Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Here, we developed a microfluidic-assisted blood-brain barrier (BBB) device and tested the effects of omega-3 fatty acids on neuroimmune interactions after orthopaedic surgery. METHODS: A microfluidic-assisted BBB device was established using primary human cells. Tight junction proteins, vascular cell adhesion molecule 1 (VCAM-1), BBB permeability, and astrocytic networks were assessed after stimulation with interleukin (IL)-1ß and in the presence or absence of a clinically available omega-3 fatty acid emulsion (Omegaven®; Fresenius Kabi, Bad Homburg, Germany). Mice were treated 1 h before orthopaedic surgery with 10 µl g-1 body weight of omega-3 fatty acid emulsion i.v. or equal volumes of saline. Changes in pericytes, perivascular macrophages, BBB opening, microglial activation, and inattention were evaluated. RESULTS: Omega-3 fatty acids protected barrier permeability, endothelial tight junctions, and VCAM-1 after exposure to IL-1ß in the BBB model. In vivo studies confirmed that omega-3 fatty acid treatment inhibited surgery-induced BBB impairment, microglial activation, and delirium-like behaviour. We identified a novel role for pericyte loss and perivascular macrophage activation in mice after surgery, which were rescued by prophylaxis with i.v. omega-3 fatty acids. CONCLUSIONS: We present a new approach to study neuroimmune interactions relevant to perioperative recovery using a microphysiological BBB platform. Changes in barrier function, including dysregulation of pericytes and perivascular macrophages, provide new targets to reduce postoperative delirium.

The prevalence and cognitive profile of sequence-space synaesthesia.

People with sequence-space synaesthesia visualize sequential concepts such as numbers and time as an ordered pattern extending through space. Unlike other types of synaesthesia, there is no generally agreed objective method for diagnosing this variant or separating it from potentially related aspects of cognition. We use a recently-developed spatial consistency test together with a novel questionnaire on naïve samples and estimate the prevalence of sequence-space synaesthesia to be around 8.1% (Study 1) to 12.8% (Study 2). We validate our test by showing that participants classified as having sequence-space synaesthesia perform differently on lab-based tasks. They show a spatial Stroop-like interference response, they show enhanced detection of low visibility Gabor stimuli, they report more use of visual imagery, and improved memory for certain types of public events. We suggest that sequence-space synaesthesia develops from a particular neurocognitive profile linked both to greater visual imagery and enhanced visual perception.

An autistic-like profile of attention and perception in synaesthesia.

Synaesthesia and autism are two neurodevelopmental conditions that have been shown to co-occur more than expected by chance. The studies reported here test the hypothesis that increased sensory sensitivity and enhanced Attention-to-detail are core cognitive features that are shared between them. In Study 1, we administer self-report measures of sensory sensitivity and autistic traits (the Autism Spectrum Quotient, AQ) to a large heterogeneous sample of synaesthetes. Both sensory sensitivity and the Attention-to-detail subscale of the AQ show a "dose-like" relationship with synaesthesia: namely, more kinds of synaesthesia is related to a greater shift up the autistic spectrum. Study 2 uses two objective measures of visual perception/attention linked to autistic traits: Change Blindness and detection of local embedded figures. Both measures are shown here to be sensitive to the Attention-to-detail subscale of the AQ, and synaesthetes outperformed controls on both tasks. Synaesthetes appear to occupy a specific cognitive niche of having autistic-like traits linked to enhanced perception and attention. Whilst these typically occur in the absence of the traditional impairments that define autism, they may carry the cost of increased vulnerability to clinical levels of autism (Odds Ratio = 2.07).