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M F Ghilardi

Publications and source records attributed to M F Ghilardi.

17 recordsLinked to original sources
PubMed1991

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates.

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

Acetylcarnitine↗
PubMed1990

Mapping of event-related potentials to auditory and visual odd-ball paradigms.

This paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects, patients with Alzheimer's disease (AD), progressive supranuclear palsy, confusional states, and in subjects with homonymous hemianopsia. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, the topographical distribution of all ERP components is described in detail. In 45% of AD patients, ERPs were normal; in 35%, although present, ERP components were delayed, while in the other 20% the N2 and P3 peaks could not be recorded. In patients with progressive supranuclear palsy, the normal ERP sequence was not identified. Our findings in normals and in hemianopic patients suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, SW should have different origins.

Acoustic Stimulation↗
PubMed1990

Attenuation of the early anterior negativity of median nerve somatosensory evoked potential in the MPTP-treated monkey.

Median nerve somatosensory evoked potentials (SEP) were recorded in 7 Cynomolgus monkeys, before and after the administration of N-Methyl 1,4 Phenyl 1,2,3,6 tetrahydropiridine (MPTP), a neurotoxin which induces a parkinsonian syndrome in primates. Following MPTP administration, the amplitude of the negative component recorded at 15 ms over the frontal derivations (N15) decreased by 70% or more. This amplitude reduction was not modified by administration of dopamine precursors. These findings shed light on recent findings in human parkinsonian patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

The effect of intraocular 6-hydroxydopamine on retinal processing of primates.

In previous studies, we showed that in the monkey, systemically administered N-methyl, 4-phenyl, 1-2-3-6 tetrahydropyridine (MPTP) produces a chronic parkinsonian syndrome accompanied by spatial frequency-dependent abnormalities in both the pattern electroretinogram and visual evoked potential. We describe the effect of intravitreally administered 6-hydroxydopamine (6-OH-DA) on the pattern electroretinogram and pattern visual evoked potential of 3 aphakic monkeys. Because of the aphake condition, several complexities of intravitreal injection of 6-OH-DA could be avoided. Nevertheless, following 6-OH-DA treatment, both the phase and the amplitude of pattern electroretinogram and pattern visual evoked potential became abnormal. This abnormality was most pronounced for the higher spatial frequencies (2.5 and 3.5 cycles per degree), whereas lower spatial frequencies (0.5 and 1.2 cycles per degree) were less impaired. The effects of systemically administered MPTP on pattern electroretinogram and pattern visual evoked potential are similar to the effects of intravitreal injections of 6-OH-DA, suggesting that a retinal catecholaminergic system plays an important role in pattern vision of primates.

Animals↗
PubMed1988

Systemic 1-methyl,4-phenyl,1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates.

Following MPTP administration, 4 Cynomolgus monkeys developed a parkinsonian syndrome, accompanied by specific changes of both pattern visual evoked potential and electroretinogram. Retinal dopamine and dihydroxyphenylacetic acid contents were measured in the 4 MPTP-treated monkeys and in 3 normal monkeys. Dopamine and dihydroxyphenylacetic acid levels were significantly lower in the retinas of the MPTP-treated animals (p less than 0.001), suggesting that dopamine has a specific function in the visual system of primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Spatial frequency-dependent abnormalities of the pattern electroretinogram and visual evoked potentials in a parkinsonian monkey model.

The pattern visual evoked potential (PVEP) and pattern electroretinogram (PERG) were studied in 5 cynomolgus monkeys before and during the development of a parkinsonian syndrome induced by MPTP. The stimuli were vertical bars of four spatial frequencies (0.5, 1.2, 2.5 and 3.5 cycles/degree (cpd) modulated at temporal rates of 1, 4, 6, and 8 Hz. Following MPTP administration, all monkeys developed parkinsonian signs accompanied by changes in the amplitude and latency of the PVEP and PERG. Sinemet L-dopat carbi olopa administration produced temporary recovery of both PVEP and PERG. Two of the monkeys were followed for a prolonged period: 30-40 days after MPTP, the parkinsonian signs showed partial recovery; the PVEP latency and amplitude to 2.5 and 3.5 cpd stimuli and the latency to 1.2 cpd showed improvement but remained abnormal. The latencies of PERGs were normal, but the amplitudes were significantly reduced when stimuli of 2.5 and 3.5 cpd were used. Both PVEP and PERG to 0.5 cpd stimuli returned to normal. No further modifications were seen in the recordings performed 6 months and 1 year later. This study demonstrates (1) that spatial frequency-dependent electrophysiological abnormalities occur in the MPTP-treated monkey, a result previously found in human Parkinson's disease, and (2) that dopamine has a specific function in neurotransmission in the visual system of primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1987

Scalp distribution of pattern visual evoked potentials in normal and hemianopic monkeys.

