Publications

Temporal and Spatial Gene Expression Profile of Stroke Recovery Genes in Mice.

Abstract (Expand)

Stroke patients show some degree of spontaneous functional recovery, but this is not sufficient to prevent long-term disability. One promising approach is to characterize the dynamics of stroke recovery … genes in the lesion and distant areas. We induced sensorimotor cortex lesions in adult C57BL/6J mice using photothrombosis and performed qPCR on selected brain areas at 14, 28, and 56 days post-stroke (P14-56). Based on the grid walk and rotating beam test, the mice were classified into two groups. The expression of cAMP pathway genes Adora2a, Pde10a, and Drd2, was higher in poor- compared to well-recovered mice in contralesional primary motor cortex (cl-MOp) at P14&56 and cl-thalamus (cl-TH), but lower in cl-striatum (cl-Str) at P14 and cl-primary somatosensory cortex (cl-SSp) at P28. Plasticity and axonal sprouting genes, Lingo1 and BDNF, were decreased in cl-MOp at P14 and cl-Str at P28 and increased in cl-SSp at P28 and cl-Str at P14, respectively. In the cl-TH, Lingo1 was increased, and BDNF decreased at P14. Atrx, also involved in axonal sprouting, was only increased in poor-recovered mice in cl-MOp at P28. The results underline the gene expression dynamics and spatial variability and challenge existing theories of restricted neural plasticity.

Authors: J. Gotz, F. Wieters, V. J. Fritz, O. Kasgen, A. Kalantari, G. R. Fink, M. Aswendt

Date Published: 9th Feb 2023

Publication Type: Journal

Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Abstract (Expand)

Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after … photothrombotic stroke in mice with attenuated reactive gliosis (GFAP–/–Vim–/–). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP–/–Vim–/– mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes modulate recovery-promoting plasticity responses after ischemic stroke.

Authors: Markus Aswendt, Ulrika Wilhelmsson, Frederique Wieters, Anna Stokowska, Felix Johannes Schmitt, Niklas Pallast, Yolanda de Pablo, Lava Mohammed, Mathias Hoehn, Marcela Pekna, Milos Pekny

Date Published: 1st Feb 2022

Publication Type: Journal

Graph theoretical quantification of white matter reorganization after cortical stroke in mice

Abstract (Expand)

Stroke is a devastating disease leading to cell death and disconnection between neurons both locally and remote, often resulting in severe long-term disability. Spontaneous reorganization of areas and … pathways not primarily affected by ischemia is, however, associated with albeit limited recovery of function. Quantitative mapping of whole-brain changes of structural connectivity concerning the ischemia-induced sensorimotor deficit and recovery thereof would help to target structural plasticity in order to improve rehabilitation. Currently, only in vivo diffusion MRI can extract the structural whole-brain connectome noninvasively. This approach is, however, used primarily in human studies. Here, we applied atlas-based MRI analysis and graph theory to DTI in wild-type mice with cortical stroke lesions. Using a DTI network approach and graph theory, we aimed at gaining insights into the dynamics of the spontaneous reorganization after stroke related to the recovery of function. We found evidence for altered structural integrity of connections of specific brain regions, including the breakdown of connections between brain regions directly affected by stroke as well as long-range rerouting of intra- and transhemispheric connections related to improved sensorimotor behavior.

Authors: Niklas Pallast, Frederique Wieters, Marieke Nill, Gereon R. Fink, Markus Aswendt

Date Published: 1st Aug 2020

Publication Type: Journal

Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity

Abstract

Not specified

Authors: Anna Stokowska, Markus Aswendt, Daniel Zucha, Stephanie Lohmann, Frederique Wieters, Javier Morán Suarez, Alison L. Atkins, YiXian Li, Maria Miteva, Julia Lewin, Dirk Wiedermann, Michael Diedenhofen, Åsa Torinsson Naluai, Pavel Abaffy, Lukas Valihrach, Mikael Kubista, Mathias Hoehn, Milos Pekny, Marcela Pekna

Date Published: 15th May 2023

Publication Type: Journal

How to establish and maintain a multimodal animal research dataset using DataLad

Abstract (Expand)

Sharing of data, processing tools, and workflows require open data hosting services and management tools. Despite FAIR guidelines and the increasing demand from funding agencies and publishers, only a … few animal studies share all experimental data and processing tools. We present a step-by-step protocol to perform version control and remote collaboration for large multimodal datasets. A data management plan was introduced to ensure data security in addition to a homogeneous file and folder structure. Changes to the data were automatically tracked using DataLad and all data was shared on the research data platform GIN. This simple and cost-effective workflow facilitates the adoption of FAIR data logistics and processing workflows by making the raw and processed data available and providing the technical infrastructure to independently reproduce the data processing steps. It enables the community to collect heterogeneously acquired and stored datasets not limited to a specific category of data and serves as a technical infrastructure blueprint with rich potential to improve data handling at other sites and extend to other research areas.

Authors: Aref Kalantari, Michał Szczepanik, Stephan Heunis, Christian Mönch, Michael Hanke, Thomas Wachtler, Markus Aswendt

Date Published: 1st Dec 2023

Publication Type: Journal

Proportional recovery in mice with cortical stroke

Abstract (Expand)

The proportional Recovery Rule (PRR) has been frequently used to predict recovery of lost motor function in acute stroke patients. However, it still needs to be explored whether the same concept applies … to preclinical, i.e. animal models of stroke recovery. To address this question, we investigated behavioral data from 125 adult male C57Bl/6J mice with photothrombotic strokes in the sensorimotor cortex. Lesion size and location were determined in the first week using in vivo T2-weighted MRI. Motor recovery was evaluated repeatedly over four weeks using the cylinder, grid walk, and rotating beam test. Recovery trajectories were analyzed using a newly formulated Mouse Recovery Rule (MRR), comparing it against the traditional PRR. Initial findings indicated variable recovery patterns, which were separated using a stepwise linear regression approach resulting in two clusters: 47% PRR and 53% MRR. No significant correlation was found between recovery patterns and lesion size or location, suggesting that other biological factors drive individual differences in recovery. Of note, in the MRR cluster, animals recovered to 90% of their initial behavioral state within the first four weeks post-stroke, which is higher than the 70% recovery usually reported in human PRR studies. This study demonstrates the complexity of translating the PRR to stroke recovery models in mice and underscores the need for species-specific recovery models. Our findings have implications for designing and interpreting therapeutic strategies for stroke recovery in preclinical settings, with the potential to improve the predictive accuracy of stroke recovery assessments.

Authors: Aref Kalantari, Carolin Hambrock, Christian Grefkes, Gereon R. Fink, Markus Aswendt

Date Published: 12th Oct 2024

Publication Type: Journal

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