ABSTRACT
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.
Incorporating civic engagement in the undergraduate curriculum has become a goal in higher education generally and the communication discipline specifically. Given this emerging priority, we offer a ...framework that integrates civic engagement in the communication classroom and meets students and instructors needs, experience, and goals. Drawing on a case study of a large multi-section course, we detail three levels of civic engagement integration: micro, meso, and macro. This multileveled approach to civic engagement provides varied opportunities for students and instructors alike to learn how communication concepts can be applied in order to address social issues and advocate for change.
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 < 0.05). fMRS results showed a significant decrease in glutamate change with stimulation (ΔGlu) with age (P < 0.05), and ΔGlu 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.
•Describe a novel anaesthetic protocol to examine age-related alterations in neuronal activity in rodents.•Size of the BOLD signal in the somatosensory cortex decreased with age.•Reduction in glutamate turnover with age.•No change in resting CBF with age.
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.
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.
Experimental stroke in rodents, via middle cerebral artery occlusion (MCAO), can be associated with a negative impact on wellbeing and mortality. In hypertensive rodents, pre-stroke craniotomy ...increased survival and decreased body weight loss post-MCAO. Here we determined the effect, in normotensive Sprague-Dawley rats following 60 minutes MCAO, with or without pre-surgical craniotomy, on post-stroke outcomes in terms of weight loss, neurological deficit, lesion volume and functional outcomes. There was no effect of pre-stroke craniotomy on indicators of wellbeing including survival rate (P = 0.32), body weight loss (P = 0.42) and neurological deficit (P = 0.75). We also assessed common outcome measures following experimental stroke and found no effect of pre-stroke craniotomy on lesion volume as measured by T2-weighted MRI (P = 0.846), or functional performance up to 28 days post-MCAO (staircase test, P = 0.32; adhesive sticker test, P = 0.49; cylinder test, P = 0.38). Thus, pre-stroke craniotomy did not improve animal welfare in terms of body weight loss and neurological deficit. However, it is important, given that a number of drug delivery studies utilise the craniotomy procedure, to note that there was no effect on lesion volume or functional outcome following experimental stroke.
Animal models are essential for understanding the pathology of stroke and investigating potential treatments. However,
stroke models are associated, particularly in mice, with high variability in ...lesion volume. We investigated whether a surgical refinement where reperfusion is not reliant on the Circle of Willis reduced outcome variability. Mice underwent 60 min of transient middle cerebral artery occlusion avoiding ligation of the external carotid artery. During reperfusion, the common carotid artery was either ligated (standard approach), or it was repaired to allow re-establishment of blood flow through the common carotid artery. All mice underwent MRI scanning for assessment of infarct volume, apparent diffusion coefficient and fractional anisotropy, along with terminal assessment of infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Repairing the common carotid artery following middle cerebral artery occlusion enhanced reperfusion (
<0.01) and reduced the variability seen in both total (histological analysis,
=0.008; T2-weighted MRI,
=0.015) and core (diffusion tensor MRI,
=0.043) lesion volume. Avoiding external carotid artery ligation may improve animal wellbeing, through reduced weight loss, while using an alternative surgical approach that enabled reperfusion through the common carotid artery decreased the variability in lesion volume seen within groups.
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, 24 h and 48 h post-MCAO.
Results: CCA ligation reduced cerebral perfusion in the ipsilateral hemisphere compared to baseline (102.3 ± 4.57%) at 24 h (85.13 ± 16.09%; P < 0.01) and 48 h (75.04 ± 12.954%; P < 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 24 h (102.83 ± 8.41%; P < 0.05) and 48 h (102.13 ± 9.34%; P < 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.
Collaborative relationships between families and teachers of elementary-aged children are complicated by teachers’ lack of training for family engagement and by hierarchical and racialized power ...differentials. Home visiting can create a space for teachers to center and honor families’ ways of knowing and being, but those home visits need to be conducted in ways specifically intended to build relationships with families; otherwise, the visits can do damage. In this descriptive exploratory study, we examined how teachers responded to families’ openings during home visits. We articulate a theory that describes actions teachers can employ to build rapport, particularly across difference. This work has implications for research on family engagement and for teacher preparation for home visiting.
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