25 results on '"Massimiliano Braga"'
Search Results
2. Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke
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Valeria De Giuli, Mario Grassi, Michele Besana, Marialuisa Zedde, Andrea Zini, Corrado Lodigiani, Simona Marcheselli, Anna Cavallini, Giuseppe Micieli, Maurizia Rasura, Maria Luisa DeLodovici, Giampaolo Tomelleri, Nicoletta Checcarelli, Alberto Chiti, Elisa Giorli, Massimo Del Sette, Lucia Tancredi, Antonella Toriello, Massimiliano Braga, Andrea Morotti, Debora Pezzini, Martina Locatelli, Valentina Mazzoleni, Sonia Bonacina, Massimo Gamba, Mauro Magoni, Rosalba Patella, Alessandra Spalloni, Anna Maria Simone, Rosario Pascarella, Sandro Beretta, Alessandro Padovani, Roberto Gasparotti, Alessandro Pezzini, Nicola Gilberti, Paola Ferrazzi, Elena Banfi, Luca Librè, Elisabetta Traverso, Erika Schirinzi, Federico Carimati, Manuel Cappellari, Giampiero Locatelli, Laura Demelas, Davide Ferrario, Alessandra Persico, Giovanni Orlandi, Manuela Napoli, Claudio Moratti, and Mario Guidotti
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Adult ,Male ,medicine.medical_specialty ,Brain Ischemia ,Brain ischemia ,White matter ,Young Adult ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Young adult ,Stroke ,Acute ischemic stroke ,Aged ,Ischemic Stroke ,Subclinical infection ,Advanced and Specialized Nursing ,business.industry ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Cerebral Small Vessel Diseases ,Cardiology ,Brain lesions ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. Methods: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. Results: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30–3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20–3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22–4.32]). After a median follow-up of 36.0 months (25th–75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17–3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20–3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36–4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42–4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. Conclusions: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.
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- 2022
3. Long-term outcome of cervical artery dissection
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Carlo Gandolfo, Maurizia Rasura, Alessandro Padovani, Maurizio Paciaroni, Marina Mannino, Sandro Sanguigni, Maurizio Melis, Maria Sessa, Giorgio Silvestrelli, Massimo Del Sette, Sonia Bonacina, Mauro Magoni, Paolo Cerrato, Alessandro Adami, Andrea Morotti, Maria Vittoria Calloni, Alessandro Pezzini, Carla Zanferrari, Patrizia Nencini, Giuseppe Micieli, Manuel Cappellari, Mario Grassi, Martina Locatelli, Marialuisa Zedde, Giuseppina Calabrese, Valeria Bignamini, Claudio Baracchini, Simona Marcheselli, Valeria Terruso, Anna Bersano, Paolo La Spina, Rita Bella, Eugenio Magni, Elisa Giorli, Corrado Lodigiani, Andrea Zini, Rocco Salvatore Calabrò, Enrico Maria Lotti, Fabio Melis, Anna Cavallini, Cristiano Azzini, Maria Luisa DeLodovici, Carlo Dallocchio, Rossana Tassi, Massimiliano Braga, and Mauro Gentile
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Pediatrics ,medicine.medical_specialty ,Longitudinal study ,Subarachnoid hemorrhage ,Cervical Artery ,Dermatology ,Cervical artery dissection ,arteries ,03 medical and health sciences ,Stroke in young adults ,0302 clinical medicine ,cohort studies ,multicenter studies as topic ,risk factors ,Medicine ,030212 general & internal medicine ,cervical artery dissection ,outcome ,stroke in young adults ,adolescent ,dissection ,female ,humans ,Italy ,stroke ,vertebral artery dissection ,Risk factor ,Stroke ,Outcome ,Neuroradiology ,business.industry ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Dissection ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Cohort study - Abstract
Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.
