Symmetry differences of structural connectivity in multiple sclerosis and healthy state.

Focal and diffuse cerebral damages occur in Multiple Sclerosis (MS) that promotes profound shifts in local and global structural connectivity parameters, mainly derived from diffusion tensor imaging. Most of the reconstruction analyses have applied conventional tracking algorithms largely based on the controversial streamline count. For a more credible explanation of the diffusion MRI signal, we used convex optimization modeling for the microstructure-informed tractography2 (COMMIT2) framework. All multi-shell diffusion data from 40 healthy controls (HCs) and 40 relapsing-remitting MS (RRMS) patients were transformed into COMMIT2-weighted matrices based on the Schefer-200 parcels atlas (7 networks) and 14 bilateral subcortical regions. The success of the classification process between MS and healthy state was efficiently predicted by the left DMN-related structures and visual network-associated pathways. Additionally, the lesion volume and age of onset were remarkably correlated with the components of the left DMN. Using complementary approaches such as global metrics revealed differences in WM microstructural integrity between MS and HCs (efficiency, strength). Our findings demonstrated that the cutting-edge diffusion MRI biomarkers could hold the potential for interpreting brain abnormalities in a more distinctive way.

Long-term bumetanide administration altered behavioral pattern in mosaic Down's Syndrome: A case report.

The behavioral phenotypes emerge from cognitive architecture comprising attention, executive functions, and primary communication skills that all have shown remarkable deficits in Down's Syndrome (DS). These states arise from the proper functional interactions of the contributing neurotransmission and neuromodulation systems and other coding platforms. Gamma-aminobutyric acid (GABA) is an integral part of the neural interaction and regulation networks that its reverse action leads to broad detrimental consequences. This inhibitory substance needs an appropriate balance of co-transporters that largely shape the ionic milieu. Bumetanide, a specific NKCC1 inhibitor used for an eighteen-month interval, showed promising effects in restoring some behavior deficits in a fourteen-year-old boy diagnosed with genetically confirmed mosaic Down's Syndrome.

The Volumetric Changes of the Pineal Gland with Age: An Atlas-based Structural Analysis.

INTRODUCTION: There are numerous reports on the facilitatory role of the pineal gland (PG) in brain function, and the size this structure is suggested to be associated with its proper functionality. Previous works which studied the volume of the PG were mostly based on manual delineation of this region. In a recent work, we developed an MRI atlas for the PG in the standard space, with one of its applications being in volumetric studies. METHODS: In this study, using structural MRI data from 295 healthy participants in the age range of 19 to 76 years old, and using robust volumetric methods which included the above-mentioned atlas, we estimated the association of ageing with the changes of the PG volume, along with the volume of 48 other brain structures. RESULTS: We observed a linear decline (r= -0.42) over this age range for the PG volume, which showed similarity to the ageing profile of most of the other brain structures. Also, the PG volume showed significant associations with the scores of 9 cognitive tests. CONCLUSION: This study is the first work with an automated approach to estimate the PG volume, and could be a help to better understand the functionality of the PG in older ages.

PHBV nanofibers promotes insulin-producing cells differentiation of human induced pluripotent stem cells.

Tissue-engineering associated techniques have long been employed to improve the various elements of the therapeutic approaches toward the more efficient ones in diabetic states. The resultant constructs comprise of the polymeric scaffolds with proper degradation rates that produce bodily compatible components, and the pluripotent cells that are highly capable of generating islet-like cells. In this study, Poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers were fabricated by the Electrospinning. After validation of its 3-D structure, fibers size and non-toxicity, insulin-producing cells (IPC) differentiation potential of the induced pluripotent stem cells (iPSCs) were evaluated during growing on the PHBV nanofibers in comparison with tissue culture polystyrene (TCPS). SEM analyses confirmed the 3-D and nanofibrous structure of the fabricated scaffold. The survival rate of the iPSCs cultured on the PHBV nanofibers was increased significantly compared to the cells cultured on the TCPS, which is an evidence for the non-toxicity of the nanofibers. Insulin and C-peptide secretion levels significantly increased in the differentiated iPSCs on PHBV nanofibers compared to those cells cultured on TCPS. Moreover, levels of the gene transcription and translation results revealed that insulin, Glut-2, and Pdx-1 genes and insulin protein, in IPC-differentiated iPSCs grown on PHBV nanofibers are significantly higher than those cells grown on TCPS. Taken together, these results go beyond previous reports, showing thatiPSCs-PHBV as a promising cell-copolymer construct, could potentially be applied in the pancreatic tissue engineering applications to diabetic patient treatment.

