Traumatic brain injuries

Traumatic brain injury (TBI) is caused when significant force is applied to the head. This may be due to an impact by blunt force, by the penetration of an object, or a rotational acceleration or deceleration of the head. TBI is one of the leading causes of death among young individuals, and the success in management in the clinical setting is dependent on an accurate characterization of the distribution and severity of the brain injuries. Hence a number of biomarkers in serum and liquor have been evaluated, and introduced, to assist in the assessment of injury severity and prognosis, and which serve as important tools for the choice of actions taken to treat the patients. In the postmortem setting, forensic pathologists focus on the detection, distribution and amount of contusions and secondary hemorrhages to assess the injuries. However, in many cases of fatal TBI the bleedings occupy a very small proportion of the total brain volume, and may as such not explain the death, but rather serve as indirect evidence of neuronal, and particularly axonal injuries, which may disrupt vital parts of the brain neurocircuitry. In the early phase, axonal injuries are however very difficult to visualize upon conventional microscopic examination. Our studies will focus on the detection, distribution and amount of axonal injuries to help in the assessment of injury severity. To this end we will use select morphological methods such as light sheet microscopy, fluorescent correlation spectroscopy, stereology and biochemical analyses of tissue homogenates, serum and liquor. We also plan to use proximity ligation assay to identify transient protein interactions occurring at different time windows to estimate the age of the injuries, since this information is important for the police in obscure cases. The studies will include experimental studies on rats with models of both rotational force and blunt force impact as well as postmortem human brain investigations.

PI: Henrik Druid, henrik.druid@ki.se