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- 2020
4. History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS)
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Rosalba Patella, Nicoletta Checcarelli, Valeria De Giuli, Corrado Lodigiani, Massimiliano Braga, Andrea Zini, Lucia Tancredi, Antonella Toriello, Alberto Chiti, Anna Cavallini, Marialuisa Zedde, Michele Besana, Massimo Gamba, Alessandro Padovani, Elisa Giorli, Giampaolo Tomelleri, Rosario Pascarella, Anna Maria Simone, Massimo Del Sette, Loris Poli, Enrico Fainardi, Roberto Gasparotti, Maria Luisa DeLodovici, Filomena Caria, Mario Grassi, A. Spalloni, Simona Marcheselli, Andrea Morotti, Alessandro Pezzini, Maurizia Rasura, Sandro Beretta, and Giuseppe Micieli
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lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,Ischemia ,030204 cardiovascular system & hematology ,Brain ischemia ,03 medical and health sciences ,Animal data ,0302 clinical medicine ,Interquartile range ,Internal medicine ,medicine ,cardiovascular diseases ,Stroke ,business.industry ,medicine.disease ,Migraine with aura ,Risk factors ,Migraine ,lcsh:RC666-701 ,Cortical spreading depression ,brain ischemia ,cortical spreading depression ,migraine disorders ,risk factors ,stroke ,Migraine disorders ,Cardiology ,Original Article ,Neurology (clinical) ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Brain ischemia Cortical spreading depression Migraine disorders Risk factors Stroke - Abstract
Background and PURPOSE Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P
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- 2019
5. Photosensitive organic insulator photo-cell monitoring through advanced macro inspection
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Matteo Salamone, Massimiliano Braga, Francesco Ferrario, Umberto Iessi, Paolo Parisi, Paolo Canestrari, Andrea Corno, Alessio Pescalli, Thomas Groos, Annalisa Bordogna, and Parikshit Sharma
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Passivation ,business.industry ,Computer science ,Rework ,Microelectronics ,Process control ,Photodetector ,Insulator (electricity) ,Macro ,business ,Chip ,Process engineering - Abstract
In microelectronic device manufacturing, photosensitive organic insulators (POIs) are widely used during passivation steps to protect and preserve the chips from damage due to subsequent processes and from the external environment. To ensure high performance and to maintain chip quality, a well-controlled POI lithography process and corresponding defectivity monitoring are needed. In this work, we present an automated method developed by STMicroelectronics and KLA for POI defectivity and process control employing a KLA 8 Series inspection system with illumination in the visible range. The highly sensitive macro inspection tool with dedicated analysis approaches and solutions successfully enabled the detection of the principal defects of interest, the identification of defectivity root causes through automatic classification and review, and the evaluation of the layer thickness and uniformity through reflected intensity heatmaps. For several months, this protocol has been applied to the production environment, proving to be effective in detecting even small deviations from the standard process. Here, we present some promising results obtained with this strategy, highlighting the benefits in terms of rework reduction and improved equipment management.
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- 2020
6. Neurological disorders associated with COVID-19 infection: An Italian multi-center cohort study (NEURO-COVID)
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Simone Beretta, Andrea Zini, Elisa Bianchi, Viviana Cristillo, Alberto Priori, Giacomo Sferruzza, Massimiliano Braga, Maria Cotelli, Ludovico Ciolli, Matteo Pardini, Francesco Bax, Maria Sessa, Gioacchino Tedeschi, Andrea Pilotto, Susanna Guttmann, Angelo Schenone, Mario Orrico, Marinella Turla, Stefania Maffei, Lucia Tancredi, Martina Viganò, Guido Primiano, Ettore Beghi, Luana Benedetti, Valeria De Giuli, Stefano Meletti, Beatrice Viti, Emanuele Bartolini, Gian Luigi Gigli, Carlo Morotti Colleoni, Massimo Filippi, Narghes Calcagno, Prabha Cristina Ranchicchio, Sandro Beretta, Edoardo Barvas, Vincenzo Silani, Pasquale Palumbo, Bruno Censori, Carlo Ferrarese, Alessandro Padovani, Francesca Trogu, Pietro Cortelli, Stefano Caproni, Serenella Servidei, and Mauro Gentile
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Pediatrics ,medicine.medical_specialty ,Neurology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Medicine ,Center (algebra and category theory) ,Neurology (clinical) ,business ,Article ,Cohort study - Published
- 2021
7. The Neurologist in the Emergency Room: Prospective Study of the Neurological Emergency Group in Lombardia
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Elisa Candeloro, Marco Mauri, Maria Vittoria Calloni, MariaLuisa Delodovici, Lucia Tancredi, Bruno Censori, Franca Mazzucchelli, Giuseppina Borutti, Maria Sessa, Elena Ballabio, Chiara Scaccabarozzi, Megi Meneri, Elisabetta Forapani, Claudio De Piazza, Laura Fusi, Marco Gallazzi, Ignazio Santilli, and Massimiliano Braga
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medicine.medical_specialty ,Group (periodic table) ,business.industry ,Emergency medicine ,Medicine ,business ,Prospective cohort study - Published
- 2019
8. Italian symptomatic intracranial atherosclerosis study (ISIDE)
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Stefano Ricci, Agnese Tonon, Claudio Baracchini, Rita Bella, Massimo Del Sette, Gian Paolo Anzola, Massimiliano Braga, Carla Zanferrari, Marialuisa Zedde, Pietro Caliandro, Marina Diomedi, Giorgio Meneghetti, Silvia Cenciarelli, and Carlo Gandolfo
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Male ,medicine.medical_specialty ,Symptomatic intracranial atherosclerosis ,Ultrasonography, Doppler, Transcranial ,Dermatology ,030204 cardiovascular system & hematology ,Magnetic resonance angiography ,03 medical and health sciences ,0302 clinical medicine ,Ultrasound ,medicine ,Humans ,Longitudinal Studies ,ICAS ,Stroke ,Aged ,Neuroradiology ,Computed tomography angiography ,Aged, 80 and over ,medicine.diagnostic_test ,Cerebral infarction ,business.industry ,General Medicine ,Odds ratio ,Middle Aged ,Intracranial Arteriosclerosis ,medicine.disease ,Transcranial Doppler ,Psychiatry and Mental health ,Stenosis ,Italy ,Multivariate Analysis ,cardiovascular system ,Settore MED/26 - Neurologia ,Female ,Neurology (clinical) ,Radiology ,business ,030217 neurology & neurosurgery - Abstract
There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of a ≥50 % stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6 %) men, with a mean age of 71.2 ± 13.3 years. ICAS was recorded in 99 patients (8.7 % of the whole sample, 8.9 % among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5 %). After adjusting for potential confounders, multivariate analysis identified carotid/vertebral ≥50 % stenosis [odds ratio (OR) 2.59, 95 % (confidence interval) CI 1.77-6.33; P = 0.02] and hypercholesterolemia (OR 1.38, 95 % CI 1.02-1.89; P = 0.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9 % of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases with ≥50 % cervical vessel stenoses.
