[Show abstract][Hide abstract] ABSTRACT: Arterial spin labelling (ASL) is increasingly available for noninvasive cerebral blood flow (CBF) measurement in stroke research. Here, a pseudo-continuous ASL technique (pCASL) was evaluated against (99m)Tc-D, L-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) autoradiography in a rat stroke model. The (99m)Tc-HMPAO was injected (intravenously, 225 MBq) during pCASL acquisition. The pCASL and (99m)Tc-HMPAO autoradiography CBF measures, relative to the contralateral hemisphere, were in good agreement across the spectrum of flow values in normal and ischemic tissues. The pCASL-derived quantitative regional CBF values (contralateral: 157 to 177 mL/100 g per minute; ipsilateral: 9 to 104 mL/100 g per minute) were consistent with the literature values. The data show the potential utility of pCASL for CBF assessment in a rat stroke model.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 04/2012; 32(6):973-7. DOI:10.1038/jcbfm.2012.19 · 5.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T(2)(*) magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O(2) induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T(2)(*) signal. Therefore, we investigated replacing 100% O(2) OC with 40% O(2) OC (5 minutes 40% O(2) versus 100% O(2)) and determined the effects on blood pressure (BP), CBF, tissue pO(2), and T(2)(*) signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded pO(2) and CBF during 40% O(2) (n=6) or 100% O(2) (n=8) OC. In a separate MRI study, T(2)(*) signal change to 40% O(2) (n=6) and 100% O(2) (n=5) OC was compared. Oxygen challenge (40% and 100% O(2)) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra pO(2) levels by 80% and 144%, respectively. T(2)(*) signal significantly increased by 4.56% ± 1.61% and 8.65% ± 3.66% in penumbra compared with 2.98% ± 1.56% and 2.79% ± 0.66% in contralateral cortex and 1.09% ± 0.82% and -0.32% ± 0.67% in ischemic core, respectively. For diagnostic imaging, 40% O(2) OC could provide sufficient T(2)(*) signal change to detect penumbra with limited influence in BP and CBF.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 05/2011; 31(8):1799-806. DOI:10.1038/jcbfm.2011.65 · 5.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a potential therapeutic target to improve mood and socio-affiliative behaviors in patients with profound social deficits and/or drug addiction.
[Show abstract][Hide abstract] ABSTRACT: Dopamine and oxytocin have established roles in the central regulation of penile erection in rats; however, the neural circuitries involved in a specific erectile context and the interaction between dopamine and oxytocin mechanisms remain to be elucidated. The medial preoptic area (MPOA), supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus may serve as candidate sites because they contain oxytocin cells, receive dopaminergic inputs and have been implicated in mediating masculine sexual behavior. Double immunofluorescence revealed that substantial numbers of oxytocin cells in the MPOA, SON and PVN possess dopamine D(2), D(3) and D(4) receptors. In anaesthetized rats, using intracavernous pressure as a physiological indicator of erection, blockade of lumbosacral oxytocin receptors (UK, 427843) reduced erectile responses to a nonselective dopamine agonist (apomorphine), suggesting that dopamine recruits a paraventriculospinal oxytocin pathway. In conscious males in the absence of a female, penile erection elicited by a D(2)/D(3) (Quinelorane) but not D(4) (PD168077) agonist was associated with activation of medial parvocellular PVN oxytocin cells. In another experiment where males were given full access to a receptive female, a D(4) (L-745870) but not D(2) or D(3) antagonist (L-741626; nafadotride) inhibited penile erection (intromission), and this was correlated with SON magnocellular oxytocin neuron activation. Together, the data suggest dopamine's effects on hypothalamic oxytocin cells during penile erection are context-specific. Dopamine may act via different parvocellular and magnocellular oxytocin subpopulations to elicit erectile responses, depending upon whether intromission is performed. This study demonstrates the potential existence of interaction between central dopamine and oxytocin pathways during penile erection, with the SON and PVN serving as integrative sites.
European Journal of Neuroscience 12/2009; 30(11):2151-64. DOI:10.1111/j.1460-9568.2009.06999.x · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dopamine and oxytocin are two key neuromodulators involved in reproductive behaviours, such as mating and maternal care. Much evidence underlies their separate roles in such behaviours, but particularly in sexual behaviour. It is generally believed that central dopaminergic and oxytocinergic systems work together to regulate the expression of penile erection, but relatively little is known regarding how they interact. Thus, this review aims to discuss neuroanatomical proof, neuromodulator secretory profiles in the hypothalamus and behavioural pharmacological evidence which support a dopamine-oxytocin link in three hypothalamic nuclei that have been implicated in sexual behaviour, namely the medial preoptic nucleus, supraoptic nucleus and paraventricular nucleus (PVN). We also aim to provide an overview of potential dopamine-mediated transduction pathways that occur within these nuclei and are correlated with the exhibition of penile erection. The PVN provides the most convincing evidence for a dopamine-oxytocin link and it is becoming increasingly apparent that parvocellular oxytocinergic neurons in the PVN, in part, mediate the effects of dopamine to elicit penile erection. However, while we show that oxytocin neurons express dopamine receptors, other evidence on whether dopaminergic activation of PVN oxytocin cells involves a direct and/or indirect mechanism is inconclusive and further evidence is required to establish whether the two systems interact synergistically or sequentially in the regulation of penile erection.
Progress in brain research 01/2008; 170:277-90. DOI:10.1016/S0079-6123(08)00423-8 · 2.83 Impact Factor