Although extrapyramidal features in normal pressure hydrocephalus(NPH) are not uncommon, presentations with Parkinson's syndrome as the predominant feature are rare, especially in children, and may give rise to diagnostic difficulties. We presents a case of NPH manifested by Parkinson's syndrome cured by shunt revision. The patient had the long history of Parkinson's syndrome not responded by drug therapy. Failure of patients with parkinsonism to respond to therapy, should alert one to the possibility of shunt malfunction and NPH.
Child ; Drug Therapy ; Humans ; Parkinsonian Disorders*

OBJECTIVES: For Parkinsonian patients who had not reacted favorably on drug therapy are good candidate for ventroposterolateral pallidotomy, although not curative. We studied these patients after unilateral pallidotomy, to confirm the effectiveness and safety of this procedure. METHODS: We evaluated the 17 patients with idiopathic Parkinson's diesease who had undergone unilateral posteroventral pallidotomy. All patients responded to levodopa initially. Mean age was 55 years(38-75years), and mean duration of disease was 9.8 years(3-20years). Pre-and postoperative evaluation at 3 month intervals included Unified Parkinson's Disease Rating scale(UPDRS) scoring, Hoehn and Yahr(H and Y) staging, and neuropsychological examinations. RESULTS: Pallidotomy significantly improved parkinsonian symptom(tremor, rigidity, bradykinesia, dyskinesia, sensory symptom). Nine of 10 patients who showed dyskinesia preoperatively significant improvement. The mean dose of levodopa in 9 patients was lowered. The mean H and Y score and UPDRS score were improved in on and/or off time in 15 patients. Among patients who were not improved, one patient worsened, and the others showed no change. The mean overall UPDRS off score changed from 76 preoperatively to 44(33%) at 6 months and from 70 to 52(25%) at 1 year. Transient surgical morbidity was showen in four patients and included dysarthria, hypotonia and confusion. CONCLUSION: We conclude that pallidotomy is safe and effective in patients who have levodopa-reponsive parkinsonism with severe symptom fluctuation. Unilateral pallidotomy also considered helpful to ipsilateral symptom. Unilateral pallidotomy can improve all of parkinsonian's symptom and allow to reduce the levodopa medication. Most of patients show satisfactory results.
Drug Therapy ; Dysarthria ; Dyskinesias ; Humans ; Hypokinesia ; Levodopa ; Muscle Hypotonia ; Pallidotomy* ; Parkinson Disease ; Parkinsonian Disorders

Two hundred and four patients with Parkinson's disease initially treated wth a combination of levodopa and carbidopa ( Sinement 25-250 ) and / or anticholinergic drugs. All patients responded initially to drug. Sixteen patients(7.8%) had 20 acute central nervous system side effects: 8, dyskinesia: 6, visual hallucination:5, psychosis: and 1, akathisia. The response to treatment usually was stable for the first one and a half to four years of drug therapy. Subsequently, over 50 percent of patients had therapeutic failure among 82 patients with long term drug therapy, fourteen(l7.0%) had 18 side effects: 8, on-off phenomenon: 4. Morning dystonia: 3, dyskinesia:and 3, simultaneous dyskinesia with parkinsonism. None had diphasic dyskinesia or myoclonus. The prognosis of the demented parkinsonian was relatively poor. Two patients died due to pneumonia and ovarian carcinoma.
Carbidopa ; Central Nervous System ; Drug Therapy ; Dyskinesias ; Dystonia ; Humans ; Levodopa ; Myoclonus ; Parkinson Disease* ; Parkinsonian Disorders ; Pneumonia ; Prognosis ; Psychomotor Agitation ; Psychotic Disorders

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

OBJECTIVETo observe the protective effect of baicalin on mouse with Parkinson's disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

METHODSThe mouse model of Parkinson's disease was established by intraperitoneal injection of MPTP at the daily dose of 30 mg/kg for 3 days to the aged (ten months old) C57BL mouse. And to the model mice in the tested group, baicalin (100 mg/kg) was given via gastric perfusion per day for 15 days. The motor function of limbs in mice was tested through hanging and swimming tests; the dopamine content of striatum was measured by HPLC; and the contents of malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-Px) in the brain tissue were measured by spectrophotography. Besides, the freezing section of mouse brain was made through immunohistochemical stain with tyrosine hydroxylase (TH) to determine the condition of dopaminergic neuron damage in mesencephalon.

RESULTS(1) The decreased score in the hanging test and swimming test, the reduced DA contents of striatum and lessening of TH positive neurons in substantial nigra illustrated the model of Parkinson's disease was successfully established. (2) Medication of baicalin could prevent the loss of TH positive neurons in substantial nigra and the decrease of dopamine content of striatum in Parkinson mouse, and significantly raise the content of GSH in the brain, but MPTP induced motor dysfunction in model mouse was not significantly improved by a short-time medication.

CONCLUSIONThe preventive medication of baicalin shows a protective effect on C57 BL mouse with Parkinson's disease induced by MPTP.

Animals ; Antioxidants ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Flavonoids ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Parkinsonian Disorders ; drug therapy ; Phytotherapy ; Random Allocation

BACKGROUNDHuman amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons. Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.

METHODSThe Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group. Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.

RESULTSThe rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P < 0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P < 0.01). Tyrosine hydroxylase (TH) positive cells in the substantia nigra of the HAEC group and the NS group were decreased compared to the untreated group (P < 0.01). Dopamine and DOPAC levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.05). Homovanillic acid (HVA) levels in the striatum of the HAECs group increased significantly compared to the NS group (P < 0.01). In addition dopamine, DOPAC, and HVA levels in the striatum and dopamine levels in the cerebrospinal fluid of the HAECs group and the NS group were decreased compared to the untreated group (P < 0.05).