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- 2016
9. Persistent Interictal Musical Hallucination in a Patient With Mesial Temporal Sclerosis-Related Epilepsy: First Case Report and Etiopathological Hypothesis
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Sandro Beretta, Massimiliano Braga, Massimo Pederzoli, Marcella Vedovello, and Paolo Borelli
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medicine.medical_specialty ,Hallucinations ,Hearing loss ,Cognitive Neuroscience ,Audiology ,050105 experimental psychology ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Charles Bonnet syndrome ,medicine ,Humans ,0501 psychology and cognitive sciences ,Ictal ,Psychiatry ,Depression (differential diagnoses) ,Temporal cortex ,Sclerosis ,business.industry ,05 social sciences ,General Medicine ,Middle Aged ,medicine.disease ,Temporal Lobe ,Psychiatry and Mental health ,Neuropsychology and Physiological Psychology ,Epilepsy, Temporal Lobe ,Schizophrenia ,Antidepressant ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Music - Abstract
Musical hallucination is a disorder of complex sound processing of instrumental music, songs, choirs, chants, etc. The underlying pathologies include moderate to severe acquired hearing loss (the auditory equivalent of Charles Bonnet syndrome), psychiatric illnesses (depression, schizophrenia), drug intoxication (benzodiazepines, salicylate, pentoxifylline, propranolol), traumatic lesions along the acoustic pathways, and epilepsy. The hallucinations are most likely to begin late in life; 70% of patients are women. Musical hallucination has no known specific therapy. Treating the underlying cause is the most effective approach; neuroleptic and antidepressant medications have only rarely succeeded.Musical hallucination in epilepsy typically presents as simple partial seizures originating in the lateral temporal cortex. To our knowledge, no formal report of musical hallucination in the interictal state has been published before. In contrast, other interictal psychotic features are a relatively common complication, especially in patients with long-standing drug-resistant epilepsy.We describe a 62-year-old woman with a long history of mesial temporal lobe epilepsy whose musical hallucination was solely interictal. We speculate on the possible link between temporal epilepsy and her hallucination. We hypothesize that, as a result of her epileptic activity-induced damage, an imbalance developed between the excitatory and inhibitory projections connecting the mesial temporal cortex to the other auditory structures. These structures may have generated hyperactivity in the lateral temporal cortex through a "release" mechanism that eventually resulted in musical hallucination.
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- 2016
10. A practical definition of minor stroke
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Simona Sacco, Massimiliano Braga, Angelo A. Bignamini, Vittorio Crespi, Sandro Beretta, and Antonio Carolei
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medicine.medical_specialty ,Neurology ,Databases, Factual ,business.industry ,MEDLINE ,Minor stroke ,Dermatology ,General Medicine ,medicine.disease ,Patient Discharge ,Stroke ,Psychiatry and Mental health ,Patient Admission ,Modified Rankin Scale ,Physical therapy ,Humans ,Medicine ,Observational study ,Neurology (clinical) ,Neurosurgery ,business ,Neuroradiology - Abstract
It is generally assumed that minor stroke (MS) is an ischemic stroke with a short-term, good functional outcome. However, no clear definition of MS exists. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) are still the most accredited standards, but scores and timing of the assessment are not homogeneous. As suggested by a qualified sample of Italian neurologists, the index parameter chosen in our analysis was mRS at the time of hospital discharge. The database of the SIRIO study (a large observational study of 2,573 patients with stroke admitted in Italian hospitals in 2005) was used to identify an mRS threshold to define MS. Reference was made to outcome markers such as rate of discharge to home, 1-year disability and 1-year mortality. The rate of discharge progressively decreased with increase in mRS, while the rates of 1-year mortality and disability progressively increased. Our proposal is one of defining a stroke "minor" when the rate of discharge to home is above the SIRIO database overall value and the 1-year mortality and disability is below the respective overall values. This definition is consistent with a score ≤2 on the mRS.
