Central nervous system injury–induced immune suppression

Abstract

Central nervous system trauma is a common cause of morbidity and mortality. Additionally, these injuries frequently occur in younger individuals, leading to lifetime expenses for patients and caregivers and the loss of opportunity for society. Despite this prevalence and multiple attempts to design a neuroprotectant, clinical trials for a pharmacological agent for the treatment of traumatic brain injury (TBI) or spinal cord injury (SCI) have provided disappointing results. Improvements in outcome from these disease processes in the past decades have been largely due to improvements in supportive care. Among the many challenges facing patients and caregivers following neurotrauma, posttraumatic nosocomial infection is a significant and potentially reversible risk factor. Multiple animal and clinical studies have provided evidence of posttraumatic systemic immune suppression, and injuries involving the CNS may be even more prone, leading to a higher risk for in-hospital infections following neurotrauma. Patients who have experienced neurotrauma with nosocomial infection have poorer recovery and higher risks of long-term morbidity and in-hospital mortality than patients without infection. As such, the etiology and reversal of postneurotrauma immune suppression is an important topic. There are multiple possible etiologies for these posttraumatic changes including the release of damage-associated molecular patterns, the activation of immunosuppressive myeloid-derived suppressor cells, and sympathetic nervous system activation. Postinjury systemic immunosuppression, particularly following neurotrauma, provides a challenge for clinicians but also an opportunity for improvement in outcome. In this review, the authors sought to outline the evidence of postinjury systemic immune suppression in both animal models and clinical research of TBI, TBI polytrauma, and SCI.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow‐up

“…It may be that even mild CNS injuries can lead to both a weakened immune system, and thus susceptibility to infection, and ADRD-associated neuronal damage accumulation. 49 Further, cognition was measured at only one time point in this study, but studies that investigated HSV and CMV independently showed infected individuals had faster cognitive decline over an extended follow-up time. 18,48 We anticipate addressing this with the completion of Wave 5.5 of the ECA.…”

Identification of TIMP1 as an inflammatory biomarker associated with temporal lobe epilepsy based on integrated bioinformatics and experimental analyses

“…Pitsch et al demonstrated spontaneous recurrent seizures and persisting memory deficits, and the sclerotic hippocampus was populated with CD8 + T-cells escorted by NK-cells [ 33 ]. MDSCs can inhibit other immune cells, including T-, B-, and NK-cells, and are closely related to many nervous system diseases [ 34 , 35 ]. Taken together, differentially expressed IRGs and IRG-related DEGs were likely associated with neuroinflammation and the immune microenvironment.…”

Optimization of Nutrition after Brain Injury: Mechanistic and Therapeutic Considerations

“…Beyond the acute phase, microglia remain phenotypically activated [ 29 ], inducing long-term inflammation that serves as a link between acute illness and chronic neurodegeneration and symptomatic cognitive impairment and dementia [ 30 ]. TBI-induced immunosuppression is not fully understood but is hypothesized to be the result of the downregulation of leukocyte activity in response to DAMP release and inflammasome activation [ 31 ].…”