Search PubMed⌕ Search

Biomedical subjects

K Seppi

Publications and source records attributed to K Seppi.

23 records · Page 2Linked to original sources

Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).

In the present experiment we studied the ability of embryonic striatal grafts to protect against striatal quinolinic acid (QA)-induced excitotoxicity in a previously established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats received under halothane inhalation anesthesia a 6-hydroxydopamine 6-OHDA injection into the left medial forebrain bundle. Four to 5 weeks later apomorphine-induced rotation behavior was tested. Rats were divided into two treatment groups receiving either embryonic striatal cell suspensions or sham injections. Apomorphine-induced rotation behavior was retested 2 and 4 weeks after the grafting procedure. Following the rotation test animals of the striatal and sham graft group received a stereotaxic injection of 150 nmol QA. Again rotation behavior was assessed 2 and 4 weeks after lesioning. Brains were then processed to dopamine reuptake ([(3)H]mazindol), dopamine D1 ([(3)H]SCH23390), and D2 ([(3)H]spiperone) receptor autoradiography. Gliosis was detected using [(3)H]PK11195, a marker for peripheral benzodiazepine binding sites. Behavioral and autoradiographic analysis failed to show striatal protection in 6-OHDA prelesioned animals receiving embryonic striatal grafts. These findings indicate that beneficial protective effects of striatal grafts implanted into host striatum prior to excitotoxic insults are abolished in the presence of severe dopaminergic denervation. Our present results are relevant to future applications of neural grafting in MSA-SND.

Animals↗

In vivo magnetic resonance imaging of embryonic neural grafts in a rat model of striatonigral degeneration (multiple system atrophy).

The effects of embryonic neural transplantation in experimental models of neurodegenerative disorders are commonly assessed by behavioral tests and postmortem neurochemical or anatomical analysis. The purpose of the present study was to evaluate embryonic neuronal grafts in a novel rat model of multiple system atrophy (MSA) with the help of in vivo magnetic resonance imaging (MRI) and to correlate imaging with histological parameters. Striatonigral double lesions were created in male Wistar rats by unilateral intrastriatal injection of 3-nitropropionic acid (3-NP). Seven weeks following lesion surgery animals were divided into four transplantation groups receiving either pure mesencephalic, pure striatal, mesencephalic-striatal cografts, or sham grafts. In vivo structural imaging was performed 21 weeks after transplantation using a whole body 1.5 Tesla MR scanner. The imaging protocol comprised T2-weighted TSE and T1-weighted TIR sequences. Immunohistochemistry using DARPP-32 as striatal marker and tyrosinhydroxylase as marker for nigral neurons was performed for correlation analysis of imaging and histological parameters. The sensitivity of graft detection by in vivo MRI was 100%. The graft tissue was clearly demarcated from the remaining striatal tissue in both T2- and T1-weighted sequences. Morphometrically, cross-sectional areas of the grafts and spared intact striatum as defined by immunohistochemistry correlated significantly with measurements obtained by in vivo MRI. In conclusion, we were able to evaluate in vivo both lesion-induced damage and graft size in a 3-NP rat model of MSA using a conventional whole body 1.5 Tesla MRI scanner. Additionally, we obtained an excellent correlation between MRI and histological measurements.

Animals↗

Depression in alpha-synucleinopathies: prevalence, pathophysiology and treatment.

Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are increasingly recognized as alpha-synucleinopathies, i.e. neurodegenerative disorders that share a common subcellular pathology characterized by alpha-synuclein abnormal aggregation. In the present review we focus on depression in alpha-synucleinopathies, discussing epidemiological, pathophysiological and treatment aspects of this frequently disabling clinical feature which may occur in PD, DLB and MSA alike.

Animals↗

[Dementia with Lewy bodies].

Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, parkinsonian syndrome, fluctuations of cognitive functions, alertness, and attention, visual hallucinations (usually detailed and well described), depression, REM sleep behavior disorder, adverse responses to standard neuroleptics doses, falls, syncopes, systematized delusions, and other modalities of hallucinations. Specificity of the clinical diagnostic criteria is high (95%), and sensitivity is considerably lower. Mean age at disease onset ranges between 60 and 68 years. The male gender prevails. Disease duration is 6 to 8 years. The differential diagnoses of DLB are dementia of the Alzheimer type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and rarely Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. Controlled pharmacological studies have so far not been published. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha receptor-blocking medications to improve neurogenic bladder dysfunction.

Aged↗

Seizures and death on a white river float trip. Report of water hemlock poisoning.

White river rafting is becoming a major summer recreational activity throughout the United States. Many people who are ill prepared physically or emotionally to survive will find themselves isolated and in extremely dangerous situations without access to medical help. In addition to the physical dangers of drowning, there are dangers that exist in the concept of "living off the land" and foraging for food. Cicuta douglasii is found in all of our western states, is extremely toxic and can easily be confused with wild parsnip or carrot. Physicians and poison control centers need to be aware of the common poisonous plants in their area and be prepared to treat cases of poisoning from these plants.

Adult↗