Monitoring the Neuroinflammatory Response Following Acute Brain Injury

Abstract

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are major contributors to morbidity and mortality. Following the initial insult, patients may deteriorate due to secondary brain damage. The underlying molecular and cellular cascades incorporate components of the innate immune system. There are different approaches to assess and monitor cerebral inflammation in the neuro intensive care unit. The aim of this narrative review is to describe techniques to monitor inflammatory activity in patients with TBI and SAH in the acute setting. The analysis of pro- and anti-inflammatory cytokines in compartments of the central nervous system (CNS), including the cerebrospinal fluid and the extracellular fluid, represent the most common approaches to monitor surrogate markers of cerebral inflammatory activity. Each of these compartments has a distinct biology that reflects local processes and the cross-talk between systemic and CNS inflammation. Cytokines have been correlated to outcomes as well as ongoing, secondary injury progression. Alongside the dynamic, focal assay of humoral mediators, imaging, through positron emission tomography, can provide a global in vivo measurement of inflammatory cell activity, which reveals long-lasting processes following the initial injury. Compared to the innate immune system activated acutely after brain injury, the adaptive immune system is likely to play a greater role in the chronic phase as evidenced by T-cell-mediated autoreactivity toward brain-specific proteins. The most difficult aspect of assessing neuroinflammation is to determine whether the processes monitored are harmful or beneficial to the brain as accumulating data indicate a dual role for these inflammatory cascades following injury. In summary, the inflammatory component of the complex injury cascade following brain injury may be monitored using different modalities. Using a multimodal monitoring approach can potentially aid in the development of therapeutics targeting different aspects of the inflammatory cascade and improve the outcome following TBI and SAH.

Expression profiling suggests microglial impairment in human immunodeficiency virus neuropathogenesis

“…Proinflammatory cytokines TNFa, IL-1b, and IL-6, as well as increased reactive oxygen species (ROS) and reactive nitrogen species, can be injurious to healthy cells and are commonly seen in brain or cerebrospinal fluid of individuals suffering CNS disease, including HIVE. [27][28][29] In our study, both HIV groups demonstrated altered transcripts related to immune activation including the proinflammatory cytokines IL-1b and IL-6, and the major TNFa receptor Tnfrsf1a. Increased transcription of IL-6 and Tnfrsf1a supports our earlier immunohistochemical findings within the same subjects that show substantial widespread microglial activation in HIV, including individuals on cART prior to death and without detectable virus in brain.…”

“…Pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, as well as increased reactive oxygen species (ROS) and reactive nitrogen species (RNS), can be injurious to healthy cells and are commonly seen in brain or CSF of individuals suffering CNS disease, including HIVE 27–29 . In our study, both HIV groups demonstrated altered transcripts related to immune activation including the pro-inflammatory cytokines, IL-1β and IL-6 , and the major TNFα receptor, Tnfrsf1a .…”

Modelling human pathology of traumatic brain injury in animal models

“…MBL; mannose-binding lectin, MASP; mannose-associated serine protease, MMP-9; Matrix MetalloProteinase 9. Adopted from Thelin et al [62].…”

How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury

“…If 'inflammation' is considered as the endogenous response to injury, it has to cover a wide spectrum of both humoral and cellular events that span both innate and adaptive immunity. 46 Access to a number of biological compartments (plasma, CSF, brain extracellular fluid) has allowed researchers to measure a range of inflammatory biomarkers following TBI but each of these biocompartments has its limitations with respect to interpretation. For example, plasma sampling is confounded by extracranial trauma; CSF sampling is usually intermittent and the CSF compartment may reflect a sump for clearance of inflammatory substances; 47,48 and microdialysate sampling from the brain extracellular space is limited by the proportion of a soluble mediator that crosses into the microdialysis catheter which varies with molecular weight, charge and methodological variations in microdialysis technique.…”