Three Experimental Models for Evaluation of Three Different Mechanisms in Blast TBI
Paper in proceedings, 2011
Traumatic Brain Injuries (TBI) induced by blast waves from detonations provides huge diagnostic problems. It may be assumed that several mechanisms contribute to the injury. Thus, the primary blast overpressure, acceleration movements, focal impacts as well as heating could contribute to the injury. In a number of experiments we have evaluated the injuries induced by these mechanisms. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of PETN explosives that result in a pressure wave with a magnitude between 130 and 600 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The pressure wave is of simple Friedländer type, with a duration of less than 0.5 ms. Animals that are exposed side on suffer from lethal bleedings from the lungs if the peak pressure exceeds 300 kPa. In recent experiments we have mounted animals in a rigid metallic body protection that covers all parts of the body except for the head, which rests on a bar that prevents from acceleration movements. With this protection the animals survive 600 kPa. The second model is a controlled penetration of a 2 mm thick needle, which is assumed to represent the focal impact of fragments. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. This model is assumed to be relevant for rapid acceleration movements that can occur after explosions. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmittors in the hippocampus after both acceleration and penetration injuries. Exposure to primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a down regulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. Detailed studies on the anxiety related pathways from the brainstem represent an important part these continued studies.