Schizophrenia And Red Light: Fmri Evidence For A Novel Biobehavioral Marker

Previous research has demonstrated the ability of diffuse red light to suppress activity in the magnocellular (M) visual pathway. An earlier psychophysical study found that a subset of nonpsychotic relatives of persons with schizophrenia showed the opposite effect when compared to healthy adults (Bedwell et al., 2003), suggesting a novel biobehavioral marker for the disorder. The present study attempted to replicate and explore the mechanism for this effect using fMRI. Results provide physiological evidence that the M pathway response to red light is in the opposite direction than expected in a subset of nonpsychotic relatives of persons with schizophrenia. Copyright © 2006 Informa Healthcare

Improved cardiac manganese-enhanced MRI (MEMRI) with T1 mapping in rodent

Manganese ion (Mn 2+ ) is an intracellular contrast agent that enters viable myocardial cells via voltage gated calcium channels. Along with its T 1 shortening effect and relatively long half-life in cells, it becomes a very useful molecular contrast agent to study calcium influx. One major concern for using Mn 2+ is getting quantitative information over a range of concentrations. Therefore, in this study, a T, mapping method has been implemented for cardiac manganese-enhanced MRI (MEMRI) to increase the sensitivity and enable the quantitative estimate of a range of concentrations

Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation

Monitoring dynamic alterations in calcium homeostasis by T1-weighted and T1-mapping cardiac manganese-enhanced MRI in a murine myocardial infarction model

Manganese has been used as a T-weighted MRI contrast agent in a variety of applications. Because manganese ions (Mn) enter viable myocardial cells via voltage-gated Ca channels, manganese-enhanced MRI is sensitive to the viability and inotropic state of the heart. In spite of the established importance of Ca regulation in the heart both before and after myocardial injury, monitoring strategies to assess Ca homeostasis in affected cardiac tissues are limited. This study implements a T-mapping method to obtain quantitative information both dynamically and over a range of MnCl infusion doses. To optimize the current Mn infusion protocols, we performed both dose-dependent and temporal washout studies. A non-linear relationship between infused MnCl solution dose and increase in left ventricular wall relaxation rate (DR) was observed. Control mice also exhibited significant Mn clearance over time, with a decrease in DRof ~50% occurring in just 2.5 h. The complicated efflux time dependence possibly suggests multiple efflux mechanisms. With the use of the measured relationship between infused Mn dose, DR, and inductively coupled plasma mass spectrometry data analysis provided a means of estimating the absolute heart Mn concentration in vivo. We show that this technique has the sensitivity to observe or monitor potential alterations in Ca handling in vivo because of the physiological remodeling after myocardial infarction. Left ventricular free wall DR values were significantly lower (P = 0.005) in the adjacent zone, surrounding the injured myocardial tissue, than in healthy tissue. This inferred reduction in Mn concentration can be used to estimate potentially salvageable myocardium in vivo for future treatment or evaluation of disease progression

Effect of P2X7 inhibition on cortical lesion volume after TBI.

<p>Quantification of cortical lesion volume following placebo or BBG (50 mg/kg, i.p) treatment. Lesion volume is expressed as mm³. Data were analyzed using a t-test (*p<0.05 vs. placebo).</p

Antagonism of P2X7 reduces cerebral edema after TBI.

<p>(<b>A</b>) A single intravenous bolus of 50 mg/kg BBG provided 15 minutes prior to TBI, significantly reduced the development of cerebral edema at 24h post-TBI, as measured by brain water content. (<b>B</b>) A single intravenous bolus of 50–100 mg/kg BBG administered 0.5h after TBI significantly reduced cerebral edema at 24h post-TBI. (<b>C</b>) Administration of a single intravenous bolus of 50 mg/kg BBG reduced cerebral edema when administered 1h or 4h after injury. This effect was lost if post-treatment was delayed beyond 8h from the time of injury. (<b>D</b>) Prophylactic treatment with BBG in the drinking water for 7 days reduced edema at 24h post-TBI at a concentration of 25 mg/ml but not 10mg/ml. Comparisons within each hemisphere between different treatments groups were done using a one-way ANOVA followed by Dunnett's post-hoc test (*p<0.05, **p<0.01, ***p<0.001 vs. the ipsilateral hemisphere in sham-operated mice). No significant differences in cerebral edema were observed between groups in the contralateral hemisphere. Data are represented as the mean ± SEM from 5–6 mice/group.</p