The effects of locomotion on sensory-evoked haemodynamic responses in the cortex of awake mice

Investigating neurovascular coupling in awake rodents is becoming ever more popular due, in part, to our increasing knowledge of the profound impacts that anaesthesia can have upon brain physiology. Although awake imaging brings with it many advantages, we still do not fully understand how voluntary locomotion during imaging affects sensory-evoked haemodynamic responses. In this study we investigated how evoked haemodynamic responses can be affected by the amount and timing of locomotion. Using an awake imaging set up, we used 2D-Optical Imaging Spectroscopy (2D-OIS) to measure changes in cerebral haemodynamics within the sensory cortex of the brain during either 2s whisker stimulation or spontaneous (no whisker stimulation) experiments, whilst animals could walk on a spherical treadmill. We show that locomotion alters haemodynamic responses. The amount and timing of locomotion relative to whisker stimulation is important, and can significantly impact sensory-evoked haemodynamic responses. If locomotion occurred before or during whisker stimulation, the amplitude of the stimulus-evoked haemodynamic response was significantly altered. Therefore, monitoring of locomotion during awake imaging is necessary to ensure that conclusions based on comparisons of evoked haemodynamic responses (e.g., between control and disease groups) are not confounded by the effects of locomotion.

Effect of drug interventions on cerebral haemodynamics in ischaemic stroke patients

The ischaemic penumbra is sensitive to alterations in cerebral perfusion. A myriad of drugs are used in acute ischaemic stroke (AIS) management, yet their impact on cerebral haemodynamics is poorly understood. As part of the Cerebral Autoregulation Network led INFOMATAS project ( Identifying New Targets for Management and Therapy in Acute Stroke), this paper reviews some of the most common drugs a patient with AIS will come across and their potential influence on cerebral haemodynamics with a particular focus being on cerebral autoregulation (CA). We first discuss how compounds that promote clot lysis and prevent clot formation could potentially impact cerebral haemodynamics, before focusing on how the different classes of antihypertensive drugs can influence cerebral haemodynamics. We discuss the different properties of each drug and their potential impact on cerebral perfusion and CA. With emerging interest in CA status of AIS patients, either during or soon after treatment when timely reperfusion and salvageable tissue is at its most critical, the properties of these pharmacological agents may be relevant for modelling cerebral perfusion accuracy and for setting individualised treatment strategies.

Investigating the association between depressive disorders and cerebral haemodynamics

AimsAlterations in cerebral blood flow (CBF) may contribute to the development of depression, and serve as a novel biomarker. The aim of this review is to summarise and synthesise the available evidence on alterations in cerebral haemodynamics in depressive disorders relative to healthy control populations.MethodMEDLINE (1946- present), EMBASE (1947– present), Web of Science (1970–present), PsycINFO (1984–present), CINAHL (1976–present) and CENTRAL were searched using a predefined search strategy. Studies which compared the cerebral haemodynamics of adult patients (>18 years old) with depressive disorders against healthy controls (HC), by any imagining modality, were included. Studies with varying severity and chronicity of depressive disorder were included. A meta-analysis was conducted in four groups: 1) CBF (ml/min/100g) 2) Cerebral blood flow velocity (CBFv) (cm/s) 3) Combined CBF and CBFv 4) Ratio of uptake of radiotracer. A random effects model was used and heterogeneity and publication bias were assessed. Data are presented as mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed.Result87 studies met the inclusion criteria. CBF (ml/min/100g) was significantly reduced in patients with depression compared to HC (15 studies, 538 patients, 416 HC, MD: −2.24 (95% CI −4.12, −0.36), p = 0.02, I2 = 64%). There were no statistically significant differences between patients and controls in the other three outcomes. CBFv (cm/s): 6 studies, 305 patients, 198 HC, MD: −1.23 (95% CI −6.10, 3.64, p = 0.62, I2 = 65%. Combined CBF and CBFv: 20 studies, 804 patients, 573 HC, SMD: −0.16 (95% CI −0.32, 0.01), p = 0.06 I2 = 51%. Ratio of uptake of radiotracer: 3 studies, 60 patients, 53 HC, MD: −0.11 (95% CI −0.11, 0.11), p = 1.00, I2 = 0%). The narrative synthesis revealed varying results, with many studies identifying a decrease in CBF in depressed patients compared to controls, but other studies identifying an increase, or mixed results. Multiple regions of impairment were identified, including the anterior cingulate cortex and prefrontal cortex.ConclusionThere was a statistically significant reduction in CBF in depressed patients compared to controls. The narrative synthesis revealed varying results, however specific regions of interest have been identified. Further research is needed to explore the effect of antidepressant medication, utilising different imaging modalities, and at different levels of disease severity.