Although much is known about the perceptual characteristics of tinnitus, its neural origins remain poorly understood. We investigated the pattern of neural activation in central auditory structures using positron emission tomography (PET) imaging in a rat model of salicylate-induced tinnitus. Awake rats were injected with the metabolic tracer, fluorine-18 fluorodeoxyglucose (FDG), once in a quiet state (baseline) and once during salicylate-induced tinnitus. Tinnitus was verified using a behavioral technique. Brain imaging was performed using a high-resolution microPET scanner. Rats underwent magnetic resonance imaging (MRI) and reconstructed MRI and microPET images were fused to identify brain structures. FDG activity in brain regions of interest were quantified and compared. MicroPET imaging showed that FDG activity in the frontal pole was stable between baseline and tinnitus conditions, suggesting it was metabolically inert during tinnitus. Inferior colliculi (p=0.03) and temporal cortices (p=0.003) showed significantly increased FDG activity during tinnitus relative to baseline; activity in the colliculi and temporal cortices increased by 17% ± 21% and 29% ± 20%, respectively. FDG activity in the thalami also increased during tinnitus, but the increase did not reach statistical significance (p=0.07). Our results show increased metabolic activity consistent with neuronal activation in inferior colliculi and auditory cortices of rats during salicylate-induced tinnitus. These results are the first to show that microPET imaging can be used to identify central auditory structures involved in tinnitus and suggest that microPET imaging might be used to evaluate the therapeutic potential of drugs to treat tinnitus.
Different strategies for treatment and prevention of Alzheimer’s disease (AD) are currently under investigation, including passive immunization with anti-amyloid β (anti-Aβ) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of Aβ-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z
SYM73
-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z
SYM73
affibody for sequestering of monomeric Aβ-peptides and an ABD for extension of its
in vivo
half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z
SYM73
-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported
in vivo
investigation of a systemically delivered scaffold protein against monomeric Aβ, demonstrating a therapeutic potential for prevention of AD.
To elucidate the after-effect of exercise on left ventricular (LV) function, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were evaluated at 1 h after exercise and at rest by technetium-99m tetrofosmin gated myocardial single-photon emission tomography (SPET) using an automated program in 53 subjects. The subjects were grouped as follows: normal scan (n = 16), ischaemia (n = 19) and infarction (n = 18), based on the interpretation of perfusion images. Postexercise LVEF did not differ from resting LVEF in the groups with normal scan and infarction. In patients with ischaemia, postexercise EDV (90+/-17 ml, mean +/-SD) and ESV (44+/-15 ml) were significantly higher than EDV (84+/-15 ml, P = 0.001) and ESV (36+/-14 ml, P<0.0005) at rest. LVEF was significantly depressed 1 h after exercise (53%+/-9% vs 58%+/-9%, P<0.0001). In ischaemic patients with depressed postexercise LVEF, LVEF difference between rest and postexercise showed a significant correlation with the sum of defect scores, which were reversible from exercise to rest perfusion images (r = 0.92, P<0.0001). These results indicate that exercise-induced LV dysfunction (myocardial stunning) continues for at least 1 h in ischaemic patients and that the extent of LVEF depression is determined by the severity of ischaemia.
Significant postexercise LV regional dysfunction, consistent with the concept of stunning, occurs in the region of severe ischemia. The incidence and magnitude of regional stunning are determined by the severity of ischemia. For the detection of stunning in gated SPECT, LV regional dysfunction may be more sensitive than global dysfunction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.