We examined the hemispheric distribution of the pattern visual evoked potential in 3 Cynomolgus monkeys, before and after right optic tractotomy or left occipital lobectomy. The stimuli were vertical gratings of 4 spatial frequencies, presented using counterphase and on-off modulation at 1 and 8 Hz. In the normal monkey, the amplitude and latency of the PVEPs elicited by 1 Hz stimulation were similar across all electrode sites. While no differences were found in the phase of the PVEP elicited by 8 Hz stimulation across the different derivations, PVEP amplitude generally decreased over the lateral electrodes. Once experimental hemianopia was created, PVEPs recorded over the midline and the intact hemisphere were normal. However, partially polarity-inverted PVEPs of smaller amplitude were recorded over the deafferented hemisphere. In addition, the interhemispheric phase difference became more prominent in the PVEP recorded over the deafferented hemisphere as the spatial frequency was increased.

Animals↗
PubMed1987

Effect of levo-acetylcarnitine on P300-like potentials of the normal monkey.

Endogenous components of evoked potentials resembling P300 in human beings were sequentially studied in four cynomolgus monkeys (Macaca fascicularis using an auditory "oddball" paradigm, after classical conditioning training. When robust P300-like signals were obtained, each animal underwent further recording sessions in which a placebo, L-carnitine or L-acetylcarnitine (LAC) was injected. Only LAC induced an amplitude increment of P300 waves in all the animals and a latency decrement in two animals. Furthermore a transient effect with amplitude reduction on the primary cortical auditory evoked potentials (AEP) both to rare and frequent tones was also recorded in all the animals. This effect resembled the AEP amplitude reduction induced by physostigmine administration. The findings suggest an effect of LAC on normal processes accompanying cognition.

Acetylcarnitine↗
PubMed1986

P300-like potentials in the normal monkey using classical conditioning and an auditory 'oddball' paradigm.

Endogenous components of evoked potentials resembling P300 in humans were sequentially studied in 3 cynomolgus monkeys (Macaca fascicularis) using an auditory 'oddball' paradigm. The two different auditory stimuli were 500 Hz and 4000 Hz tones, designated as the 'frequent' and 'rare' stimuli, respectively. The probability of 'rare' tone presentation was initially 0.2. We further used probabilities of 0.1, 0.3 and 0.5. The 'rare' stimulus was reinforced by electrical stimulation, which followed the onset of the high tone by 700 msec. After 3-5 training sessions, a late positive wave was observed following the 'rare' tone. The latency of this P300-like signal was 314 +/- 16.2 msec, and the amplitude was 23.6 +/- 3.14 microV. The amplitude of this potential was modified by changes in stimulus presentation probability and by withholding reinforcement.

Animals↗
PubMed1986

Visual evoked potentials in parkinsonism and dopamine blockade reveal a stimulus-dependent dopamine function in humans.

VEPs were recorded with three different spatial frequencies of stimulation in patients affected by idiopathic Parkinsonism and by Parkinsonian syndromes. The detection of VEP abnormalities in Parkinson's disease was dependent on the spatial frequency of the visual stimulus (a vertical square wave grating). The VEP latency was normal in Parkinsonian syndrome patients (except in one patient affected by familial Parkinsonism). Dopamine precursor therapy differently reduced the VEP latency, depending on the spatial frequency of the visual stimulus. These findings suggest that the dopaminergic mechanism involved in the generation of VEP delays is sensitive to stimulus spatial frequency. The study of VEPs before and after the administration of haloperidol confirmed this hypothesis. VEP latency did not correlate with the major clinical symptoms of Parkinson's disease and could not predict the results of chronic dopaminergic therapy.

