Workspace

Brain Protection

In the Brain Protection workspace we will identify mechanisms that protect Neurocognitive circuits’ physiology from extracerebral organ dysfunction, metabolic dysregulation, or iatrogenic adverse events. We aim to understand the mechanisms that impair memory and spatial navigation circuits after surgery and chemotherapy and to determine the influence of preclinical tau and amyloid plaques as vulnerability factors. Furthermore, we will uncover the role of hippocampal vascularization, exercise-induced perfusion and volume as reserve factors.

HOW ORGAN DYSFUNCTION CAN IMPAIR COGNITION

UNDERSTANDING VULNERABILITY

This workspace will focus on post-operative and chemotherapy-induced impairments in memory and spatial navigation and will consider the increased vulnerability of Neurocognitive Circuits due to preclinical tau and amyloid pathology. A central hypothesis is that an excitation/inhibition imbalance as well as activation of the bodily stress response pathway (corticotropin releasing hormone mediated) converge to cause hippocampal network dysfunction. In addition, there is a further broad range of detrimental mechanisms, like changes in extracellular proteolysis and perineuronal nets, synapse loss, damage caused by anaesthetics, vascular dysfunction, impaired “waste” clearance and neuroinflammation. The work programme will be cross-species and multi-scale and we will incorporate a public health perspective.
In summary, this workspace will (i) uncover mechanisms of dysfunction and vulnerability of Neurocognitive Circuits due to surgery and chemotherapy (ii) identify reserve mechanisms and provide evidence for their role in prevention (iii) initiate two proof-of-concept trials for post-operative cognitive dysfunction.

Loss of mental capacity after surgical interventions, such as a hip replacement, can be life altering. But it can be biologically and medically understood at the level of brain circuits. With this understanding, we want to develop therapies that will make surgical interventions safer for our brains in the future.

Prof. Dr. Emrah Düzel

Postoperative Cognitive Dysfunction (POCD)

Postoperative Cognitive Dysfunction (POCD) describes a potential decline of cognitive performance after surgery under anesthesia, which can affect episodic memory as well as learning and concentration performance. Postoperative cognitive dysfunction is a serious health problem in the elderly. Based on demographic changes, as a result of which the population structure has changed significantly in recent decades and will continue to change in th...

Synaptic Failure in Postoperative Cognitive Dysfunction

Postoperative cognitive dysfunction (POCD) is a serious health issue. A vast body of literature exists in the clinical aspects of this condition. In stark contrast, little amyloid load in conjunction with the bodily stress response following surgery and activation of CRF-expressing projection neurons from the hypothalamus destabilize spines - mainly in the hippocampus - probably by severing the F-actin cytoskeleton and depletion of the synapti...

The role of beta-2-microglobulin (B2M) in chemotherapy-induced cognitive dysfunction

Cognitive impairment is a common side effect of chemotherapy, affecting up to 75% of treated cancer patients. Symptoms include decreased short-term memory, word-finding problems, limited attention span and difficulty with concentration and multitasking. While most patients' symptoms improve within a year, 10-20% experience long-term effects. Despite its social and economic importance, this phenomenon has not received enough attention for a lon...

Our
Workspaces

The overarching goal of our research cluster is to understand, treat and prevent cognitive impairment. Hence, we designed four strategically and thematically related workspaces which together cover manifold aspects of cognitive vitality.

Our workspaces stand for innovative collaboration structures on the principles of neurocognitive circuit research and convergence. Within we bring together the fields of cognitive neuroscience, clinical medicine, and engineering/informatics which leads to research on fundamental mechanisms and their translation into clinical applications and technology.