44 research outputs found

    Contributions and complexities from the use of in-vivo animal models to improve understanding of human neuroimaging signals.

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    Many of the major advances in our understanding of how functional brain imaging signals relate to neuronal activity over the previous two decades have arisen from physiological research studies involving experimental animal models. This approach has been successful partly because it provides opportunities to measure both the hemodynamic changes that underpin many human functional brain imaging techniques and the neuronal activity about which we wish to make inferences. Although research into the coupling of neuronal and hemodynamic responses using animal models has provided a general validation of the correspondence of neuroimaging signals to specific types of neuronal activity, it is also highlighting the key complexities and uncertainties in estimating neural signals from hemodynamic markers. This review will detail how research in animal models is contributing to our rapidly evolving understanding of what human neuroimaging techniques tell us about neuronal activity. It will highlight emerging issues in the interpretation of neuroimaging data that arise from in-vivo research studies, for example spatial and temporal constraints to neuroimaging signal interpretation, or the effects of disease and modulatory neurotransmitters upon neurovascular coupling. We will also give critical consideration to the limitations and possible complexities of translating data acquired in the typical animals models used in this area to the arena of human fMRI. These include the commonplace use of anaesthesia in animal research studies and the fact that many neuropsychological questions that are being actively explored in humans have limited homologues within current animal models for neuroimaging research. Finally we will highlighting approaches, both in experimental animals models (e.g. imaging in conscious, behaving animals) and human studies (e.g. combined fMRI-EEG), that mitigate against these challenges

    Towards an Understanding of Tinnitus Heterogeneity

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    Radiolabelled Molecules for Brain Imaging with PET and SPECT

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    Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo molecular imaging methods which are widely used in nuclear medicine for diagnosis and treatment follow-up of many major diseases. These methods use target-specific molecules as probes, which are labeled with radionuclides of short half-lives that are synthesized prior to the imaging studies. These probes are called radiopharmaceuticals. The use of PET and SPECT for brain imaging is of special significance since the brain controls all the body’s functions by processing information from the whole body and the outside world. It is the source of thoughts, intelligence, memory, speech, creativity, emotion, sensory functions, motion control, and other important body functions. Protected by the skull and the blood–brain barrier, the brain is somehow a privileged organ with regard to nutrient supply, immune response, and accessibility for diagnostic and therapeutic measures. Invasive procedures are rather limited for the latter purposes. Therefore, noninvasive imaging with PET and SPECT has gained high importance for a great variety of brain diseases, including neurodegenerative diseases, motor dysfunctions, stroke, epilepsy, psychiatric diseases, and brain tumors. This Special Issue focuses on radiolabeled molecules that are used for these purposes, with special emphasis on neurodegenerative diseases and brain tumors

    Diffusion tensor imaging and resting state functional connectivity as advanced imaging biomarkers of outcome in infants with hypoxic-ischaemic encephalopathy treated with hypothermia

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    Therapeutic hypothermia confers significant benefit in term neonates with hypoxic-ischaemic encephalopathy (HIE). However, despite the treatment nearly half of the infants develop an unfavourable outcome. Intensive bench-based and early phase clinical research is focused on identifying treatments that augment hypothermic neuroprotection. Qualified biomarkers are required to test these promising therapies efficiently. This thesis aims to assess advanced magnetic resonance imaging (MRI) techniques, including diffusion tensor imaging (DTI) and resting state functional MRI (fMRI) as imaging biomarkers of outcome in infants with HIE who underwent hypothermic neuroprotection. FA values in the white matter (WM), obtained in the neonatal period and assessed by tract-based spatial statistics (TBSS), correlated with subsequent developmental quotient (DQ). However, TBSS is not suitable to study grey matter (GM), which is the primary site of injury following an acute hypoxic-ischaemic event. Therefore, a neonatal atlas-based automated tissue labelling approach was applied to segment central and cortical grey and whole brain WM. Mean diffusivity (MD) in GM structures, obtained in the neonatal period correlated with subsequent DQ. Although the central GM is the primary site of injury on conventional MRI following HIE; FA within WM tissue labels also correlated to neurodevelopmental performance scores. As DTI does not provide information on functional consequences of brain injury functional sequel of HIE was studied with resting state fMRI. Diminished functional connectivity was demonstrated in infants who suffered HIE, which associated with an unfavourable outcome. The results of this thesis suggest that MD in GM tissue labels and FA either determined within WM tissue labels or analysed with TBSS correlate to subsequent neurodevelopmental performance scores in infants who suffered HIE treated with hypothermia and may be applied as imaging biomarkers of outcome in this population. Although functional connectivity was diminished in infants with HIE, resting state fMRI needs further study to assess its utility as an imaging biomarker following a hypoxic-ischaemic brain injury.Open Acces