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- 2012
11. Early Onset of Severe Familial Amyotrophic Lateral Sclerosis with a SOD-1 Mutation: Potential Impact of CNTF as a Candidate Modifier Gene
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Bertram Müller-Myhsok, Bettina Holtmann, Michael Sendtner, Massimiliano Braga, Tiemo Grimm, Ralf Giess, and Klaus V. Toyka
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Adult ,Male ,medicine.medical_specialty ,Genotype ,Locus (genetics) ,Ciliary neurotrophic factor ,Exon ,Mice ,Degenerative disease ,Quantitative Trait, Heritable ,Superoxide Dismutase-1 ,Genetic linkage ,Internal medicine ,medicine ,Genetics ,Animals ,Humans ,Genetics(clinical) ,Ciliary Neurotrophic Factor ,Amyotrophic lateral sclerosis ,Allele ,Age of Onset ,Gene ,Genetics (clinical) ,Genes, Dominant ,Motor Neurons ,biology ,Base Sequence ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Genetic Variation ,Articles ,Middle Aged ,medicine.disease ,Pedigree ,Disease Models, Animal ,Endocrinology ,Mutation ,biology.protein ,Female - Abstract
Mutations in the copper/zinc superoxide dismutase 1 (SOD-1) gene are found in approximately 20% of patients with familial amyotrophic lateral sclerosis (FALS), or amyotrophic lateral sclerosis 1. Here we describe a 25-year-old male patient who died from FALS after a rapid disease course of 11 mo. Sequencing of the SOD-1 gene revealed a heterozygous T--G exchange at position 1513 within exon 5, coding for a V--G substitution at position 148 of the mature protein. Genetic analysis of this family revealed the same mutation in both his healthy 35-year-old sister and his mother, who did not develop the disease before age 54 years. Screening for candidate modifier genes that might be responsible for the early onset and severe course of the disease in the 25-year-old patient revealed an additional homozygous mutation of the CNTF gene not found in his yet unaffected sister. hSOD-1G93A mice were crossbred with CNTF(-/-) mice and were investigated with respect to disease onset and duration, to test the hypothesis that CNTF acts as a candidate modifier gene in FALS with mutations in the SOD-1 gene. Such hSOD-1G93A/CNTF-deficient mice develop motoneuron disease at a significantly earlier stage than hSOD-1G93A/CNTF-wild-type mice. Linkage analysis revealed that the SOD-1 gene was solely responsible for the disease. However, disease onset as a quantitative trait was regulated by the allelic constitution at the CNTF locus. In addition, patients with sporadic amyotrophic lateral sclerosis who had a homozygous CNTF gene defect showed significantly earlier disease onset but did not show a significant difference in disease duration. Thus, we conclude that CNTF acts as a modifier gene that leads to early onset of disease in patients with FALS who have SOD-1 mutations, in patients with sporadic amyotrophic lateral sclerosis, and in the hSOD-1G93A mouse model.
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- 2002
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12. Agenesis of the Right Internal Carotid Artery and Klippel-Feil Syndrome
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Massimiliano Braga, Vittorio Crespi, Guido Arpaia, M. Ferrarini, Sandro Beretta, Paola Canovaro, and Massimo Pederzoli
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medicine.medical_specialty ,Ticlopidine ,Vertebral artery dissection ,Klippel–Feil syndrome ,Magnetic resonance angiography ,medicine.artery ,medicine ,Basilar artery ,Humans ,Abnormalities, Multiple ,Orthopedics and Sports Medicine ,medicine.diagnostic_test ,business.industry ,Brain ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Ischemic Attack, Transient ,Klippel-Feil Syndrome ,Agenesis ,Trigeminal artery ,Female ,Neurology (clinical) ,Radiology ,business ,Carotid Artery, Internal ,Magnetic Resonance Angiography ,Congenital disorder ,Cervical vertebrae - Abstract
Study design Case report. Objective To describe the case of a Klippel-Feil anomaly associated with carotid agenesis. Summary of background data Klippel-Feil anomaly is a spinal malformation characterized by fusion of the cervical vertebrae. Four subtypes have been identified for this congenital disorder with different severity of vertebral fusion and different extra-axial anomalies. Most cases are sporadic, although autosomal dominant and autosomal recessive cases are recognized. It can cause neurologic disorders and is associated to vascular abnormalities. However, agenesis of internal carotid and Klippel-Feil syndrome is an unusual association. Methods A 49-year-old woman came to our attention for recurrent transitory ischemic attacks presenting with weakness of left limbs associated with sensory abnormalities. Neurologic examination revealed mild left limb weakness and tactile hypoesthesia. Results Brain magnetic resonance (MR) and MR angiography demonstrated absence of the right internal carotid and the middle right cerebral artery was filled from the basilar artery. Fusion of vertebral bodies was documented at MR and confirmed at spinal CT scan. The day after the admission the neurologic examination became normal. Ticlopidine was then started. Conclusion Literature of vascular abnormalities in association with Klippel-Feil syndrome takes the form of anecdotal reports. Aortic coarctation, vertebral artery dissection, aneurysms, persistent trigeminal artery, and abnormal origin of internal carotid are described. An unusual association of carotid internal agenesis and Klippel-Feil syndrome is reported with a literature review.
