Acute drivers of neuroinflammation in traumatic brain injury

Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology.Immune cells respond to acute signals from damaged cells,initiate neuroinflammation,and drive the pathological consequences over time.Importantly,the mechanism(s)of injury,the location of the immune cells within the brain,and the animal species all contribute to immune cell behavior following traumatic brain injury.Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration.Within this paper,we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.

4-Amino-1,8-naphthalimide based fluorescent photoinduced electron transfer (PET) pH sensors as liposomal cellular imaging agents: The effect of substituent patterns on PET directional quenching

Four new fluorescent sensors(1-4)based on the 4-amino-1,8-naphthalimide fluorophores(Naps)have been synthesized based on the classical fluorophore-spacer-receptor model.These four compounds all gave rise to emission bands centred at ca.535 nm,which were found to be highly pH dependent,the emission being‘switched on’in acidic media,while being quenched due to PET from the amino moieties to the excited state of the Nap at more alkaline pH.The luminescent pH dependence for these probes was found to be highly dependent on the substitution on the imide site,as well as the polyamine chain attached to the position 4-amino moiety.In the case of sensor 2 the presence of the 4-amino-aniline dominated the pH dependent quenching.Nevertheless,at higher pH,PET quenching was also found to occur from the polyamine site.Hence,2 is better described as a receptor1-spacer1-fluorophore-spacer2-receptor2 system,where the dominant PET process is due to(normally less favourable)‘directional’PET quenching from the 4-amino-aniline unit to the Nap site.Similar trends and pH fluorescence dependences were also seen for 3 and 4.These compounds were also tested for their imaging potential and toxicity against HeLa cells(using DRAQ5 as nuclear stain which does now show pH dependent changes in acidic and neutral pH)and the results demonstrated that these compounds have reduced cellular viability at moderately high concentrations(with IC50 values between ca.8-30μmol?L^?1),but were found to be suitable for intracellular pH determination at 1μmol?L^?1 concentrations,where no real toxicity was observed.This allowed us to employ these as lysosomal probes at sub-toxic concentrations,where the Nap based emission was found to be pH depended,mirroring that seen in aqueous solution for 1-4,with the main fluorescence changes occurring within acidic to neutral pH.