Preliminary study of analgesic effect of bumetanide on neuropathic pain in patients with spinal cord injury.

BACKGROUND/OBJECTIVE: The current study evaluated the analgesic effects of bumetanide as an adjunctive treatment in managing neuropathic pain following spinal cord injury. The peripheral expression level of Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2) genes in polymorphonuclear lymphocytes (PMLs) assessed as a possible biomarker indicating central underlying mechanisms. METHODS: This open-label, single-arm, pilot trial of bumetanide (2 mg/day) is an add-on treatment conducted in 14 SCI patients for 19 weeks. The whole duration consisted of three phases: pre-treatment (1 month), titration (3 weeks), and active treatment (4 months). Ultimately, nine patients completed the study. The primary outcome variables were the endpoint pain score measured by the numeric rating scale (NRS), and the short-form McGill Pain Questionnaire. Secondary endpoints included the Short-Form Health Survey that measures the quality of life. Blood samples were collected and used for determining the expression of NKCC1 and KCC2 genes in transcription and translation levels. RESULTS: Bumetanide treatment significantly reduced average pain intensity according to the NRS and the short form of the McGill Pain Questionnaire scores. The baseline expression of KCC2 protein was low between groups and increased significantly following treatment (P < 0.05). Through the current study, pain improvement accompanied by the more significant mean change from the baseline for the overall quality of life. CONCLUSION: These data might be a piece of preliminary evidence for the analgesic effect of bumetanide on neuropathic pain and could support the potential role of the upregulation of KCC2 protein and involvement of GABAergic disinhibition in producing neuropathic pain.

Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy.

Antiepileptic drugs (AEDs) have repeatedly shown inconsistent and almost contradictory effects on the neurocognitive system, from substantial impairments in processing speed to the noticeable improvement in working memory and executive functioning. Previous studies have provided a novel insight into the cognitive improvement by bumetanide as a potential antiepileptic drug. Through the current investigation, we evaluated the longitudinal effects of bumetanide, an NKCC1 co-transporter antagonist, on the brain microstructural organization as a probable underlying component for cognitive performance. Microstructure assessment was completed using SPM for the whole brain assay and Freesurfer/TRACULA for the automatic probabilistic tractography analysis. Primary cognitive operations including selective attention and processing speed, working memory capacity and spatial memory were evaluated in 12 patients with a confirmed diagnosis of refractory epilepsy. Participants treated with bumetanide (2 mg/ day) in two divided doses as an adjuvant therapy to their regular AEDs for 6 months, which followed by the re-assessment of their cognitive functions and microstructural organizations. Seizure frequency reduced in eight patients which accompanied by white matter reconstruction; fractional anisotropy (FA) increased in the cingulum-cingulate gyrus (CCG), anterior thalamic radiation (ATR), and temporal part of the superior longitudinal fasciculus (SLFt) in correlation with the clinical response. The voxel-based analysis in responder patients revealed increased FA in the left hippocampus, right cerebellum, and right medial temporal lobe, while mean diffusivity (MD) values reduced in the right occipital lobe and cerebellum. Microstructural changes in SLFt and ATR accompanied by a reduction in the error rate in the spatial memory test. These primary results have provided preliminary evidence for the effect of bumetanide on cognitive functioning through microstructural changes in patients with drug-resistant epilepsy.