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- 2009
13. Myelinolytic lesions in spinal cord of cobalamin‐deficient rats are TNF‐α‐mediated
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Mariarosaria Miloso, Giuseppe Scalabrino, Giovanni Tredici, Giulio Pravettoni, Alberto Morabito, Gabriella Nicolini, Massimiliano Braga, and Francesca R. Buccellato
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Male ,medicine.medical_specialty ,Pathology ,Biochemistry ,Cobalamin ,Rats, Sprague-Dawley ,White matter ,Myelin ,chemistry.chemical_compound ,Gastrectomy ,Transforming Growth Factor beta ,Internal medicine ,Edema ,Genetics ,medicine ,Animals ,Molecular Biology ,Microinjection ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Chemistry ,Vitamin B 12 Deficiency ,Myelitis ,Spinal cord ,Rats ,medicine.anatomical_structure ,Endocrinology ,Spinal Cord ,Subacute Combined Degeneration ,Tumor necrosis factor alpha ,medicine.symptom ,Biotechnology - Abstract
Repeated intracerebroventricular (i.c.v.)microinjection of tumor necrosis factor-alpha (TNF-alpha) into normal rats causes intramyelin and interstitial edema in the white matter of the spinal cord (SC). This response is identical to that observed in the SC white matter of rats made cobalamin (Cbl) deficient by total gastrectomy (TG). Immunoblot analysis showed that: 1) the level of the biologically active form of the TNF-alpha protein (17 kDa) is higher in the SC of totally gastrectomized (TGX) rats 2 months after TG, i.e., at the postoperative time when edema is observed; 2) SC levels of TNF-alpha protein (17 kDa) in 2-mo-TGX-, Cbl-treated rats are reduced to control. Repeated i.c.v. microinjections of anti-TNF-alpha antibodies, transforming growth factor-beta1 (TGF-beta1) or interleukin-6 (IL-6) into TGX rats, begun shortly after TG, substantially reduced both intramyelin and interstitial edema in the SC white matter. This study provides the first evidence that the hallmark myelin damage of Cbl-deficient central neuropathy, which is a pure myelinolytic disease, is not caused directly by the withdrawal of the vitamin itself, but reflects enhanced production of the biologically active form of TNF-alpha by SC cells. This study thus supports the view that TGF-beta1 and IL-6 may act as neuroprotective agents in Cbl deficiency central neuropathy.
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- 1999
14. Immunomagnetic isolation of human developing motor neurons
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Christiana Bonifati, Antonia Ratti, Mauro Buscaglia, Andrea Brioschi, Feng C. Zhou, Antonio Pizzuti, Vincenzo Silani, Andrea Ciammola, Guglielmo Scarlato, and Massimiliano Braga
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Motor Neurons ,Immunomagnetic Separation ,General Neuroscience ,Central nervous system ,Reproducibility of Results ,Motor neuron ,Biology ,Immunomagnetic separation ,Spinal cord ,Immunohistochemistry ,Choline acetyltransferase ,Molecular biology ,In vitro ,Chemically defined medium ,medicine.anatomical_structure ,Spinal Cord ,Cell culture ,Immunology ,medicine ,Humans ,Cells, Cultured - Abstract
HUMAN motor neuron (MN) isolation provides a critical tool to study neurophysiological properties and the effects of molecules of clinical relevance on isolated neurons. We developed an immunomagnetic separation technique based on specific MN antigen recognition for nerve growth factor receptor (p 75-NGFR ). We cultured an average of 250 000 cells from the anterior horns of a single cord (four specimens at postconception Weeks 6.0, 7.2, 8.0, and 8.3). At day 7 in vitro (DIV), choline acetyltransferase (ChAT) and/or p 75-NGFR -expressing cells (MNs) represented 72 ± 2% of the total growing cells. MNs survived for at least 4 weeks in biochemically defined medium. The immunomagnetic separation method has been demonstrated to be effective, reproducible, and quantitative for separation of MNs.
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- 1998
15. Reasons for hospitalization in Parkinson's disease: a case-control study
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Francesca Beretta, Vittorio Crespi, Massimiliano Braga, Massimo Pederzoli, and Angelo Antonini
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Male ,Pediatrics ,medicine.medical_specialty ,Parkinson's disease ,Population ,Disease ,Comorbidity ,Infections ,Patient Admission ,Catchment Area, Health ,Medicine ,Humans ,In patient ,General hospital ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Inpatient care ,business.industry ,Case-control study ,Age Factors ,Parkinson Disease ,Middle Aged ,medicine.disease ,Hospitalization ,Neurology ,Cardiovascular Diseases ,Case-Control Studies ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,Nervous System Diseases ,business - Abstract
Background To characterize reasons for hospital admission, mortality and surgical procedures in patients with Parkinson's disease (PD) compared to controls. Methods The clinical features of all consecutive patients from 2000 to 2007 were reviewed. We identified patients with PD (ICD 9 code 332.0) from a database of our General Hospital (Vimercate) with a catchment's population of 180,000. Data on admitting wards as well as reasons for admission, surgical procedures performed and clinical outcome were collected. Clinical data were compared to an age and sex matched control population admitted in the same period of time. Results The total number of admissions was 367. Mean age was 76.7 years. The mean duration of stay was 9.2 days for controls and 9.7 for PD patients. A comorbid disorder was the cause of admission in 80% of cases and 79% of cases came from the Emergency Room. Infectious diseases, mainly respiratory infections, were more frequent in PD of both sexes, while trauma was significantly higher only in PD men. Percentage of patients treated surgically was similar in both cases and controls. Intrahospital mortality was 6% both in PD and controls. Infectious diseases were more frequent in PD patients while cardiovascular death was more frequent in controls. Conclusions Comorbidity in PD is higher than reported in other reports. In our study PD patients had the same length of hospitalization and intrahospital mortality as controls. The presence of a control population allows to discriminate between general complications of the elderly and specific vulnerabilities of PD patients.
