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Biomedical subjects

O Kopyov

Publications and source records attributed to O Kopyov.

11 recordsLinked to original sources
PubMed2006

Relation between rotation in the 6-OHDA lesioned rat and dopamine loss in striatal and substantia nigra subregions.

The relation between the rotation response to drug-induced activation of the dopamine (DA) receptor in the rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN) and the loss of DA in subregions of the SN and caudate-putamen (C/PUT) is not clear. Here this relation was examined in 23 rats classified as rotators to amphetamine (5 mg/kg). After their response was characterized in terms of ipsilateral rotation, contralateral rotation, and oral stereotypy in one place, they were divided into high, medium, low, and very low rotators. The loss of DA in each group was visualized on brain sections immunoreacted to tyrosine hydroxylase (TH). The density of the TH label on the side of the lesion was compared to that on the intact side. In the ventral midbrain, the density was determined in the SN subdivided into far lateral, lateral, central, and medial subregions and also in the ventral tegmental area (VTA). In the forebrain, it was determined in the C/PUT subdivided into lateral, central, and medial subregions and also in the nucleus accumbens (ACC). These measurements led to three principal findings. The first was a positive overall correlation between rotation and loss of TH label. The second was a correlation between rotation and penetration of the loss from the lateral subregions into more medial areas. The third was a larger loss in SN and VTA (midbrain) than in C/PUT and ACC (forebrain). These findings show that rotation depended not only on the overall loss of DA but also on its distribution across subregions. The loss in the lateral subregion, always the largest regardless of the rate of rotation, may have been the first step in inducing the motor abnormality, and the loss in the central and medial subregions may have served to enhance the abnormality due to the loss in the lateral subregion.

Amphetamine↗
PubMed2005

Behavioral and anatomical effects of quinolinic acid in the striatum of the hemiparkinsonian rat.

Parkinson's disease (PD), a hypokinetic disorder, and Huntington's disease (HD), a hyperkinetic disorder, share the fact that in the motor pathways the dysfunction starts in the striatum. In PD the projection neurons are overactive due to decreased inhibitory regulation by lost dopamine afferents, while in HD the output from the striatum is insufficient due to loss of projection neurons. This study aimed to determine whether the introduction of a mild HD condition in the PD striatum can counter the hypokinetic condition. The experiment was carried out in the 6-OHDA rat model for PD in which amphetamine, 5 mg/kg, evokes an asymmetric rotation response toward the side of the 6-OHDA lesion (ipsilateral rotation). The response to amphetamine in this study was fractionated into multiple components and measured automatically. After baseline measurements, the subjects were divided into four groups. Group I was unilaterally sham-lesioned in medial, central, and lateral striatum. Group II was injected quinolinic acid (QA) 20 nM in medial, central, and lateral striatum. Group III was injected QA 60 nM in central striatum. Group IV was injected QA 120 nM in central striatum. The effects of QA were measured weekly. The sham lesions in Group I had no effects. In Group II, ipsilateral rotation was reduced and replaced by oral stereotypy, a competitive behavior. In Group III, ipsilateral rotation decreased, but to a lesser degree than in Group II. In Group IV, QA had no effects. Histological findings show a unilateral loss of tyrosine immunoreactive (TH) neurons in substantia nigra and of fibers in striatum in all subjects. In addition, in Group II the striatum was atrophied. These findings suggest that the shift in Group II from ipsilateral rotation to oral stereotypy after QA was due to reduced striatal output caused by a loss of projection neurons, a loss insufficient to induce HD symptoms, but sufficient to counter the PD condition.

Adrenergic Agents↗
PubMed2003

Behavioral and subthalamic effects of combining a fetal ventral mesencephalic transplant in striatum with an electrolytic lesion of the entopeduncular nucleus in the rat with a unilateral 6-OHDA lesion of substantia nigra.

Behavioral and electrophysiological methods were used to determine whether a transplant of dopamine-rich fetal tissue in striatum combined with an electrolytic lesion of the entopeduncular nucleus have additive effects in the unilaterally lesioned rat model for Parkinson's disease. The subjects were rats with the left substantia nigra lesioned with 6-hydroxydopamine (6-OHDA) and responding to systemic amphetamine with rotation toward the side of the lesion (ipsilateral rotation). The motor response to amphetamine was fractionated into six aspects, half reflecting the unilateral deafferentation in striatum and half representing those aspects of the response evoked in normal rats. After collection of baseline values, 25 rotators received a transplant of fetal ventral mesencephalic tissue in the left striatum and 20 received a transplant and, at the same time, an electrolytic lesion of the left entopeduncular nucleus. Testing for the motor response to amphetamine resumed after 4 weeks of recovery and continued at weekly intervals for 5 weeks. Upon completion of these tests, each rotator was implanted with multiple electrodes in the subthalamic nucleus. After recovery, multiunit responses to amphetamine and apomorphine were recorded from several electrodes in parallel during the motor response to the drugs. In rotators with transplant only, treatment with amphetamine evoked oral stereotypy and an attenuated ipsilateral rotation response. In rotators with combined transplant and entopeduncular lesion, ipsilateral rotation did not change or increased. Subthalamic responses to amphetamine and apomorphine were larger in rotators with combined transplant and entopeduncular lesion than in rotators with transplant alone. These findings indicate that the combination of transplant and pallidotomy in the 6-OHDA rat model for parkinsonism does not lead to additive benefits, an effect that may have been due to the nonselectivity of the electrolytic damage and/or of the lesion extending beyond the entopeduncular nucleus into the lateral hypothalamus.

