Biomedical subjects

Jennifer Chlan-Fourney

Publications and source records attributed to Jennifer Chlan-Fourney.

5 recordsLinked to original sources

PubMed2003

Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P < 0.05) and dentate gyrus (P < 0.01) regions compared with vehicle control. In contrast, the atypical antipsychotic agents clozapine (10 mg/kg) and olanzapine (2.7 mg/kg) up-regulated BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P < 0.01). These findings demonstrate that the typical and atypical antipsychotic drugs differentially regulate BDNF mRNA expression in rat hippocampus.

Analysis of Variance↗

PubMed2003

Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients.

OBJECT: The current North American experience with minimally invasive vertebro- and kyphoplasty is largely limited to the treatment of benign osteoporotic compression fractures. The objective of this study was to assess the safety and efficacy of these procedures for painful vertebral body (VB) fractures in cancer patients. METHODS: The authors reviewed a consecutive group of cancer patients (21 with myeloma and 35 with other primary malignancies) undergoing vertebro- and kyphoplasty at their institution. Ninety-seven (65 vertebro- and 32 kyphoplasty) procedures were performed in 56 patients during 58 treatment sessions. The mean patient age was 62 years (+/- 13 years [standard deviation]) and the median duration of symptoms was 3.2 months. All patients suffered intractable spinal pain secondary to VB fractures. Patients noted marked or complete pain relief after 49 procedures (84%), and no change after five procedures (9%); early postoperative Visual Analog Scale (VAS) pain scores were unavailable in four patients (7%). No patient was worse after treatment. Reductions in VAS pain scores remained significant up to 1 year (p = 0.02, Wilcoxon signed-rank test). Analgesic consumption was reduced at 1 month (p = 0.03, Wilcoxon signed-rank test). Median follow-up length was 4.5 months (range 1 day-19.7 months). Asymptomatic cement leakage occurred during vertebroplasty at six (9.2%) of 65 levels; no cement extravasation was seen during kyphoplasty. There were no deaths or complications related to the procedures. The mean percentage of restored VB height by kyphoplasty was 42 +/- 21%. CONCLUSIONS: Percutaneous vertebro- and kyphoplasty provided significant pain relief in a high percentage of patients, and this appeared durable over time. The absence of cement leakage-related complications may reflect the use of 1) high-viscosity cement; 2) kyphoplasty in selected cases; and 3) relatively small volume injection. Precise indications for these techniques are evolving; however, they are safe and feasible in well-selected patients with refractory spinal pain due to myeloma bone disease or metastases.

Adult↗

PubMed2002

Brain-derived neurotrophic factor (BDNF) mRNA in rats with neonatal ibotenic acid lesions of the ventral hippocampus.

Increasing evidence suggests that schizophrenia is a neurodevelopmental disorder with a progressive course characterized by worsening of symptoms and morphological alterations within the brain. This suggests that a neurodegenerative component may exist in schizophrenia. The role of brain-derived neurotrophic factor (BDNF) in neurodevelopment, cell viability and synaptic plasticity led to the investigation of BDNF as a potential candidate molecule in the pathophysiology of schizophrenia. BDNF mRNA was examined by in situ hybridization in the prefrontal cortex and hippocampus of animals with neonatal ibotenic acid lesions of the ventral hippocampus, a putative neurodevelopmental animal model of schizophrenia. Results demonstrate that animals with neonatal ibotenic acid lesions of the ventral hippocampus have reduced basal levels of BDNF mRNA. It is possible that alterations in this trophic factor render animals more susceptible to neurodegenerative insults.

Animals↗

PubMed2002

Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration.

Apart from their differential propensities to block dopamine D2 and serotonin 5-HT2 receptors, the molecular mechanisms underlying the clinical efficacy of typical and atypical antipsychotics in schizophrenia are largely unknown. Given recent interest in the effects of antipsychotics on neurotrophic and other growth related factors, the effects of antipsychotics on brain-derived neurotrophic factor (BDNF), a neurotrophin crucial to the structural integrity of adult neurons, were investigated in male Wistar rats. Chronic (19 day) but not acute (45 min) antipsychotic administration significantly altered levels of hippocampal BDNF mRNA. In addition, whereas chronic treatment with the strong D2 receptor-blocker haloperidol significantly downregulated hippocampal BDNF mRNA, the selective 5-HT2 receptor-blocker ritanserin significantly upregulated CA1 hippocampal BDNF mRNA in comparison to controls. Since high doses of risperidone and clozapine produce potent inhibition of both 5-HT2 and D2 receptors, while lower doses produce significantly greater 5-HT2 vs. D2 receptor blockade, a dose-response study was employed to determine whether low doses of these atypical antipsychotics would also upregulate hippocampal BDNF mRNA in the absence of significant D2 receptor blockade. Whereas chronic haloperidol and high-dose risperidone significantly downregulated hippocampal BDNF mRNA, intermediate and lower doses of risperidone and clozapine were, unlike ritanserin, without effect when compared to controls. Thus, although the long-term downregulation of hippocampal BDNF mRNA may underlie the different clinical profiles of certain antipsychotics, this effect seems to be associated with antipsychotic doses that not only cause significant D2 receptor inhibition, but are usually associated with side effects rather than therapeutic efficacies.

Animals↗

PubMed2002

Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus.

Quetiapine is a new atypical antipsychotic drug widely used in the treatment of schizophrenia and other psychotic disorders. This study examined the influence of quetiapine on the decrease of brain-derived neurotrophic factor (BDNF) expression, induced by chronic immobilization stress, in the hippocampus of the rat. Pretreatment with 10 mg/kg of quetiapine markedly attenuated the stress-induced decrease in levels of BDNF protein, as determined by Western blot analyses, and the reduction of BDNF immunoreactivity, in hippocampal pyramidal and dentate granular neurons. These results suggest that the chronic administration of quetiapine could be neuroprotective to hippocampal neurons in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.

Animals↗