Exploring diazepam’s effect on hemodynamic responses of mouse brain tissue by optical spectroscopic imaging

Abstract

Abstract:In this study, a simple duel-optical spectroscopic imaging apparatus capable of simultaneously determining relative changes in brain oxy-and deoxy-hemoglobin concentrations was used following administration of the anxiolytic compound diazepam in mice with strong dominant (Dom) and submissive (Sub) behavioral traits. Three month old mice (n = 30) were anesthetized and after 10 min of baseline imaging, diazepam (1.5 mg/kg) was administered and measurements were taken for 80 min. The mouse head was illuminated by white light based LED's and diffused reflected light passing through different channels, consisting of a bandpass filter and a CCD camera, respectively, was collected and analyzed to measure the hemodynamic response. This work's major findings are threefold: first, Dom and Sub animals showed statistically significant differences in hemodynamic response to diazepam administration. Secondly, diazepam was found to more strongly affect the Sub group. Thirdly, different time-series profiles were observed post-injection, which can serve as a possible marker for the groups' differentiation. To the best of our knowledge, this is the first report on the effects of an anxiolytic drug on brain hemodynamic responses in mice using diffused light optical imaging. References and links1. R. C. Kessler, P. Berglund, O. Demler, R. Jin, K. R. Merikangas, and E. E. Walters, "Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication," Arch. Gen. Psychiatry 62(6), 593-602 (2005 894-902 (2008). 4. M. T. Berlim, M. P. Fleck, and G. Turecki, "Current trends in the assessment and somatic treatment of resistant/refractory major depression: an overview," Ann. Med. 40(2), 149-159 (2008). 5. C. J. Harmer, G. M. Goodwin, and P. J. Cowen, "Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action," Br. Ntziachristos, and B. Chance, "Non-invasive and quantitative near-infrared haemoglobin spectrometry in the piglet brain during hypoxic stress, using a frequency-domain multidistance instrument," Phys. Med. Biol. 46(1), 41-62 (2001).

Voxel based morphometry in optical coherence tomography: validation and core findings

“…The registration method described by Chen et al 13 begins by using the fovea as a global landmark to affinely align two OCT images. Each A-scan is subsequently rescaled to align the inner limiting membrane (ILM) and Bruch’s membrane (BM), and finally, 1D radial basis functions are used to register the retinal layers.…”

“…The average of these centered scans was then used as the initial reference and the scans are registered to it using the deformable registration approach. 13 These registered scans were then averaged to create a new atlas. This process – of registering to the atlas and then updating to a new average–is iterated through until changes in the average image fall below a threshold.…”

“…The key component in any VBM, including RAVENS, is a deformable registration method that can be used to build unbiased normalized atlases and map subjects into those atlases. The recent work of Chen et al 12,13 presented an intensity based deformable registration based approach for OCT data with a preliminary demonstration of the potential application of the approach. A brief review of Chen et al 12,13 is included in Section 2.…”

Drug interactions with dementia‐related pathophysiological pathways worsen or prevent dementia

“…In addition, the chronic administration of BZDs in mice decreases the BDNF levels and inhibits hippocampal plasticity (Zhao et al, 2012). BZD could also induce neuronal death through a hypoxia mechanism caused by changes in the brain haemodynamic response (Abookasis, Shochat, Nesher, & Pinhasov, 2014).…”