Amphetamine↗
PubMed2001

Entopeduncular lesions facilitate and thalamic lesions depress spontaneous and drug-evoked motor behavior in the hemiparkinsonian rat.

Pallidotomy is a neurosurgical procedure designed to ameliorate the akinesia and bradykinesia associated with Parkinson's disease. In the present study, the effects of pallidal-like lesions on motor behavior in the hemiparkinsonian rat were compared to the effects of lesions in the ventrolateral thalamus, a target of entopeduncular projections feeding motor-related information to motor cortex. Six aspects of spontaneous and evoked behavior induced by amphetamine and apomorphine in the hemiparkinsonian rat with either bilateral electrolytic entopeduncular lesions or bilateral electrolytic ventrolateral thalamic lesions were measured for 60 min. Saline or amphetamine, 5 mg/kg, or apomorphine, 0.3 mg/kg, were administered IP 5 min before the tests. The results show that on all measures except time spent resting the hemiparkinsonian rats with the entopeduncular lesions were more active than the hemiparkinsonian rats with the thalamic lesions. The asymmetrical rotation responses to dopamine receptor stimulation evoked by amphetamine and apomorphine were influenced by the general effect on gross motor behavior, as shown by the response being very large in the entopeduncular group and very small in the thalamic group. These results are consistent with current thinking about the functional organization of the basal ganglia according to which damage of the entopeduncular nucleus reduces its inhibitory control of the thalamic motor regions, thereby promoting thalamic facilitation of motor cortex, and damage to the thalamic motor regions has the opposite effect. These effects of the lesions translate, respectively, into hyperactivity and hypoactivity without blocking the asymmetrical rotation response of the hemiparkinsonian rat.

Amphetamine↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed1999

Subthalamic responses to amphetamine and apomorphine in the behaving rat with a unilateral 6-OHDA lesion in the substantia nigra.

The activity of neurons in the subthalamic nucleus (STN) of the behaving rat, before and after a unilateral 6-OHDA lesion of the substantia nigra, was recorded with the extracellular technique to determine whether it was altered following systemic amphetamine, 5 mg/kg, apomorphine, 3 mg/kg, and apomorphine, 0.3 mg/kg, and whether in cases of altered activity, it was related to the drug-induced motor response expressed concurrently. Activity in the STN of intact rats increased dramatically after amphetamine, 5 mg/kg. This excitatory response had the same latency, similar magnitude, and the same duration as the motor response expressed in terms of locomotion and oral stereotypy. Motor and unit responses were also induced by amphetamine after the lesion with 6-hydroxydopamine (6-OHDA), but now the excitatory response was attenuated while the motor response was not. The effects of the 6-OHDA lesion were the same in all animals with loss of the nigra dopamine neurons, regardless of whether they were rotators or non-rotators. Activity in the STN of intact rats also increased after apomorphine, 3 mg/kg, and again, this increase was correlated with the increase in motor behavior, but both responses were of shorter duration than the responses to amphetamine. The increases in unit activity and motor behavior induced by apomorphine in the 6-OHDA-lesioned rats had the same magnitude but lasted longer than in the intact rats. Treatment with apomorphine, 0.3 mg/kg, of the intact rats produced small and very brief increases in the activity of the STN and in motor behavior. The same treatment given the 6-OHDA-lesioned rats produced responses of larger magnitude but no change in duration. These findings demonstrate a role for STN neurons in the mediation of the motor behaviors induced by stimulation of the dopamine receptor. The results also show that a unilateral lesion of the substantia nigra with 6-OHDA did not block these responses but altered them in a manner consistent with a dopaminergic deafferentation of the basal ganglia. The increased activity in the STN during the expression of dopamine-dependent motor behavior conflicts with the current model of basal ganglia function that assumes prejudicial effects of excessive STN activity on the expression of motor behavior. An explanation for this conflict suggests that it is more apparent than real.

Action Potentials↗
PubMed1999

Activation of neurotransplants in humans.

Clinical studies report symptomatic benefit in most fetal neurotransplantation treated Parkinson's disease patients. The underlying mechanism is incompletely explained. We investigated whether neural connections between host and transplanted tissue are established. Two Parkinson's disease patients with clinically excellent outcome after transplantation were studied with functional magnetic resonance imaging. A repetitive motor task that provided robust stimulation in the contralateral putamen in volunteers activated graft bearing regions of putamen in patients. In response to contralateral motor tasks, activation was recorded consistently in left putamen in patient 1 and in right putamen in patient 2. Functional magnetic resonance imaging suggests that neuronal rewiring contributes to the functioning of neurotransplants in vivo in humans.

