ABSTRACT
The development of novel techniques for the in vivo, non-invasive visualization and identification of thalamic nuclei has represented a major challenge for human neuroimaging research in the last decades. Thalamic nuclei have important implications in various key aspects of brain physiology and many of them show selective alterations in various neurologic and psychiatric disorders. In addition, both surgical stimulation and ablation of specific thalamic nuclei have been proven to be useful for the treatment of different neuropsychiatric diseases. The present work aimed at describing a novel protocol for histologically guided delineation of thalamic nuclei based on short-tracks track-density imaging (stTDI), which is an advanced imaging technique exploiting high angular resolution diffusion tractography to obtain super-resolved white matter maps. We demonstrated that this approach can identify up to 13 distinct thalamic nuclei bilaterally with very high inter-subject (ICC: 0.996, 95% CI: 0.993-0.998) and inter-rater (ICC:0.981; 95% CI:0.963-0.989) reliability, and that both subject-based and group-level thalamic parcellation show a fair share of similarity to a recent standard-space histological thalamic atlas. Finally, we showed that stTDI-derived thalamic maps can be successfully employed to study structural and functional connectivity of the thalamus and may have potential implications both for basic and translational research, as well as for presurgical planning purposes.
Subject(s)
Thalamic Nuclei , White Matter , Diffusion Tensor Imaging/methods , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results , Thalamic Nuclei/diagnostic imaging , Thalamus/diagnostic imaging , Thalamus/physiologyABSTRACT
The aim of this study was to assess metabolic changes in the motor cortex in de novo Parkinson's disease (PD) patients before and after therapy with ropinirole. Twenty de novo drug-naïve PD patients and 15 healthy controls underwent conventional magnetic resonance imaging and proton magnetic resonance spectroscopy imaging ((1)H-MRSI). The resonance intensities of N-acetylaspartate (NAA) and choline (Cho) were normalized for the resonance intensities of creatine (Cr). At baseline, lower NAA/Cr and NAA/Cho ratios and higher Cho/Cr ratios were found in the motor cortex of PD patients compared with controls (p<0.001). Ten months after ropinirole treatment, PD patients showed a significant clinical improvement in the UPDRS motor sub-scores (p<0.001) and an increase of NAA/Cr and NAA/Cho ratios (p<0.006 and p=0.01, respectively). A highly significant correlation between NAA/Cr and NAA/Cho ratios and UPDRS motor sub-scores was observed (r=-0.981 and r=-0.983, respectively). We could argue that the ropinirole efficacy to improve the motor performances is the result of partial restoration of neuronal functions, due to the increase of NAA in motor cortex.
Subject(s)
Antiparkinson Agents/therapeutic use , Dopamine Agonists/therapeutic use , Indoles/therapeutic use , Motor Cortex/drug effects , Parkinson Disease/drug therapy , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Case-Control Studies , Choline/metabolism , Creatine/metabolism , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/metabolism , Parkinson Disease/metabolism , Proton Magnetic Resonance SpectroscopyABSTRACT
5-Arylidene-3-hydroxyalkyl-2-phenylimino-4-thiazolidinones (7,8) were synthesized and evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1beta. This in vitro model has proven to be a useful experimental model to reproduce the mechanisms involved in arthritic diseases. The cell viability, the amount of GAGs, the production of NO and PGE(2) and the inhibition of MMP-3 were measured. Several thiazolidinones 7 and 8 exhibited the ability to block the production or action of the degenerative factors induced by IL-1beta.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chondrocytes/drug effects , Imines/chemical synthesis , Models, Biological , Thiazolidines/chemical synthesis , Thiazolidines/pharmacology , Arthritis/drug therapy , Cell Survival/drug effects , Cells, Cultured , Chondrocytes/immunology , Drug Evaluation, Preclinical , Humans , Imines/pharmacology , Indomethacin/pharmacology , Interleukin-1beta/pharmacology , Reference StandardsABSTRACT
A number of 5-arylidene-2,4-thiazolidinediones containing a hydroxy or a carboxymethoxy group in their 5-benzylidene moiety have been synthesised and evaluated as in vitro aldose reductase (ALR2) inhibitors. Most of them exhibited strong inhibitory activity, with IC(50) values in the range between 0.20 and 0.70 microM. Molecular docking simulations into the ALR2 active site highlighted that the phenolic or carboxylic substituents of the 5-benzylidene moiety can favourably interact, in alternative poses, either with amino acid residues lining the lipophilic pocket of the enzyme, such as Leu300, or with the positively charged recognition region of the ALR2 active site.