapeutic treatments. The presence of a shift in energy metabolism from oxidative phosphorylation to aerobic glycolysis in ADPKD prompted us to explore the possibility to limit gl...

Background: Metabolic complications represent a common and serious problem associated with HIV infection and combined Antiretroviral Therapy (cART). Alterations in body fat distribution are associated with significantly increased risks of (i) metabolic derangements, (ii) cardiovascular pathologies, and (iii) insulin resistance. A case control study...

TLQP-21 is a neuropeptide which has been implicated in regulation of nociception and other relevant physiologic functions. Although recent studies identified C3a and gC1q receptors as targets for TLQP-21, its intracellular molecular mechanisms of action remain largely unidentified. Our aim was (i) to explore the intracellular signaling pathway(s) a...

Modulation of basal fluorescence in the presence of SOCE antagonists in RAW264.7 cells. Cells were loaded with FLUO-4 NW and treated with different inhibitors before the stimulation with HBSS. The lines show intracellular Ca2+ mobilization in RAW264.7 cells stimulated with HBSS alone and in presence of 10 μM SKF-96365 (20 min), 10 μM YM-58483 (20 m...

Effects of different inhibitors on basal fluorescence in RAW264.7 cells. Cells were loaded with FLUO-4 NW and treated with different inhibitors before the stimulation with HBSS. The lines show intracellular Ca2+ mobilization in RAW264.7 cells stimulated with HBSS alone and in presence of 2 μM CsA (15 min), 2 μM TG (20 min), 10 μM U73122 (10 min), o...

Effects of repeated stimulations on intracellular Ca2+ levels in RAW264.7 cells. Cells were loaded with FLUO-4 NW and fluorescence emissions were measured at 485/535 nm every 0.5 s for the 20 s preceding and the 60 s following the injection of the stimuli. 10 μM ATP was applied after 30 min from HBSS. HBSS and ATP were injected at the time indicate...

Repeated JMV5656 and ATP stimulations on intracellular Ca2+ levels in the presence of SOCE antagonists in RAW264.7 cells. Cells were loaded with FLUO-4 NW and treated with different inhibitors (10 μM SKF-96365 20 min, 10 μM YM-58483 20 min, 1 mM EGTA 30 min) before the stimulation with 1 μM JMV5656. 10 μM ATP was applied after 30 min from JMV5656....

Repeated JMV5656 and ATP stimulations on intracellular Ca2+ levels in RAW264.7 cells. Cells were loaded with FLUO-4 NW and treated with different inhibitors (2 μM TG 20 min, 10 μM U73122 10 min, 75 μM 2-APB 15 min) before the stimulation with 1 μM JMV5656. 10 μM ATP was applied after 30 min from JMV5656. JMV5656 and ATP were injected at the time in...

Recently, we showed that matrix metalloproteinase-12 (MMP-12) is highly expressed in microglia and myeloid infiltrates, which are presumably involved in blood-brain barrier (BBB) leakage and subsequent neuronal cell death that follows status epilepticus (SE). Here, we assessed the effects of a hydroxypyrone-based inhibitor selective for MMP-12 in t...

Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ‐aminobutyric acid type A (GABAA) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neuroster...

Objective To reconsider ghrelin and des-acyl ghrelin plasma levels in children with epilepsy in order to establish a possible relation with response to antiepileptic drugs (AEDs). Methods We designed an observational study in which 114 patients with epilepsy were classified as responders (77) or nonresponders (37) and compared to 59 controls. In t...

Background & aims: The gastric hormones ghrelin and des-acyl ghrelin have been found to be altered in patients treated with antiepileptic drugs. However, it is unknown if these hormones could be modified by other antiepileptic treatments, such as the ketogenic diet. Especially, a reduction in ghrelin levels could be relevant in view of the growth...

The ketogenic diet (KD) is increasingly used to treat epilepsy refractory to antiepileptic drugs and other neurological disorders. In animal models, the KD was found to increase the threshold to seizures induced by different convulsive stimulations. However, in models in which suprathreshold stimuli were used, a paradoxical seizure worsening was co...

Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone s...

Ghrelin, des-acyl ghrelin and other related peptides possess anticonvulsant activities. Although ghrelin and cognate peptides were shown to physiologically regulate only the ghrelin receptor, some of them were pharmacologically proved to activate the peroxisome proliferator-activated receptor gamma (PPARγ) through stimulation of the scavenger recep...

Patients affected by protocadherin 19 (PCDH19)–female limited epilepsy (PCDH19-FE) present a remarkable reduction in allopregnanolone blood levels. However, no information is available on other neuroactive steroids and the steroidogenic response to hormonal stimulation. For this reason, we evaluated allopregnanolone, pregnanolone, and pregnenolone...

VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF 556−576) has raised...

The 6-Hz corneal stimulation test is used to screen novel antiepileptic molecules to overcome the problem of drug refractoriness. Although recognized as a standard test, it has been evaluated only recently in the attempt to characterize the putative neuronal networks involved in seizures caused by corneal stimulation. In particular, by recording fr...