397 research outputs found
Sexual dimorphism following in vitro ischemia in the response to neurosteroids and mechanisms of injury
Social functioning as a mediator between Developmental Language Disorder (DLD) and emotional problems in adolescents
Adolescents with Developmental Language Disorder (DLD) are at risk for increased feelings of anxiety and depression compared to their typically developing (TD) peers. However, the underlying pathways involved in this relationship are unclear. In this initial study of the ‘social mediation hypothesis’ we examine social functioning as a mediator of emotional problems in a cross-sectional sample of adolescents with DLD and age- and sex-matched controls. Preliminary data from twenty-six participants with DLD and 27 participants with typical language development (TLD, 11-17 years) were compared on self- and parent-reported measures of social functioning and emotional outcomes. There was little evidence of group differences in self-reported social functioning and emotional outcomes, but parent-report of SDQ Peer Problems and Emotional Problems in the DLD group was significantly higher than in the TLD group. Parent-reported peer problems mediated parent-reported emotional problems, accounting for 69% of the relationship between DLD status and emotional problems. Parents of adolescents with DLD, but not adolescents themselves, report significantly higher peer and emotional problems compared to TLD peers. The hypotheses generated from these novel data suggest further investigation into adolescents’ perceptions of socioemotional difficulties and friendships should be examined
Are older people prescribed antidepressants on the basis of fewer symptoms of depression, and for longer periods of time? A survey of 1825 New Zealanders
Aims: To determine whether older people are prescribed antidepressants at lower levels of
depression and with fewer symptoms, and whether they are more likely to engage in chronic
usage.
Methods: An online survey about experiences with, and opinions about, depression and
antidepressants, was completed by 1,825 New Zealand adults who had been prescribed
antidepressants in the preceding five years.
Results: Participants over 55 were prescribed antidepressants with significantly fewer
symptoms and were significantly less likely to meet DSM criteria for depression. They were
also significantly more likely to have used the drugs for three years and still be using them.
Conclusions: Prescribing physicians and their older patients might benefit from discussing
the pros and cons of antidepressants (including the additional risk factors with this age
group) and the alternatives; and, if prescription does occur, careful monitoring to avoid
unnecessary, potentially damaging, long-term use is recommended
Social Cognition in Adolescents with Developmental Language Disorder (DLD): Evidence from the Social Attribution Task
Social cognition impairments may explain social, emotional and behavioural difficulties (SEBD) in individuals with Developmental Language Disorder (DLD). In a novel approach, the Social Attribution Task (SAT) was used to examine this association. SAT narratives were coded from 53 participants [n = 26 DLD; n = 27 typical language development (TLD)] matched on age (Mage = 13;6) and gender (35.9% female). Parents reported SEBD. Adolescents with DLD performed worse than their TLD peers on the majority of SAT indices and had higher peer (d = 1.09) and emotional problems (d = .75). There was no association between social cognition abilities and SEBD. These exploratory findings suggest social cognition should be further examined in this population
Improved reperfusion following alternative surgical approach for experimental stroke in mice
Background: Following ischemic stroke, recanalisation and restoration of blood flow to the affected area of the brain is critical and directly correlates with patient recovery. In vivo models of ischemic stroke show high variability in outcomes which may be due to variability in reperfusion. We previously reported that a surgical refinement in the middle cerebral artery occlusion (MCAO) model of stroke, via repair of the common carotid artery (CCA), removes the reliance on the Circle of Willis for reperfusion and reduced infarct variability. Here we further assess this refined surgical approach on reperfusion characteristics following transient MCAO in mice.Methods: Mice underwent 60 min of MCAO, followed by either CCA repair or ligation at reperfusion. All mice underwent laser speckle contrast imaging at baseline, 24h and 48h post-MCAO.Results: CCA ligation reduced cerebral perfusion in the ipsilateral hemisphere compared to baseline (102.3 ± 4.57 %) at 24h (85.13 ± 16.09 %; P [less than] 0.01) and 48h (75.04 ± 12.954 %; P [less than] 0.001) post-MCAO. Repair of the CCA returned perfusion to baseline (94.152 ± 2.44 %) levels and perfusion was significantly improved compared to CCA ligation at both 24h (102.83 ± 8.41 %; P [less than] 0.05) and 48h (102.13 ± 9.34 %; P [less than] 0.001) post-MCAO. Conclusions: Our findings show CCA repair, an alternative surgical approach for MCAO, results in improved ischemic hemisphere perfusion during the acute phase
Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions
Ischaemic strokes evoke blood–brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions.
Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection
Longitudinal Multimodal fMRI to Investigate Neurovascular Changes in Spontaneously Hypertensive Rats
Hypertension is an important risk factor for age‐related cognitive decline and neuronal pathologies. Studies have shown a correlation between hypertension, disruption in neurovascular coupling and cerebral autoregulation, and cognitive decline. However, the mechanisms behind this are unclear. To further understand this, it is advantageous to study neurovascular coupling as hypertension progresses in a rodent model. Here, we use a longitudinal functional MRI (fMRI) protocol to assess the impact of hypertension on neurovascular coupling in spontaneously hypertensive rats (SHRs). Eight female SHRs were studied at 2, 4, and 6 months of age, as hypertension progressed. Under an IV infusion of propofol, animals underwent fMRI, functional MR spectroscopy, and cerebral blood flow (CBF) quantification to study changes in neurovascular coupling over time. Blood pressure significantly increased at 4 and 6 months (P < .0001). CBF significantly increased at 4 months old (P < .05), in the acute stage of hypertension. The size of the active region decreased significantly at 6 months old (P < .05). Change in glutamate signal during activation, and N‐acetyl‐aspartate (NAA) signal, remained constant. This study shows that, while cerebral autoregulation is impaired in acute hypertension, the blood oxygenation‐level‐dependent (BOLD) response remains unaltered until later stages. At this stage, the consistent NAA and glutamate signals show that neuronal death has not occurred, and that neuronal activity is not affected at this stage. This suggests that neuronal activity and viability is not lost until much later, and changes observed here in BOLD activity are due to vascular effects
A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain
As the population ages, the incidence of age-related neurological diseases and cognitive decline increases. To further understand disease-related changes in brain function it is advantageous to examine brain activity changes in healthy aging rodent models to permit mechanistic investigation. Here, we examine the suitability, in rodents, of using a novel, minimally invasive anaesthesia protocol in combination with a functional MRI protocol to assess alterations in neuronal activity due to physiological aging. 11 Wistar Han female rats were studied at 7, 9, 12, 15 and 18 months of age. Under an intravenous infusion of propofol, animals underwent functional magnetic resonance imaging (fMRI) and functional magnetic resonance spectroscopy (fMRS) with forepaw stimulation to quantify neurotransmitter activity, and resting cerebral blood flow (CBF) quantification using arterial spin labelling (ASL) to study changes in neurovascular coupling over time. Animals showed a significant decrease in size of the active region with age (P [less than] 0.05). fMRS results showed a significant decrease in glutamate change with stimulation (?Glu) with age (P < 0.05), and ?Glu became negative from 12 months onwards. Global CBF remained constant for the duration of the study. This study shows age related changes in the blood oxygen level dependent (BOLD) response in rodents that correlate with those seen in humans. The results also suggest that a reduction in synaptic glutamate turnover with age may underlie the reduction in the BOLD response, while CBF is preserved
A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model
Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers
Nitric oxide synthase inhibitors in experimental stroke and their effects on infarct size and cerebral blood flow: a systematic review
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