Characterization of fiber-optic light delivery and light-induced temperature changes in a rodent brain for precise optogenetic neuromodulation

Understanding light intensity and temperature increase is of considerable importance in designing or performing in vivo optogenetic experiments. Our study describes the optimal light power at target depth in the rodent brain that would maximize activation of light-gated ion channels while minimizing temperature increase. Monte Carlo (MC) simulations of light delivery were used to provide a guideline for suitable light power at a target depth. In addition, MC simulations with the Pennes bio-heat model using data obtained from measurements with a temperature-measuring cannula having 12.3 mV/°C of thermoelectric sensitivity enabled us to predict tissue heating of 0.116 °C/mW on average at target depth of 563 μm and specifically, a maximum mean plateau temperature increase of 0.25 °C/mW at 100 μm depth for 473 nm light. Our study will help to improve the design and performance of optogenetic experiments while avoiding potential over-and underillumination. © 2016 Optical Society of America.1

Radiofrequency Neurotomy of Cervical Medial Branches for Chronic Cervicobrachialgia

Chronic neck and arm pain or cervicobrachialgia commonly occurs with the degeneration of cervical spine. Authors investigated the usefulness of radiofrequency (RF) neurotomies of cervical medial branches in patients with cervicobrachialgia and analyzed the factors which can influence the treatment outcome. Demographic data, types of pain distribution, responses of double controlled blocks, electrical stimulation parameters, numbers and levels of neurotomies, and surgical outcomes were evaluated after mean follow-up of 12 months. Pain distribution pattern was not significantly correlated with the results of diagnostic blocks. Average stimulation intensity was 0.45 V, ranging from 0.3 to 0.69, to elicit pain response in cervical medial branches. The most common involvement of nerve branches was C4 (89%), followed by C5 (82%), C6 (75%), and C7 (43%). Among total of 28 patients, nineteen (68%) reported successful outcome according to outcome criteria after 6 months of follow-up (p=0.001), and eight (42%) of 19 patients reported complete relief (100%) of pain. Four patients showed recurrence of pain between 6 and 12 months. It was therefore concluded that cervical medial branch neurotomy is considered useful therapeutic modality for the management of cervicobrachialgia in selected patients, particularly in degenerative zygapophyseal disorders

Stem Cell Dynamics in an Experimental Model of Stroke

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke

Usefulness of Pain Distribution Pattern Assessment in Decision-Making for the Patients with Lumbar Zygapophyseal and Sacroiliac Joint Arthropathy

There are currently no initial guides for the diagnosis of somatic referred pain of lumbar zygapophyseal joint (LZJ) or sacroiliac joint (SIJ). We developed a classification system of LZJ and SIJ pain, the "pain distribution pattern template (PDPT)" depending on the pain distribution patterns from a pool of 200 patients whose spinal pain source was confirmed. We prospectively applied the PDPT to determine its contribution to clinical decision-making for 419 patients whose pain was presumed to arise from the LZJs (259 patients) or SIJs (160 patients). Forty-nine percent (128/259) of LZJ and 46% (74/160) of SIJ arthopathies diagnosed by PDPT were confirmed by nerve blocks. Diagnostic reliabilities were significantly higher in Type A and C patterns in LZJ and Type C in SIJ arthropathies, 64%, 80%, and 68.4%, respectively. For both LZJ and SIJ arthropathies, favorable outcome after radiofrequency (RF) neurotomies was similar to the rate of positive responses to diagnostic blocks in Type A to Type D, whereas the outcome was unpredictable in those with undetermined type (Type E). Considering the paucity of currently available diagnostic methods for LZJ and SIJ arthropathies, PDPT is useful in clinical decision-making as well as in predicting the treatment outcome

Clinical Relevance of Pain Patterns in Osteoporotic Vertebral Compression Fractures

Few studies have been conducted to explain the pain patterns resulting from osteoporotic vertebral compression fractures (OVCF). We analyzed pain patterns to elucidate the pain mechanism and to provide initial guide for the management of OVCFs. Sixty-four patients underwent percutaneous vertebroplasty (N=55) or kyphoplasty (N=9). Three pain patterns were formulized to classify pains due to OVCFs: midline paravertebral (Type A), diffuse paravertebral (Type B), and remote lumbosacral pains (Type C). The degree of compression was measured using scale of deformity index, kyphosis rate, and kyphosis angle. Numerical rating scores were serially measured to determine the postoperative outcomes. As vertebral body height (VBH) decreased, paravertebral pain became more enlarged and extended anteriorly (p<0.05). Type A and B patterns significantly showed the reverse relationship with deformity index (p<0.05), yet Type C pattern was not affected by deformity index. Postoperative pain severity was significantly improved (p<0.05), and patients with a limited pain distribution showed a more favorable outcome (p<0.05). The improvement was closely related with the restoration of VBH, but not with kyphosis rate or angle. Thus, pain pattern study is useful not only as a guide in decision making for the management of patients with OVCF, but also in predicting the treatment outcome

Upregulation of Glutamate Receptors in Rat Cerebral Cortex with Neuronal Migration Disorders

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immunohistochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs

Computational study on subdural cortical stimulation - the influence of the head geometry, anisotropic conductivity, and electrode configuration.

Subdural cortical stimulation (SuCS) is a method used to inject electrical current through electrodes beneath the dura mater, and is known to be useful in treating brain disorders. However, precisely how SuCS must be applied to yield the most effective results has rarely been investigated. For this purpose, we developed a three-dimensional computational model that represents an anatomically realistic brain model including an upper chest. With this computational model, we investigated the influence of stimulation amplitudes, electrode configurations (single or paddle-array), and white matter conductivities (isotropy or anisotropy). Further, the effects of stimulation were compared with two other computational models, including an anatomically realistic brain-only model and the simplified extruded slab model representing the precentral gyrus area. The results of voltage stimulation suggested that there was a synergistic effect with the paddle-array due to the use of multiple electrodes; however, a single electrode was more efficient with current stimulation. The conventional model (simplified extruded slab) far overestimated the effects of stimulation with both voltage and current by comparison to our proposed realistic upper body model. However, the realistic upper body and full brain-only models demonstrated similar stimulation effects. In our investigation of the influence of anisotropic conductivity, model with a fixed ratio (1∶10) anisotropic conductivity yielded deeper penetration depths and larger extents of stimulation than others. However, isotropic and anisotropic models with fixed ratios (1∶2, 1∶5) yielded similar stimulation effects. Lastly, whether the reference electrode was located on the right or left chest had no substantial effects on stimulation

The spatial distribution of current density of 1V using right and left reference electrode model.

<p>The results in the brain are the same with the reference electrode on the right (left) and the left (right). However, the distribution of current density is flipped horizontally only under the neck.</p

Geometric structure of the brain model.

<p>A realistic upper body model (a), realistic full brain-only model (b), and simplified extruded slab model (c).</p