CONCLUSIONSHuman amniotic epithelial cells could be used to ameliorate the rotational asymmetry induced by apomorphine of the PD models. This could have been due to the increased content of dopamine and its metabolic products, DOPAC and HVA, in the striatum in the PD models.

Amnion ; cytology ; Animals ; Apomorphine ; pharmacology ; Chromatography, High Pressure Liquid ; Epithelial Cells ; cytology ; drug effects ; transplantation ; Female ; Homovanillic Acid ; metabolism ; Humans ; Immunohistochemistry ; Oxidopamine ; toxicity ; Parkinsonian Disorders ; chemically induced ; metabolism ; therapy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protective effects of triptolide (Tri) on the lipopolysaccharide (LPS)-mediated degeneration of dopaminergic neurons in substantia nigra.

METHODSForty SD rats were randomly divided into four groups: the sham group, the LPS model group, the Tri group and the normal saline group, 10 in each group. Fourteen days later, the apomorphine-induced rotational behavior, the content of dopamine (DA) and its metabolites in the striatum of the injured side, the number of tyrosine-hydroxylase (TH) positive neurons and activation of microglia in rats were observed.

RESULTSInjection of LPS in substantia nigra could induce cerebral simulated immunoinflammatory reaction, leading to degeneration of dopaminergic neuron and induce ipsilateral directed rotational behavior of rats, which could be improved by Tri. Moreover, Tri could raise the lowered content of DA and its metabolites as well as the TH positive neurons in striatum, and suppress the activation of microglia significantly (P<0.01).

CONCLUSIONTri could protect the dopaminergic neurons from degeneration due to the inflammation mediated by LPS through inhibiting the activation of microglia.

Animals ; Diterpenes ; pharmacology ; therapeutic use ; Dopamine ; metabolism ; Epoxy Compounds ; pharmacology ; therapeutic use ; Female ; Inflammation Mediators ; pharmacology ; therapeutic use ; Lipopolysaccharides ; Neurons ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Parkinsonian Disorders ; chemically induced ; drug therapy ; pathology ; Phenanthrenes ; pharmacology ; therapeutic use ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; pathology

OBJECTIVENeuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.

METHODSThe rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.

RESULTSIntranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.

CONCLUSIONThese data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.

1-Methyl-4-phenylpyridinium ; antagonists & inhibitors ; toxicity ; Animals ; Biomarkers ; metabolism ; CD11b Antigen ; analysis ; metabolism ; Cell Count ; Cell Survival ; drug effects ; physiology ; Disability Evaluation ; Diterpenes ; pharmacology ; therapeutic use ; Dopamine ; metabolism ; Encephalitis ; drug therapy ; immunology ; prevention & control ; Epoxy Compounds ; pharmacology ; therapeutic use ; Gliosis ; drug therapy ; immunology ; prevention & control ; Herbicides ; antagonists & inhibitors ; toxicity ; Immunosuppression ; methods ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Microglia ; drug effects ; immunology ; Neurons ; drug effects ; immunology ; pathology ; Parkinsonian Disorders ; drug therapy ; immunology ; physiopathology ; Phenanthrenes ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; immunology ; physiopathology ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; analysis ; metabolism

The traditionally used oriental herbal medicine Moutan Cortex Radicis [MCR; Paeonia Suffruticosa Andrews (Paeoniaceae)] exerts anti-inflammatory, anti-spasmodic, and analgesic effects. In the present study, we investigated the therapeutic effects of differently fractioned MCR extracts in a 6-hydroxydopamine (OHDA)-induced Parkinson's disease model and neuro-blastoma B65 cells. Ethanol-extracted MCR was fractionated by n-hexane, butanol, and distilled water. Adult Sprague-Dawley rats were treated first with 20 μg of 6-OHDA, followed by three MCR extract fractions (100 or 200 mg·kg) for 14 consecutive days. In the behavioral rotation experiment, the MCR extract-treated groups showed significantly decreased number of net turns compared with the 6-OHDA control group. The three fractions also significantly inhibited the reduction in tyrosine hydroxylase-positive cells in the substantia nigra pars compacta following 6-OHDA neurotoxicity. Western blotting analysis revealed significantly reduced tyrosine hydroxylase expression in the substantia nigra pars compacta in the 6-OHDA-treated group, which was significantly inhibited by the n-hexane or distilled water fractions of MCR. B65 cells were exposed to the extract fractions for 24 h prior to addition of 6-OHDA for 30 min; treatment with n-hexane or distilled water fractions of MCR reduced apoptotic cell death induced by 6-OHDA neurotoxicity and inhibited nitric oxide production and neuronal nitric oxide synthase expression. These results showed that n-hexane- and distilled water-fractioned MCR extracts inhibited 6-OHDA-induced neurotoxicity by suppressing nitric oxide production and neuronal nitric oxide synthase activity, suggesting that MCR extracts could serve as a novel candidate treatment for the patients with Parkinson's disease.
Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Antiparkinson Agents ; pharmacology ; therapeutic use ; Cell Death ; drug effects ; Cell Line ; Disease Models, Animal ; Drugs, Chinese Herbal ; chemistry ; Neurons ; pathology ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type I ; biosynthesis ; Oxidopamine ; toxicity ; Paeonia ; chemistry ; Parkinsonian Disorders ; chemically induced ; drug therapy ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Plants, Medicinal ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; enzymology ; Tyrosine 3-Monooxygenase ; genetics ; metabolism