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- 2013
16. Human developing motor neurons as a tool to study ALS
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Antonio Pizzuti, Alessandra Bez, Veronica Cardin, Andrea Botturi, Vincenzo Silani, Guglielmo Scarlato, and Massimiliano Braga
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Nervous system ,Motor Neurons ,Nervous tissue ,Cell ,Amyotrophic Lateral Sclerosis ,Motor neuron ,Biology ,medicine.disease ,Tissue culture ,medicine.anatomical_structure ,medicine ,Humans ,Neurology (clinical) ,DNA microarray ,Amyotrophic lateral sclerosis ,Progenitor cell ,Neuroscience ,Cells, Cultured - Abstract
Defining the basis of the selective cell vulnerability of human motor neurons (hMNs) represents a crucial step in revealing the pathogenesis of amyotrophic lateral sclerosis (ALS). Tissue culture models offer an ideal system for identification of the hMN-specific features at the single cell level. Purified hMNs and astrocytes can today be isolated from the anterior horn of the human embryonic spinal cord. Cultures can be studied at the single cell level using cDNA/mRNA amplification techniques. The effects of molecules affecting hMN survival, neurite extension, and metabolism can be tested in vitro and the expression of selective genes assayed using DNA microarray technology. Crucial information of immediate clinical application for the treatment of patients affected by ALS can be derived after testing the efficacy of candidate pharmaceutical molecules using in vitro cell models. Adult nervous tissue or progenitor cells derived from different regions of the nervous system may be used as an alternative source of human neuronal cells. HMNs in culture, combined with the application of adequate technology, can contribute greatly to identifying the primitive critical events responsible for the cell degeneration observed in ALS, bypassing the intrinsic limitations of the non-human models of the disease.
- Published
- 2001
17. Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats
- Author
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Gabriella Nicolini, Angelo Schenone, Paola Marmiroli, Lucilla Nobbio, Mariarosaria Miloso, Lodovico Frattola, Massimiliano Braga, Giovanni Tredici, Guido Cavaletti, Tredici, G, Braga, M, Nicolini, G, Miloso, M, Marmiroli, P, Schenone, A, Nobbio, L, Frattola, L, and Cavaletti, G
- Subjects
medicine.medical_specialty ,Time Factors ,Peripheral neuropathy ,Spinal ,medicine.medical_treatment ,Neurotoxins ,Wistar ,Neural Conduction ,Neurophysiology ,Pain ,Neuroprotection ,Nerve conduction velocity ,Nerve growth factor ,Developmental Neuroscience ,Internal medicine ,Ganglia, Spinal ,medicine ,Pathology ,Animals ,Humans ,Nerve Growth Factors ,Rats, Wistar ,Cisplatin ,business.industry ,Growth factor ,Neurotoxicity ,medicine.disease ,Sciatic Nerve ,Recombinant Proteins ,Rats ,Endocrinology ,Neurology ,Female ,Toxicity ,Ganglia ,business ,medicine.drug - Abstract
In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. Pathological and morphometrical examinations of the dorsal root ganglia (DRG) and sciatic and saphenous nerves were also performed. rhNGF treatment induced a significant reduction in the CDDP-induced decrease in nerve conduction velocity (P < 0.05), and this was associated with a significant protection against the decrease in somatic (P < 0.05), nuclear (P < 0.05), and nucleolar size (P < 0.01) caused by CDDP treatment. However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity
- Published
- 1999
18. A tentative interpretation of electromyographic regional differences in bulbar- and limb-onset ALS
- Author
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A. Brioschi, Alberto Cappellari, Vincenzo Silani, Sergio Barbieri, Guglielmo Scarlato, and Massimiliano Braga
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Adult ,Male ,Neural Conduction ,Electromyography ,Central nervous system disease ,Degenerative disease ,medicine ,Humans ,In patient ,Amyotrophic lateral sclerosis ,Aged ,Denervation ,medicine.diagnostic_test ,business.industry ,Muscles ,Amyotrophic Lateral Sclerosis ,Anatomy ,Motor neuron ,Middle Aged ,medicine.disease ,body regions ,medicine.anatomical_structure ,Data Interpretation, Statistical ,Female ,Neurology (clinical) ,business ,Regional differences - Abstract
Electromyography (EMG) could be useful in defining regional motor neuron vulnerability in ALS. We performed EMG in 36 sporadic ALS patients (9 with bulbar-onset and 27 with limb-onset symptoms). Active denervation was more frequent in limb than in corresponding paraspinal muscles, in the thoracic paraspinal, and in the bulbo-cervical muscles in patients with bulbar-onset symptoms. These results are consistent with a regional motor neuron vulnerability along with a nerve length-dependent liability.
