Cerebral dysfunctions caused by sepsis during aging

November 18, 2021

(picture: Nature Reviews Immunology, Manabe et. al. 2021)

 

A differentiated look at the relationship between sepsis and acute cerebral dysfunction

Sepsis occurs when the body's own immune reactions against an infection inflicts damage to its own organs and tissues.  Such systemic inflammation is a life-threatening condition and one of the most severe complications of infectious diseases. It may be caused by bacteria, viruses, fungi or parasites.

Systemic inflammations caused by Sepsis may induce an acute cerebral dysfunction known as sepsis- associated encephalopathy (SAE). Recent data from intensive care units show, that half of all patients with sepsis also develop SAE. Patients surviving a sepsis show an increased prevalence of sustained cognitive impairments for several years after initial sepsis onset.

Prof. Michael Heneka is Director of the Department of Neurodegenerative Disorders and a member of the Cluster of Excellence ImmunoSensation2 at the University Clinics Bonn. Heneka's and his team's efforts in basic and translational research focus on the field of neurodegeneration and neuroinflammation: Besides Alzeimers disease, amyotrophic lateral sclerosis, and multiple sclerosis, Pro. Henekas research is focssed on septic encephalopathy. Together with young researcher Tatsuya Manabe, Prof. Heneka now published a nuanced review on the relationship between sepsis and acute cerebral dysfunction.

Until today, it is largely unclear why SEA is developed only by some but not all sepsis patients. This also holds true for the factors determining the persistence of SAE. Based on the chronology of pathology and the dynamic changes in cognition upon sepsis onset, Heneka and Manabe dissect the cerebral effects of sepsis. The scientists discuss sepsis associated neuroinflammation, alternations in neuronal synapses as well as neurovascular changes. They also outline potential factors contributing to the development and persistence of SAE in older patients. In focus are both medical issues like sedatives and their side effects, as well as conditions like renal dysfunction or latent virus reactivation.

 

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) was reported to cause viral sepsis in more than half of the hospitalized patients suffering from severe Covid-19, the researchers close their consideration with a linking to COVID-19: Recent data shows that COVID-19 infections can lead to the loss of neuron and neuronal integrity and hence impair brain functioning. The underlying mechanisms remain to be elucidated, but may include encephalitis, vasculopathy or vasculitis, effects of systemic inflammation, induction of autoimmune reactions and peripheral organ dysfunctions. Hence, Heneka and Manabe postulate that some of the mechanisms that underpin neuropathology in SAE may also be relevant to delirium and persisting cognitive impairments that are seen in patients with severe COVID-19.

 

Tatsuya Manabe has joined the Heneka lab as a PhD student in 2017. He has been fascinated with the significant roles of the innate immunity in neurodegenerative diseases such as Alzheimer’s disease. His current interest focuses on the microglia-synapse interactions and innate immune memory in particular after the systemic inflammation, on the basis of which he has been working for the sepsis-associated encephalopathy project.

 

Publication:

Tatsuya Manabe and Michael T. Heneka: Cerebral dysfunctions caused by sepsis during aging. Nature Reviews Immunology. https://www.nature.com/articles/s41577-021-00643-7

 

Contact:

Prof. Michael T. Heneka

Medical Faculty, University of Bonn
University Hospital of Bonn
Venusberg-Campus 1
53127 Bonn

mail(at)henekalab.com