Primary Objective: Treatment paradigms for traumatic brain injury (TBI) rely on invasive monitoring of intracranial pressure (ICP) for planning intervention. Optical pupillometry is a non-invasive, objective monitoring method, measuring parameters of pupillary response and displaying a scalar value – a neurological pupil index (NPi). An impaired response on NPi has been tentatively correlated with ICP, through analysis of mean/peak NPi and ICP readings. We sought to evaluate this relationship more closely. Research Design: Prospective observational. Methods and Procedures: We obtained hourly pupillometry readings, alongside ICP values, from 40 patients with TBI requiring invasive ICP monitoring. Significant events were identified for analysis based on the significant aberration of ICP or NPi. Main Outcomes and Results: On average, individuals experienced a few significant events. There was a weak relationship between ICP events and a preceding NPi event. The results show that there is a weak but statistically insignificant relationship between NPi and ICP, where reduced pupil reactivity may indicate a raised ICP. The strength of this trend appears to diminish post-decompressive surgery. Conclusions: Whilst pupillometry may not be a reliable surrogate marker for ICP, NPi may still prove to be a useful tool in a multimodal prognostic assessment of the patient with acute brain injury.

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8⁺ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.

The goal was to predict pressure reactivity index (PRx) using non-invasive transcranial Doppler (TCD) based indices of cerebrovascular reactivity, systolic flow index (Sx_a), and mean flow index (Mx_a). Continuous extended duration time series recordings of middle cerebral artery cerebral blood flow velocity (CBFV) were obtained using robotic TCD in parallel with direct intracranial pressure (ICP). PRx, Sx_a, and Mx_a were derived from high frequency archived signals. Using time-series techniques, autoregressive integrative moving average (ARIMA) structure of PRx was determined and embedded in the following linear mixed effects (LME) models of PRx: PRx ∼ Sx_a and PRx ∼ Sx_a + Mx_a. Using 80% of the recorded patient data, the LME models were created and trained. Model superiority was assessed via Akaike information criterion (AIC), Bayesian information criterion (BIC), and log-likelihood (LL). The superior two models were then used to predict PRx using the remaining 20% of the signal data. Predicted and observed PRx were compared via Pearson correlation, linear models, and Bland–Altman (BA) analysis. Ten patients had 3–4 h of continuous uninterrupted ICP and TCD data and were used for this pilot analysis. Optimal ARIMA structure for PRx was determined to be (2,0,2), and this was embedded in all LME models. The top two LME models of PRx were determined to be: PRx ∼ Sx_a and PRx ∼ Sx_a + Mx_a. Estimated and observed PRx values from both models were strongly correlated ( r > 0.9; p < 0.0001 for both), with acceptable agreement on BA analysis. Predicted PRx using these two models was also moderately correlated with observed PRx, with acceptable agreement ( r = 0.797, p = 0.006; r = 0.763, p = 0.011; respectively). With application of ARIMA and LME modeling, it is possible to predict PRx using non-invasive TCD measures. These are the first and as well as being preliminary attempts at doing so. Much further work is required.

Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system (CNS) cannot repair after the initial event is resolved. The way in which function is lost after injury is the consequence of a complex array of mechanisms that continue in the chronic phase post-injury to prevent effective neural repair. This review summarises the events after traumatic brain injury (TBI) and spinal cord injury (SCI), comprising a description of current clinical management strategies, a summary of known cellular and molecular mechanisms of secondary damage and their role in the prevention of repair. A discussion of current and emerging approaches to promote neuroregeneration after CNS injury is presented. The barriers to promoting repair after neurotrauma are across pathways and cell types and occur on a molecular and system level. This presents a challenge to traditional molecular pharmacological approaches to targeting single molecular pathways. It is suggested that novel approaches targeting multiple mechanisms or using combinatorial therapies may yield the sought-after recovery for future patients.

Apoptotic cell death within the brain represents a significant contributing factor to impaired post-traumatic tissue function and poor clinical outcome after traumatic brain injury. After irradiation with light in the wavelength range of 600–1200 nm (photobiomodulation), previous investigations have reported a reduction in apoptosis in various tissues. This study investigates the effect of 660 nm photobiomodulation on organotypic slice cultured hippocampal tissue of rats, examining the effect on apoptotic cell loss. Tissue optical Raman spectroscopic changes were evaluated. A significantly higher proportion of apoptotic cells 62.8±12.2% vs 48.6±13.7% (P<0.0001) per region were observed in the control group compared with the photobiomodulation group. After photobiomodulation, Raman spectroscopic observations demonstrated 1440/1660 cm^-1 spectral shift. Photobiomodulation has the potential for therapeutic utility, reducing cell loss to apoptosis in injured neurological tissue, as demonstrated in this in vitro model. A clear Raman spectroscopic signal was observed after apparent optimal irradiation, potentially integrable into therapeutic light delivery apparatus for real-time dose metering.