- Published
- 1999
19. Medical treatment for nocardial brain abscesses
- Author
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Claudio Farina, Sandro Beretta, Massimo Pederzoli, Maria Repaci, Giorgio Casati, M. Ferrarini, P. Bazzi, Massimiliano Braga, and Vittorio Crespi
- Subjects
medicine.medical_specialty ,Neurology ,Medical treatment ,business.industry ,General surgery ,medicine ,Neurology (clinical) ,business ,Surgery ,Neuroradiology - Published
- 2005
20. Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol
- Author
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Guido Cavaletti, Giovanni Tredici, Sara Tazzari, Massimiliano Braga, Cavaletti, G, Tredici, G, Braga, M, and Tazzari, S
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Tail ,Paclitaxel ,Neurotoxins ,Neural Conduction ,Pharmacology ,Developmental Neuroscience ,Reference Values ,Ganglia, Spinal ,Medicine ,Neurotoxin ,Animals ,Reference Value ,Rats, Wistar ,business.industry ,Animal ,Neurotoxicity ,Peripheral Nervous System Diseases ,Peroneal Nerve ,Spinal cord ,medicine.disease ,Sciatic Nerve ,Peripheral ,Rats ,Schwann Cell ,Microscopy, Electron ,medicine.anatomical_structure ,Peripheral neuropathy ,Neurology ,Toxicity ,Systemic administration ,Rat ,Female ,Sciatic nerve ,Schwann Cells ,Peripheral Nervous System Disease ,business ,Neuroscience ,Injections, Intraperitoneal - Abstract
Taxol, a natural extract with antineoplastic properties, is known to be neurotoxic in humans. Its neurotoxicity after systemic administration, however, has never been studied in detail at the morphological level in humans and in animals. In this study we administered taxol intraperitoneally to female Wistar rats and we performed an extended neurophysiological and morphological examination of the peripheral nerves, dorsal root ganglia, spinal rootlets, and spinal cord. The results obtained in this experimental model indicate that taxol induces pathological changes mainly in the peripheral nerves, but they are present also in the ventral and dorsal spinal rootlets and spinal dorsal column fibers. The dorsal root ganglia and spinal cord neurons were, on the contrary, unaffected. The most impressive change induced by systemic taxol administration was intraaxonal neurotubule accumulation. Schwann cells showed signs of "activation" but clear demyelination was not observed. We conclude that with the use of this model it is possible to induce a peripheral neuropathy in the Wistar rat which resembles that reported in humans and which can, therefore, be used to better understand the basic mechanism(s) of taxol toxicity and to evaluate protective strategies in an attempt to reduce it.
- Published
- 1995
21. Neurotrophin Effect On The SH‐SY5Y Human Neuroblastoma (HN) MODEL Of Cddp‐Induced Neurotoxicity
- Author
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Paola Marmiroli, Massimiliano Braga, Mariarosaria Miloso, E Donzelli, A Di Silvestro, Giovanni Tredici, S Galbiati, Gabriella Nicolini, and Guido Cavaletti
- Subjects
SH-SY5Y ,Neurite ,biology ,business.industry ,General Neuroscience ,Cellular differentiation ,Neurotoxicity ,Tropomyosin receptor kinase B ,Pharmacology ,Tropomyosin receptor kinase A ,medicine.disease ,Neuroblastoma ,Immunology ,biology.protein ,Medicine ,Neurology (clinical) ,business ,Neurotrophin - Abstract
Neurotrophins (NGF, BDNF, NT-3, NT-4/5) have several pharmacological effects on adult neurons, and it has been proposed that they may play a role in sustaining the reparative mechanisms following peripheral nerve injuries. In this study we evaluated the effect of recombinant human (rh) neurotrophins (rhNGF, gifted by Boehringer Mannheim, Germany; rhBDNF and rhNT-3 gifted by Amgen Co, USA) on cisplatin (CDDP)-induced neurotoxicity in HN SH-SY5Y neurotoxicity model. The cells were differentiated with RA 10 μM and exposed for 4 hours to 2.5 μg/ml CDDP with 50 ng/ml rhNGF, rhBDNF or rhNT-3. Then the cells were maintained in DMEM, 10 μM RA and 50 ng/ml rhNGF, rhBDNF or rhNT-3 and assessed for neurotoxicity 48, 72 and 96 hours after the first treatment with RA. Cells were considered “differentiated” when their neurite was longer than 50 μm. At each time point the neurite length was measured on at least 200 randomly selected cells/dish and the percentage of differentiated cells per culture was calculated. Exposure of RA-differentiated SH-SY5Y cells to CDDP 2.5 μg/ml induced a reduction of the neurite length and of the percentage of differentiated cells. The co-treatment of RA-differentiated SH-SY5Y neuroblastoma cells with CDDP and rhBDNF restored the neurite length and the percentage of differentiated cells to values similar to those of cells treated with RA 10 μM alone. On the contrary, exposure of RA-differentiated SH-SY5Y neuroblastoma cells to rhNT-3/CDDP combination did not significantly modify the neurite length nor the percentage of differentiated cells in comparison to the cells treated with CDDP alone. The effect of rhNGF was intermediate between that of rhBDNF and the absence of any protection observed with rhNT-3. Our results are in agreement with the observation that RA treatment induces the expression of functional trkB receptors in SH-SY5Y cells, which results in BDNF-mediated neuronal differentiation of SH-SY5Y cells and explains the BDNF neuroprotective effect observed, while trkA receptors are expressed at a lower level and trkC receptors are not expressed even after RA-induced differentiation.
