The perfect solution for everyday patient diagnostics and clinical research at the Institute of Neuropathology in the Charité hospital in Berlin

Dr. Frank Heppner
Director at the Institute of Neuropathology
Charité – Universitätsmedizin Berlin
Dr. Frank Heppner has headed the Institute of Neuropathology at the Charité hospital in Berlin since 2007. With around 55 members of staff, it is the largest neuropathological institute in Germany and examines approximately 17,000 patient samples every year. The affiliated medical research department focuses on neuromuscular research, autoimmune diseases, neuro-oncology, brain tumors and lymphomas, childhood brain tumors and neurodegenerative diseases.
Since spring 2020, the institute has also conducted research on the effects of SARS-CoV-2 infection in the central nervous system (CNS). The first results of investigations into the pathway through which the virus can enter the brain were published in the Nature Neuroscience journal [1] in November.

As Dr. Heppner tells KEYENCE in an interview, if he had to design a fluorescence microscope for his institute, it would have all the features that the BZ fluorescence microscope offers. Whether it’s a quick view of the overall image or a detailed zoom into the individual cell, stitching or optical sectioning, simple operation or portability, the BZ fluorescence microscope has it all covered. So it’s practically tailor-made for him, effortlessly meeting the various requirements of neuropathological research and diagnostics.

Figure 1 Dr. Frank Heppner in the microscopy consultation room with the BZ fluorescence microscope

Since research and patient care are spread over two buildings, the microscopy consultation room in routine diagnostics was chosen as the location for the microscope. With its integrated darkroom, the BZ fluorescence microscope can be set up in any location that offers high efficiency when conducting experiments. The microscopy consultation room is accessible to all staff at all times and features an impressive array of technology, including a network-compatible institute computer and a presentation monitor. The BZ fluorescence microscope connects to this hardware, allowing the fluorescence images to be used immediately for consultation and diagnostics as well as for light microscopic specimens. The fluorescence microscope was an instant success and the first images have already been incorporated into new manuscripts, Dr. Heppner tells us. He says it’s because the BZ is so easy to use: even inexperienced users can quickly generate meaningful, high-quality images.

Figure 2 Colocalization of SARS-CoV spike protein in the olfactory mucosa of individuals with COVID-19

Multiplex fluorescence has mainly been used in research at the Institute of Neuropathology, but it is now being used more and more in diagnostics. Colocalization of target structures in different cell types, especially as part of the research currently being conducted by Dr. Heppner’s research groups on COVID-19, offers an insight into how SARS-CoV-2 can spread from the olfactory mucosa to the brain. The translational results obtained by the Institute of Neuropathology and by more than 20 other participating research groups were published in Nature Neuroscience [1] at the end of November 2020. Epifluorescence microscopy was used to detect the spike protein of SARS-CoV-2 on neurons located in the olfactory mucosa, and the virus can be traced along the olfactory nerve into the brainstem. Multiplex fluorescence shows that the virus – at least so far – cannot be detected in neurons, suggesting that it can also enter the brain through the small blood vessels that run through the CNS.
However, even though the virus has not yet been detected in the brain, some COVID-19 patients exhibit late post-viral neurological problems even after acute symptoms have disappeared (known as long COVID). These are probably due to the reaction of the immune system to SARS-CoV-2, for example in terms of the cytokine storm of immune cells triggered in the brain. Research on long COVID is still in its infancy, and the CNS has an important role to play in these studies.

Figure 3 Image of microglia

Multiple sclerosis is a chronic inflammatory neurological autoimmune disease. Dr. Helena Radbruch’s research group at the Institute of Neuropathology is studying survival niches of certain immune cells in the brains of patients with this disease. The techniques used include sequential staining in the same section and spatially resolved transcriptome analyses. Both are very time-consuming and costly analyses, and the BZ fluorescence microscope has proved to be an efficient, resource-saving way to establish new stains for these techniques. Rapid imaging and sectioning make it easy to test in advance whether tissue samples are suitable for further analysis, and each antibody for individual brain structures such as glial cells, neurons, vessels, meninges, and various immune cell subtypes can be independently validated.
Over the last few years, Dr. Heppner has built up a biobank of autoptic brain material for Alzheimer’s research. The samples from this database usually show high autofluorescence caused by the degenerative deposits in the brain. This problem is part of everyday life for the research group, because Alzheimer’s sufferers often die at an advanced age. In the course of a lifetime, and especially in patients with degenerative brain diseases, many substances can be deposited that cause high autofluorescence. In these cases in particular, Dr. Heppner’s team is grateful that the BZ fluorescence microscope can remove fluorescence blurring in order to produce a clear view of individual cellular structures such as the autophagy apparatus or lysosomes.