Translational neurosurgery

The aim of the research program is to combat traumatic brain injury (TBI), which is a predominant global public health issue. The strategy is to firstly study TBI in animal models to gain new insights into the mechanisms underlying the development of brain injury following TBI and then transfer this knowledge to new treatment methods in neurointensive care. Additionally, the aim is to test hypotheses generated from clinical research in various animal models. The program is an important part of the Centre of Excellence Neurotrauma at the Uppsala University Hospital.

Project description

Neurosurgery has had a well-established facility for animal studies of TBI since 1986. To simulate the complex patho­biology of human TBI (including contusions, epidural, subdural, and sub­arachnoid hemorrhages, diffuse axonal injury, and mixed forms of injury), a battery of experimental models for different types of injuries is needed. We have established several models for focal contusion injury (such as Controlled Cortical Contusion and Controlled Cortical Impact), a mixed injury model (Lateral Fluid Percussion Injury), and a model for diffuse axonal injury (Central Fluid Percussion Injury). These models are extensively used inter­nationally, facilitating comparisons of results among different research groups. We also have a model for intra­cranial pressure elevation simulating an expansive epidural hematoma, which is highly relevant for studies of intra­cranial dynamics in humans. This model holds significant value for trans­lational research, such as evaluating new methods for monitoring brain injury and the physiology of neuro­intensive care patients.

For functional studies, we have a well-established battery of methods for evaluating the outcomes of brain injury. These methods include the Morris Water Maze, Rotarod, and Concentric Square Field Method. Functional evaluation after TBI has recently been increasingly recognized for its importance in assessing new treatment attempts.

Examples of studies:

  • Studies of secondary injury mechanisms after TBI focusing on neuro­inflammation and traumatic axonal injury.
  • Investigations of neuro­protective drug candidates that block key secondary injury mechanisms after TBI.
  • Research on protein biomarkers for critical secondary injury mechanisms after TBI that can be trans­ferred for use in neuro­intensive care.
  • Studies of brain energy metabolism, blood flow regulation, and oxygen supply.
  • The role of genetics in outcome after brain injury through animal models with transgenic mice and in vitro studies with animal- and patient-specific stem cells.

Project leader: Anders Lewén
Co-investigators: Fredrik Clausen, Elham Rostami, Lars Hillered

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