- Published
- 2001
22. Erratum
- Author
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Guido Cavaletti, P. Ciscato, Francesca R. Buccellato, Giovanni Tredici, Massimiliano Braga, Giuseppe Scalabrino, and A. Moggio
- Subjects
medicine.medical_specialty ,chemistry.chemical_compound ,Endocrinology ,Neurology ,chemistry ,business.industry ,Internal medicine ,medicine ,Neurology (clinical) ,medicine.disease ,business ,Polyneuropathy ,Cobalamin - Published
- 1999
23. A sporadic case of amyotrophic lateral sclerosis-parkinsonism
- Author
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Silani, V., Brioschi, A., Bernasconi, S., Rango, M., Bozzali, M., Moggio, M., Prelle, A., Comi, G., Gellera, C., Cappellari, A., Ciammola, A., Massimiliano BRAGA, Pellegrini, G., Checcarelli, N., and Scarlato, G.
24. Motor neurones in culture as a model to study ALS
- Author
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Vincenzo Silani, Veronica Cardin, Massimiliano Braga, Guglielmo Scarlato, and Andrea Ciammola
- Subjects
Cell Survival ,Cell ,Glutamic Acid ,Biology ,Tissue culture ,Superoxide Dismutase-1 ,Cell–cell interaction ,Culture Techniques ,medicine ,Animals ,Humans ,Point Mutation ,Amyotrophic lateral sclerosis ,Motor Neurons ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Motor neuron ,medicine.disease ,In vitro ,Mitochondria ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Neurology ,Cell culture ,Astrocytes ,Calcium ,Neurology (clinical) ,Neuroscience ,Astrocyte - Abstract
Defining the basis of the selective cell vulnerability of motor neurones (MN) represents the key issue in amyotrophic lateral sclerosis (ALS), and tissue culture models are the ideal system for the identification of the MN specific features at the single cell level. Neurone-astrocyte metabolic interactions, which have a critical role in MN through glutamatergic toxicity, have been mostly defined in vitro. Ca++ metabolism, which appears to play a critical role in inducing MN loss in ALS, has been successfully studied using in vitro cell models. Furthermore, primary cultures demonstrated that apoptotic or necrotic death of neurones after injury depends upon the cell energetic status. Superoxide dismutase-1 (SOD-1) mutations were successfully expressed in cultured rodent MNs, providing a critical assay to sequence the molecular processes responsible for MN degeneration due to the identified genetic defect. The recent identification of genes that separate humans from apes further increases the value of the human in vitro models to better understand specific human cellular properties. Purified human MNs and astrocytes can today be obtained from the human embryonic spinal cord anterior horns. Interactions at the single cell level can be dissected using the cDNA amplification techniques. The effects of molecules affecting MN survival, neurite extension, and metabolism can easily be defined in vitro, gaining a critical mass of information of immediate clinical application in the treatment of patients affected by ALS. Understanding the properties of human MNs in vitro represents today a significant and critical tool that can easily be reached after extension of the available knowledge from non-primate to human research. Human MN culture studies can greatly contribute to identifying the primitive critical cellular events responsible for the MN degeneration observed in ALS and to gaining crucial information ¶on new therapeutical agents.
25. Off-treatment course of cisplatin-induced dorsal root ganglia neuronopathy in rats
- Author
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Cavaletti, G., Tredici, G., Marmiroli, P., Fabbrica, D., Massimiliano BRAGA, Cavaletti, G, Tredici, G, Marmiroli, P, Fabbrica, D, and Braga, M
- Subjects
neurotoxicity ,cisplatin ,dorsal root ganglia - Abstract
As yet little is known about the off-treatment course of cisplatin (CDDP) neurotoxicity. In this study we evaluated in the rat how the pathological changes in dorsal root ganglia (DRG) neurons and the electrophysiological alterations in peripheral nerves induced by chronic CDDP administration evolved after drug withdrawal. Twelve female Wistar rats were treated with CDDP and 3 of them were sacrificed 1, 5, 10 and 20 weeks after treatment. The results of the experiment indicated that: 1) the damage induced by sub-lethal doses of CDDP in the DRG neurons is reversible, 2) the first structures to be damaged are the DRG neurons (mostly their nucleoli) and 3) both damage and recovery in the follow-up period involve first the DRG neurons and subsequently the peripheral nerves.
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