Baraa Al-Hafez

Sympathetic Hyperinnervation and Inflammatory Cell NGF Synthesis Following Myocardial Infarction in Rats

Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and alpha-smooth muscle actin-immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we co-cultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by peri-infarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction.

A mouse model of sensorimotor controlled cortical impact: Characterization using longitudinal magnetic resonance imaging, behavioral assessments and histology

The present study establishes a new mouse model for traumatic brain injury (TBI), using an electromechanically driven linear motor impactor device to deliver a lateral controlled cortical impact (CCI) injury to the sensorimotor cortex. Lesion cavity size was measured, and inter-animal consistency demonstrated, at 14 days post injury. Qualitative information regarding damage progression over time was obtained by scanning with high field magnetic resonance imaging (MRI) at five time points following injury. Functional impairment and recovery were measured with the Rotarod, gridwalk and cylinder tests, and lesion cavity volume was measured post mortem with thionin-stained tissue sections. The study establishes the reliability of a linear-motor based device for producing repeatable damage in a CCI model, demonstrates the power of longitudinal MRI in studying damage evolution, and confirms that a simple battery of functional tests record sensorimotor impairment and recovery.

Cardiac dysfunction in the diabetic rat: quantitative evaluation using high resolution magnetic resonance imaging

BackgroundDiabetes is a major risk factor for cardiovascular disease. In particular, type 1 diabetes compromises the cardiac function of individuals at a relatively early age due to the protracted course of abnormal glucose homeostasis. The functional abnormalities of diabetic myocardium have been attributed to the pathological changes of diabetic cardiomyopathy.MethodsIn this study, we used high field magnetic resonance imaging (MRI) to evaluate the left ventricular functional characteristics of streptozotocin treated diabetic Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched controls.ResultsOur analyses of EKG gated cardiac MRI scans of the left ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in the end-systolic volume of diabetic hearts compared to controls. Mean stroke volume and ejection fraction in diabetic rats were decreased (48% and 28%, respectively) compared to controls. Further, dV/dt changes were suggestive of phase sensitive differences in left ventricular kinetics across the cardiac cycle between diabetic and control rats.ConclusionThus, the MRI analyses of diabetic left ventricle suggest impairment of diastolic and systolic hemodynamics in this rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI could be used in the evaluation of cardiac dysfunction in this rat model of type 1 diabetes.

Magnetic resonance imaging of mouse spinal cord

The feasibility of performing high‐resolution in vivo MRI on mouse spinal cord (SC) at 9.4 T magnetic field strength is demonstrated. The MR properties of the cord tissue were measured and the characteristics of water diffusion in the SC were quantified. The data indicate that the differences in the proton density (PD) and transverse relaxation time between gray matter (GM) and white matter (WM) dominate the contrast seen on the mouse SC images at 9.4 T. However, on heavily T2‐weighted images these differences result in a reversal of contrast. The diffusion of water in the cord is anisotropic, but the WM exhibits greater anisotropy and principal diffusivity than the GM. The quantitative data presented here should establish a standard for comparing similar measurements obtained from the SCs of genetically engineered mouse or mouse models of SC injury (SCI). Magn Reson Med, 2005.

Electrical stimulation of cortex improves corticospinal tract tracing in rat spinal cord using manganese-enhanced MRI.

Following bilateral injection of manganese (Mn) into the rats motor cortex, electrical stimulation of the cortex is shown to increase the transport, uptake and accumulation of Mn in the corticospinal tract (CST), as assessed by manganese-enhanced magnetic resonance imaging (MEI). T(1)-weighted gradient echo images were acquired in 3-D and displayed in different orientations to anatomically delineate the CST pathway from cortex to spinal cord (SC) at the thoracic level. T(1)-maps of the SC were produced from spin-echo based image data to demonstrate the distribution of the T(1) properties of the SC tissue and to quantitatively assess the T(1)-change occurring in the CST due to the presence of Mn therein. Implications for improving the tract tracing ability with the proposed in vivo approach and its application to spinal cord injury (SCI) research are discussed in terms of aiding future experimental investigations of neuroplasticity following an injury.

Microneurography of human median nerve

To examine the possibility of performing high‐resolution MRI (microneurography) on peripheral nerves.

Magnetic resonance angiography of rat spinal cord at 9.4 T: a feasibility study

In this study we investigated the feasibility of performing 3D time‐of‐flight magnetic resonance angiography to remotely image the arteries of rat spinal cord. Using a custom‐designed implantable radiofrequency coil, we acquired angiograms from normal and injured cords. The potential of the approach was evaluated in terms of longitudinally monitoring the vascular reorganization of spinal cord following an injury. Magn Reson Med 53:1459–1461, 2005.