Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate

Brotchie, Jonathan M.; Mitchell, Ian; Sambrook, M.A.; Crossman, Alan R.

doi:10.1002/mds.870060208

Cited by 202 publications

(91 citation statements)

References 10 publications

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“…Recent studies have provided better understanding of the functional organization of the basal ganglia circuitry and the pathophysiological mechanisms of PD. [1,3,4,6,7] In summary, the loss of dopaminergic nigrostriatal neurons is thought to result in a dysfunction of the two parallel segregated striatopallidal pathways. In the indirect pathway, increased activity of the inhibitory striato-GPe projection reduces the firing of inhibitory GPe neurons projecting to the subthalamic nucleus (STN).…”

Section: Discussionmentioning

confidence: 99%

Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis

Krauss¹,

Desaloms²,

Lai³

et al. 1997

FOC

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The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid-shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/− 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/− 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia “off” scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.

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Section: Discussionmentioning

confidence: 99%

Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis

Krauss¹,

Desaloms²,

Lai³

et al. 1997

FOC

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“…Local administration of non-NMDA antagonists into basal ganglia output nuclei produced marked anti-akinetic effects in animals with parkinsonian symptoms (Brotchie et al 1991(Brotchie et al , 1992Graham et al 1990;Klockgether et al 1991). It was suggested that these effects are brought about by a blockade of non-NMDA receptors in basal ganglia output nuclei which are overactive in this condition.…”

Section: Discussionmentioning

confidence: 99%

The non-NMDA glutamate receptor antagonist GYKI 52466 counteracts locomotor stimulation and anticataleptic activity induced by the NMDA antagonist dizocilpine

Hauber

Andersen

1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Summary.The effects of the non-NMDA glutamate receptor antagonist GYKI 52466 (2.4 and 4.8 mg/kg, i.p.) on spontaneous locomotor activity and haloperidol-induced catalepsy (0.5 mg/kg, i.p.) were assessed in naive rats and in rats pretreated with the NMDA antagonist dizocilpine (0.08 mg/kg, i.p.). GYKI 52466 given alone did not alter locomotor activity and haloperidol-induced catalepsy, but significantly antagonized the dizocilpineinduced locomotor stimulation and counteracted the anti-cataleptic effects of dizocilpine on haloperidol-induced catalepsy. Thus blockade of non-NMDA glutamate receptors antagonized the behavioural stimulant effects of a NMDA receptor blockade.

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“…These results are particularly important because the non-competitive NMDA-antagonist MK-801, although effective in rodent models of Parkinson's disease, was not active in the MPTP-treated common marmoset when administered alone (Close et al, 1990) and did not exert additive effects to L-Dopa in another primate species (Crossman et al, 1989) in the same model. In contrast, CPP (Crossman, personal communication) and the glutamate antagonist kynurenate reverse akinesia in the MPTP-treated common marmoset following focal injection into the medial pallidum (Brotchie et al, 1991). Lesion of the subthalamic nucleus by focal injection of the neurotoxin ibotenic acid also ameliorates parkinsonian symptomatology in MPTP-treated green monkeys (Bergman et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease

Löschmann¹,

Lange

Kunow³

et al. 1991

J Neural Transm Gen Sect

135

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Summary. Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPAantagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.

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Alleviation of parkinsonism by antagonism of excitatory amino acid transmission in the medial segment of the globus pallidus in rat and primate

Cited by 202 publications

References 10 publications

Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis

Microelectrode-guided posteroventral pallidotomy for treatment of Parkinson's disease: postoperative magnetic resonance imaging analysis

The non-NMDA glutamate receptor antagonist GYKI 52466 counteracts locomotor stimulation and anticataleptic activity induced by the NMDA antagonist dizocilpine

Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-Dopa in models of Parkinson's disease

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