Translational Neurosurgery

Goals

The objective of the program is to combat Traumatic Brain Injury (TBI), a major global public health problem. The strategy is to provide translational results in animal models of TBI for exploration in the Neuro-ICU ultimately resulting in novel TBI treatment options. The program is closely related to the Centre of Excellence Neurotrauma (www.neurotrauma.se) at the Uppsala University Hospital.

Methods

The Section of Neurosurgery has an animal modelling facility established in 1986. To simulate the high degree of complexity of human TBI pathobiology (e.g. focal contusions, epidural, subdural and intraparechymal hemorrhages, diffuse axonal injury and mixed forms) a battery of animal models with different mechanical impact properties is required. We have established two focal contusion models of TBI (the Controlled Cortical Contusion Model and the Controlled Cortical Impact Model) and one mixed model (the Lateral Fluid Percussion Injury Model) for rodents. We recently established a diffuse axonal injury model (the Central Fluid Percussion Injury Model) in rat and mouse. The models are widely used internationally facilitating comparison of data between research groups.

We also have a pig model for raised intracranial pressure (ICP) simulating an expansive epidural heamatoma with close resemblance with human intracranial dynamics. The model allows the use of similar monitoring devices as in patients, which is of great benefit in translational research.

A battery of methods for evaluation of the functional outcome of small animals following TBI is well established, including the Morris Water Maze, the Rotarod and the Concentric Square Field Method. Behavioral outcome measures are considered increasingly important in studies of neuroprotective drug effects and other therapeutic interventions.

Main lines of research

Studies on secondary brain injury mechanisms with focus on neuroinflammation and traumatic axonal injury.

Studies on neuroprotective drug candidates to block important secondary injury mechanisms.

Studies on protein biomarkers of secondary injury mechanisms to be translated to TBI patients in neurointensive care.

Studies on cerebral energy metabolism, blood flow and tissue oxygenation.

Significance

The animal modelling platform will provide important novel knowledge on the secondary injury mechanisms following TBI:

-paving the way for individualized TBI treatment and

-identifying new targets for intervention to be translated to the Neuro-ICU setting with the ultimate goal of improving the outcomes for human victims of TBI.

Senior investigators

Anders Lewén, Associate Professor (group leader)
Lars Hillered, Professor emeritus
Fredrik Clausen, Assistant Professor
Per Enblad, Professor

Ph.D. students

Philip Dyhrfort, M.D.