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3. An analysis of the CatWalk XT and a composite score to assess neurofunctional deficits after photothrombosis in mice

Author

Baermann, J., Walter, H. L., Pikhovych, A., Endepols, H., Fink, G. R., Rueger, M. A., Schroeter, M., Baermann, J., Walter, H. L., Pikhovych, A., Endepols, H., Fink, G. R., Rueger, M. A., and Schroeter, M.

Abstract

The purpose of this study was to evaluate CatWalk's capability for assessing the functional outcome after photothrombotic stroke affecting the motor cortex of mice. Mice were tested up to 21 days after photothrombosis or sham surgery using CatWalk, and a composite score assessing functional deficits (neuroscore). The neuroscore demonstrated deficits of the contralateral forelimb for more than two weeks after stroke. There were no asymmetric or coordinative dysfunctions of limbs detected by CatWalk. However, CatWalk data revealed impairment of locomotion speed and its depending parameters for one-week after stroke in strong correlation to the neuroscore. Data suggest that the composite neuroscore allows to more sensitively and precisely specify and quantify photothrombosis-induced hemisyndromes than CatWalk.

Published
2021

4. An analysis of the CatWalk XT and a composite score to assess neurofunctional deficits after photothrombosis in mice

Author

Baermann, J., Walter, H. L., Pikhovych, A., Endepols, H., Fink, G. R., Rueger, M. A., Schroeter, M., Baermann, J., Walter, H. L., Pikhovych, A., Endepols, H., Fink, G. R., Rueger, M. A., and Schroeter, M.

Abstract

The purpose of this study was to evaluate CatWalk's capability for assessing the functional outcome after photothrombotic stroke affecting the motor cortex of mice. Mice were tested up to 21 days after photothrombosis or sham surgery using CatWalk, and a composite score assessing functional deficits (neuroscore). The neuroscore demonstrated deficits of the contralateral forelimb for more than two weeks after stroke. There were no asymmetric or coordinative dysfunctions of limbs detected by CatWalk. However, CatWalk data revealed impairment of locomotion speed and its depending parameters for one-week after stroke in strong correlation to the neuroscore. Data suggest that the composite neuroscore allows to more sensitively and precisely specify and quantify photothrombosis-induced hemisyndromes than CatWalk.

Published
2021

5. Engineered antibodies: new possibilities for brain PET?

Author

Sehlin, D, Syvanen, S, Ballanger, B, Barthel, H, Bischof, GN, Boche, D, Boecker, H, Bohn, KP, Borghammer, P, Cross, D, Di Monte, D, Drzezga, A, Endepols, H, Giehl, K, Goedert, M, Hammes, J, Hansson, O, Herholz, K, Hoeglinger, G, Hoenig, M, Jessen, F, Klockgether, T, Lafaye, P, Lammerstma, A, Mandelkow, E, Mandelkow, E-M, Maurer, A, Mollenhauer, B, Neumaier, B, Nordberg, A, Onur, O, Reetz, K, Rodriguez-Vietez, E, Rominger, A, Rowe, J, Sabri, O, Schneider, A, Strafella, A, van Eimeren, T, Vasdev, N, Villemagne, V, Willbold, D, Sehlin, D, Syvanen, S, Ballanger, B, Barthel, H, Bischof, GN, Boche, D, Boecker, H, Bohn, KP, Borghammer, P, Cross, D, Di Monte, D, Drzezga, A, Endepols, H, Giehl, K, Goedert, M, Hammes, J, Hansson, O, Herholz, K, Hoeglinger, G, Hoenig, M, Jessen, F, Klockgether, T, Lafaye, P, Lammerstma, A, Mandelkow, E, Mandelkow, E-M, Maurer, A, Mollenhauer, B, Neumaier, B, Nordberg, A, Onur, O, Reetz, K, Rodriguez-Vietez, E, Rominger, A, Rowe, J, Sabri, O, Schneider, A, Strafella, A, van Eimeren, T, Vasdev, N, Villemagne, V, and Willbold, D

Abstract

Almost 50 million people worldwide are affected by Alzheimer's disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, non-invasive positron emission tomography (PET) biomarkers for early diagnosis, monitoring of disease progression, and assessment of therapeutic effects. Traditionally, PET ligands have been based on small molecules that, with the right properties, can penetrate the blood-brain barrier (BBB) and visualize targets in the brain. Recently a new class of PET ligands based on antibodies have emerged, mainly in applications related to cancer. While antibodies have advantages such as high specificity and affinity, their passage across the BBB is limited. Thus, to be used as brain PET ligands, antibodies need to be modified for active transport into the brain. Here, we review the development of radioligands based on antibodies for visualization of intrabrain targets. We focus on antibodies modified into a bispecific format, with the capacity to undergo transferrin receptor 1 (TfR1)-mediated transcytosis to enter the brain and access pathological proteins, e.g. amyloid-beta. A number of such antibody ligands have been developed, displaying differences in brain uptake, pharmacokinetics, and ability to bind and visualize the target in the brain of transgenic mice. Potential pathological changes related to neurodegeneration, e.g. misfolded proteins and neuroinflammation, are suggested as future targets for this novel type of radioligand. Challenges are also discussed, such as the temporal match of radionuclide half-life with the ligand's pharmacokinetic profile and translation to human use. In conclusion, brain PET imaging using bispecific antibodies, modified for receptor-mediated transcytosis across the BBB, is a promising method for specifically visualizing molecules in the brain that are difficult to target with traditional small molecule ligands.

Published
2019

11. Glutamate carboxypeptidase II expression-dependent microPET visualization of reendothelialization after balloon denudation in a rat model: a novel tool for non-invasive in vivo molecular imaging

Author

Cornelissen, A., Zlatopolskiy, B., Simsekyilmaz, S., Endepols, H., Brucerius, J., Winz, O., Neumaier, A., Morgenroth, A., Marx, N., Mottaghy, F., Vogt, F., Cornelissen, A., Zlatopolskiy, B., Simsekyilmaz, S., Endepols, H., Brucerius, J., Winz, O., Neumaier, A., Morgenroth, A., Marx, N., Mottaghy, F., and Vogt, F.

Published
2017

12. Glutamate carboxypeptidase II expression-dependent microPET visualization of reendothelialization after balloon denudation in a rat model: a novel tool for non-invasive in vivo molecular imaging

Author

Cornelissen, A., Zlatopolskiy, B., Simsekyilmaz, S., Endepols, H., Brucerius, J., Winz, O., Neumaier, A., Morgenroth, A., Marx, N., Mottaghy, F., Vogt, F., Cornelissen, A., Zlatopolskiy, B., Simsekyilmaz, S., Endepols, H., Brucerius, J., Winz, O., Neumaier, A., Morgenroth, A., Marx, N., Mottaghy, F., and Vogt, F.

Published
2017

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