Adult↗
PubMed1998

Globus pallidus lesions depress the excitatory responses to apomorphine but not amphetamine in the subthalamic nucleus of the behaving rat with a 6-OHDA nigra lesion.

The role of the dopaminergic innervation of the basal ganglia on the activity in the subthalamic nucleus (STN) evoked by amphetamine and apomorphine in the behaving rat was examined. The aim was to determine the relationship between that neural activity and the movements evoked by the drugs. Bilateral electrolytic lesions of the globus pallidus (GP), superimposed on the earlier unilateral lesion in substantia nigra (SN) with 6-hydroxydopamine (6-OHDA) affected differently the excitatory responses in the STN evoked by amphetamine and apomorphine and the motor responses to the drugs recorded concurrently. Before the GP lesions, the administration of amphetamine, 5 mg/kg, to the unilaterally deafferented rat induced increased activity in the STN and simultaneously increased movement in the animal. After the GP lesions, the excitatory response to amphetamine in the STN was not different from that seen before the GP lesions. The motor response was also unchanged. In contrast, the GP lesions altered the excitatory response to apomorphine, 3 mg/kg. Before these lesions, the administration of apomorphine to the 6-OHDA lesioned animal evoked a robust and long-lasting excitatory response in the STN and, concurrently, a long-lasting motor response. After the GP lesions, both responses to apomorphine were attenuated. These differential effects of the GP lesions on the unit and motor responses to the two drugs are viewed as representing the effects of the damage in the GP on the dopaminergic innervation contributing to the regulation of activity in the STN. In the 6-OHDA animal, the dopamine afferents innervating the basal ganglia had already been dramatically reduced by 6-OHDA. The GP lesions did not significantly add to the number of these afferents previously eliminated; therefore, the excitatory and motor responses to amphetamine were not changed by the GP lesions. But the GP damage served to eliminate the dopamine receptor in the GP and thus reduced the density of the dopamine receptor in the basal ganglia available for binding to apomorphine. Therefore, the excitatory and motor responses to apomorphine were attenuated after the GP lesions compared to the responses before these lesions.

Amphetamine↗
PubMed1998

Quantitative proton-decoupled 31P MRS and 1H MRS in the evaluation of Huntington's and Parkinson's diseases.

OBJECTIVE: To determine cerebral energy status in patients with Huntington's disease (HD) and Parkinson's disease (PD). METHODS: The study included 15 patients with DNA-proven, symptomatic HD and five patients with medically treated, idiopathic PD, all of whom were candidates for neurotransplant treatment, as well as 20 age-related normal subjects. Quantitative noninvasive, MRI-guided proton MRS was performed of single volumes in putamen of basal ganglia (BG), occipital gray matter, and posterior parietal white matter; in addition, quantitative phosphorus and proton-decoupled phosphorus MRS of superior biparietal white and gray matter was done. Outcome measures were quantitative metabolite ratios and millimolar concentrations of neuronal and glial markers, creatine (Cr) and adenosine triphosphate (ATP), and intracellular pH. RESULTS: In volume-corrected control BG (10.46 +/- 0.37 mM), [Cr] was 29% (p < 0.05) higher than in control gray matter (8.10 +/- 1.04 mM). In HD and PD, energy metabolism was not abnormal in the four cerebral locations measured by MRS. No increase in cerebral lactate or decrease in phosphocreatine and ATP was detected. Small, systematic abnormalities in N-acetylaspartate (NAA, decreased), Cr (decreased), choline-containing compounds (Cho, increased), and myoinositol (mI, increased) were demonstrable in all patient's individually and in summed spectra but were insufficient to make diagnosis possible in the individual patient. CONCLUSION: Previously described failure of global energy metabolism in HD was not confirmed. However, quantitative 1-hydrogen MRS and decoupled 31-phosphorus MRS are sensitive to +/-10% alterations in key cerebral metabolites, and may be of value in noninvasive monitoring of appropriate therapies.

Adenosine Triphosphate↗
PubMed1997

Microelectrode-guided posteroventral medial radiofrequency pallidotomy for Parkinson's disease.

The outcome of radiofrequency-guided posteroventral medial pallidotomy was investigated in 29 patients with recalcitrant Parkinson's disease. Extracellular recordings were obtained in the target region to differentiate the internal from the external globus pallidus, and distinct waveforms were recorded in each region. Stimulation of the target site further verified the lesion location. Of the 29 patients treated during the course of 1 year, none showed any adverse side effects (such as hemianopsia or hemiparesis) from the procedure. Significant and immediate improvement in motor involvement (dyskinesia, rigidity, dystonia, freezing, and tremor) was observed as measured by the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Patients experienced improvements in their condition as measured on a self-rating scale, and their ability to perform the activities of daily living was also significantly improved. Although the onset and duration of the effect of a single dose of levodopa did not change, the number of hours in an "off" state of dyskinesia per day was significantly decreased. These results provide further evidence, in a large group of patients, that posteroventral medial pallidotomy results in significant control of the motor symptoms of Parkinson's disease with a minimum of undesirable side effects.

Electrophysiology↗