Deep Brain Stimulation in Treatment-Resistant Depression in Mice: Comparison With the CRF1 Antagonist, SSR125543.

Deep brain stimulation in treatment-resistant depression in mice: comparison with the CRF1 antagonist, SSR125543.

Filed under: Drug and Alcohol Rehabilitation

Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jan 10; 40: 213-20
Dournes C, Beeské S, Belzung C, Griebel G

Deep brain stimulation (DBS) has been demonstrated to represent a targeted therapeutic alternative for treatment-resistant depression. In this study, we used the unpredictable chronic mild stress (UCMS) test to validate high-frequency electrical stimulation of the cingulate cortex (CC) as a possible treatment to improve behavioral symptoms associated with a depressive-like state in treatment-resistant mice. The effects of DBS were compared with those of the CRF(1) antagonist, SSR125543. Mice were subjected to UCMS, which consisted of the sequential and unpredictable application of mild stressors for a total of 8 weeks. From week 4 until the end of week 6, mice received either a saline injection or were treated with the antidepressant, fluoxetine (10 mg/kg, i.p.). At the end of week 6, fluoxetine-treated mice were subdivided into two populations, that is one responding to fluoxetine, and one not responding, based on their fur coat state, an index of depressive-like state in this test. Non-responders were subsequently subjected to bilateral DBS (at 80 or 120 Hz, 1-h/day) or were treated with SSR125543 (20 mg/kg, i.p.) for two weeks. Stimulation of the CC at 120 Hz in treatment-resistant mice resulted in a normalization of motivated-like responses, anxiety-related behaviors, hyperactivity and aggressiveness. SSR125543 improved motivated-like and aggressive behaviors. These findings demonstrate that bilateral DBS of the CC and, to a lesser extent, pharmacological blockade of the CRF(1) receptor in treatment-resistant mice can attenuate several aspects of depressive-like behaviors, suggesting further that these approaches may represent valid alternatives for the treatment of drug-resistant depressed and/or anxious patients.
HubMed – drug


A framework for personalization of coronary flow computations during rest and hyperemia.

Filed under: Drug and Alcohol Rehabilitation

Conf Proc IEEE Eng Med Biol Soc. 2012 Aug; 2012: 6665-8
Sharma P, Itu L, Zheng X, Kamen A, Bernhardt D, Suciu C, Comaniciu D

We introduce a Computational Fluid Dynamics (CFD) based method for performing patient-specific coronary hemodynamic computations under two conditions: at rest and during drug-induced hyperemia. The proposed method is based on a novel estimation procedure for determining the boundary conditions from non-invasively acquired patient data at rest. A multi-variable feedback control framework ensures that the computed mean arterial pressure and the flow distribution matches the estimated values for an individual patient during the rest state. The boundary conditions at hyperemia are derived from the respective rest-state values via a transfer function that models the vasodilation phenomenon. Simulations are performed on a coronary tree where a 65% diameter stenosis is introduced in the left anterior descending (LAD) artery, with the boundary conditions estimated using the proposed method. The results demonstrate that the estimation of the hyperemic resistances is crucial in order to obtain accurate values for pressure and flow rates. Results from an exhaustive sensitivity analysis have been presented for analyzing the variability of trans-stenotic pressure drop and Fractional Flow Reserve (FFR) values with respect to various measurements and assumptions.
HubMed – drug


Enhanced directionality of bio-hybrid mobile microrobots using non-spherical body geometries.

Filed under: Drug and Alcohol Rehabilitation

Conf Proc IEEE Eng Med Biol Soc. 2012 Aug; 2012: 6580-2
Sahari A, Headen D, Behkam B

Mobile microrobots are envisioned to be employed for several applications including drug delivery, diagnostic imaging and environmental monitoring. In the bio-hybrid microrobot that is presented here, microparticles are used as the body of the microrobot and bacterial cells are utilized to realize on-board actuation. In this work, the importance of body shape on the dynamics of bacteria-propelled swimming microrobots (BacteriaBots) is investigated. We have shown that, with the use of non-spherical microparticles, average directionality of the BacteriaBots is enhanced compared with the spherical BacteriaBots.
HubMed – drug


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