Adult↗
PubMedDate not supplied

Reproducibility of cardiovascular autonomic tests in diabetics with and without autonomic dysfunction and in normal controls.

The present study evaluates the reproducibility of five cardiovascular reflex tests, deep breathing (DB), Valsalva maneuver (VM), sustained hand-grip (SHG), postural hypotension (PH) and lying to standing (LS) in normal subjects and in insulin dependent (type I) diabetic patients. The study was carried out in 10 normal subjects, in 10 diabetics with autonomic neuropathy and in 10 diabetics without autonomic neuropathy. The five cardiovascular reflex tests were performed five times on five consecutive days by the same investigator and in identical basal conditions. The intraindividual variability of DB, LS and VM was significantly reduced in diabetics with autonomic neuropathy compared with normal controls, but there was no difference between diabetics without neuropathy and normal controls. The intraindividual variability of PH was significantly increased in diabetics with autonomic neuropathy compared with diabetics without autonomic neuropathy and with normal controls. There was no difference among the three groups in the reproducibility of SHG. In normal subjects the intraindividual variability only exceptionally produced a shift from normal to abnormal values or vice versa; in diabetics with autonomic neuropathy this shift was more frequent.

Adult↗
PubMedDate not supplied

Alterations in event-related potentials (ERPs) of MPTP-treated monkeys.

Using an auditory 'oddball' paradigm and classical conditioning, we have studied auditory evoked potentials (AEPs) and P300-like potentials in monkeys pre- and post-MPTP treatment. Free-field acoustic stimuli were 500 Hz and 4000 Hz tones, which were designated as the 'frequent' and 'rare' conditions, respectively. The 4000 Hz stimuli were reinforced with mild somatosensory electrical stimulation. During the first few weeks following 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) administration, all monkeys gradually developed a parkinsonian syndrome, which partially, but not completely improved within 30-40 days in 2 animals. The amplitudes of the AEP were initially significantly decreased, but progressively returned to pretreatment magnitudes in the 2 monkeys which partially recovered. P300-like potentials were initially abolished in all animals; however, 30-40 days later P300 spontaneously re-emerged in the same 2 monkeys. Latencies of both of these signals were unaffected by MPTP. Acute administration of dopamine precursor during the first phase of neurotoxicity partially and temporarily improved depressed AEP amplitudes, but did not restore absent P300-like potentials. The relevance of these results for Parkinson's disease is discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

N70 and P100 can be independently affected in multiple sclerosis.

We have studied the relationship between N70 and P100 of the pattern visual evoked potential in 98 patients with multiple sclerosis and in 59 controls. In patients with multiple sclerosis, P100 was either absent or had prolonged latency in 121 eyes (61.7%), while N70 was absent or prolonged in 97 eyes (49.5%). The total number of eyes with either N70 and/or P100 abnormalities was 137 (69.9%). Eighty eyes (40.8%) had abnormal latency of both P100 and N70, while 41 eyes showed P100 delays without corresponding N70 changes. Seventeen eyes had abnormal N70, but normal P100 latency. N70 and P100 appear to be more often absent in the definite rather than in the possible multiple sclerosis group. These data show that N70 and P100 can be independently affected in patients with MS.

Adolescent↗
PubMedDate not supplied

Visual 'cognitive' evoked potentials in the behaving monkey.

Using a visual 'oddball' paradigm we studied ERPs in monkeys trained in a 'go' 'no-go' discrimination task. The stimuli were 2.5 cpd sinusoidal gratings differing only in orientation (0 degrees or 25 degrees). Monkeys released a lever during 1 of 2 response windows (RW), 480-1762 or 740-1672 msec, following target stimulus onset. Target stimulus presentation probabilities were 1.0, 0.5 and 0.3. The primary evoked potentials recorded to either the target or non-target stimulus were similar in all monkeys. P3 signals progressively emerged in the monkeys only to the target stimulus. P3 recorded at Cz, P3, and P4 had similar mean latencies and amplitudes. Eye movements showed no relationship to P3 potentials. Neither the primary visual potentials nor P3 changed significantly as a function of RW. P3 amplitude was inversely related to target probability. When the target stimulus was presented 100% of the time (P = 1.0) P3 disappeared over 4-5 blocks of trials, while the primary evoked potentials remained consistent.

Animals↗