    Periodic assessment of (ET-1) and Nitric Oxide (NO) in hypertensive disorders of pregnancy (HDP)

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    INTRODUCTION Hypertensive Disorders of Pregnancy (HDP) is an independent risk factor of cardiovascular (CVS) disease. Endothelin-1 (ET-1), a potent vasoconstrictor, has been identified as a pivotal mediator in both essential hypertension and HDP. Disturbances in Nitric Oxide (NO) bioavailability found in endothelial dysfunction may increase susceptibility to cardiovascular diseases. METHODOLOGY Thirty six pregnant women at 30-36 weeks period of gestation from the following categories (i) pregnancy induced hypertension (PIH) (ii) chronic hypertension during pregnancy (CH) and (iii) normal pregnant women (Control). Blood pressure indices measurements and sample collection was done at antepartum (30-36 weeks), post partum (8 weeks and 12 weeks). Endothelin-1 and serum NO were measured using the Human ET-1 (Endothelin-1) and NO ELISA Kit. RESULTS All blood pressure indices were significantly higher in HDP patients compared to control during antenatal and post partum periods. Serum ET-1 was significantly higher in patients with HDP compared to control during antenatal until 3 months post partum. This was accompanied by significantly lower levels of serum NO in HDP patients. CONCLUSION Persistently high levels of ET-1 and low levels of NO up to 3 months post partum in patients with history of HDP indicate presence of persistent endothelial dysfunction despite BP normalisation in PIH patients. Long term NO/ET-1 imbalance may account for the increased CVS disease risk

    Oxytocin neurone activity and release following administration of Melanotan-II in anaesthetised rats

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    Oxytocin release within the brain modulates several social behaviours in animals and humans. Moreover, low central oxytocin content has been linked to neuropsychiatric disorders, such as anxiety and autism. The exogenous administration of oxytocin has been proposed for therapeutic treatment, but oxytocin does not cross the blood-brain barrier (BBB) in physiologically significant amounts. An alternative approach to oxytocin administration is to stimulate central oxytocin release using melanocortins. Central administration of the naturally occurring melanocortin, α-MSH, has been shown to trigger somatodendritic oxytocin release in vitro. Unfortunately, endogenous melanocortins also do not penetrate the BBB in neuroactive amounts. In this study, I investigated whether systemic administration of synthetic melanocortin receptor 3/4 (MC3/4) agonist, Melanotan-II (MT-II), affects oxytocin neuronal activity and secretion in anaesthetised rats. I hypothesised that systemic administration of MT-II directly (centrally) acts on magnocellular oxytocin neurones to trigger somatodendritic oxytocin release from neurones of the supraoptic nucleus (SON) of the hypothalamus in vivo. Firstly, using double immunohistochemistry against Fos protein, a widely used marker for neural activity, and oxytocin, I showed that intravenous (i.v.; 1 mg/kg), but not intranasal (1 and 30 μg rat), administration of MT-II markedly induced Fos expression in magnocellular oxytocin neurones of the SON and paraventricular nuclei (PVN) of the hypothalamus, and this response was prevented by prior intracerebroventricular (i.c.v.) administration of the melanocortin antagonist, SHU-9119 (1 μg rat). In addition, brain areas receiving peripheral inputs which are involved in the regulation of oxytocin and vasopressin release were also analysed, showing that i.v. MT-II significantly increased Fos expression in the nucleus tractus solitarii (NTS), but not in circumventricular organs of the anteroventral third ventricle (AV3V) region. MT-II-induced Fos in the NTS was not prevented by the i.c.v. melanocortin antagonist. Then, using in vivo electrophysiology, I investigated whether i.v. administration of MT-II affects the electrical activity of SON neurones. Extracellular single-unit recordings from identified magnocellular neurones of the SON showed that MT-II significantly increased the firing rate in oxytocin neurones, however, no significant changes in firing rate were detected in vasopressin neurones. Finally, in vivo oxytocin release experiments showed that i.v. administration of MT-II did not trigger somatodendritic oxytocin release within the SON as measured by microdialysis and subsequent radioimmunoassay. Interestingly, the i.c.v. administration of MT-II (1 μg rat) also failed to trigger oxytocin release within the SON. The analysis of oxytocin content in plasma revealed that the change in oxytocin concentration was significantly greater in i.v. MT-II injected rats compared to vehicle-injected rats. Taken together, these results show that after i.v., but not intranasal, administration of MT-II, the activity of magnocellular neurones of the SON is increased. As previous studies showed that SON oxytocin neurones are inhibited in response to direct application of melanocortin agonists, the actions of i.v. MT-II are likely to be mediated, at least in part, indirectly by activation of inputs from the caudal brainstem
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