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Automated behavioral testing system for assessment of neurological function in meningitis

Automated behavioral testing system for assessment of neurological function in meningitis

Streptococcus pneumoniae is a bacterium which colonizes the nose and throat asymptomatically in a significant portion of adults and children. In case of immune system imbalance, the bacteria could become invasive and provoke severe infections. The pneumococcus is the leading cause of bacterial meningitis (inflammation of the meninges, the subarachnoid space and the brain tissue), with case fatality rates of around 30% in high-income countries and up to 51% in low-income countries. Long-term effects of the disease are neurological deficits, behavioral changes, impairment of consciousness and learning disabilities which comprise a high burden to recovered patients and healthcare system.

Our lab studies how the pneumococci interact with the body, cause damage to our brain and how our immune system reacts to them. Recently we have been focusing on factors promoting bacterial growth and damage to the brain, as well as novel therapeutic approaches, such as toxin scavenging. When studying the nervous system, evaluation of its function in disease is crucial for generation of high-quality data and transferring experimental findings to the most complex object – the human brain.

Thanks to the generous funding from the UniBern Forschungsstiftung, we were able to purchase an ANYmaze automated behavioral testing system by Stoelting. The system is comprised of a highly sensitive camera and automated software and allows for unbiased evaluation of behavior of experimental animals, such as spontaneous activity (Figure 1) or performance in a wide palette of neurological tests.

The instrument allows us to reliably and objectively track the clinical course of the disease in an experimental model of bacterial meningitis. We were able to reliably demonstrate the crucial role of specific pneumococcal genes for initiation and persistence of infection, seen as alteration of spontaneous activity of the mice, as seen on Figure 2. Thanks to the UniBern Forschungsstiftung, we will be able to apply a whole array of functional tests in our other projects, increasing the translational value of our results and contributing to animal welfare.

Dr. Nikola Tomov

Institute of Anatomy, University of Bern

Figure 1. Line tracks over 5 minutes of spontaneous activity in an open field. The purple line represents the movement of the middle point of the mouse during the test, and the yellow frame is the outline of the apparatus. Shown is a pronounced diminishing of spontaneous activity after an infection with S. pneumoniae and development of meningitis symptoms.
Figure 2. Typical curve of spontaneous activity in a course of meningitis infection with a wild type (red) and a mutant (blue line) S. pneumoniae strains, showing different clinical courses. Note the constant reduction of activity of the wild-type infected animals, and the relative resolution in the ones infected with the mutant strain.
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