gms | German Medical Science

60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

26. - 28.08.2015, Berlin

The expression of ALDH1 and Aquaporin-4 in reactive astrocytes after traumatic brain injury. An autopsy study

Meeting Abstract

  • corresponding author presenting/speaker Claire Delbridge - Institut für Pathologie der TU München, Neuropathologie, München, Germany
  • Andreas Büttner - Institut für Rechtsmedizin des Universitätsklinikums Rostock, Rostock, Germany
  • Jutta Schöpfer - Institut für Rechtsmedizin der LMU München, München, Germany
  • Matthias Graw - Institut für Rechtsmedizin der LMU München, München, Germany
  • Svetlana Sirko - Institut für Physiologie der LMU, Physiologische Genomik, München, Germany
  • Magdalena Götz - Institut für Physiologie der LMU, Physiologische Genomik, München, Germany
  • Jürgen Schlegel - Institut für Pathologie der TU München, Neuropathologie, München, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP33

doi: 10.3205/15dgnn57, urn:nbn:de:0183-15dgnn578

Published: August 25, 2015

© 2015 Delbridge et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Traumatic brain injury (TBI) is one of the main causes of death worldwide and therapy options are still scarce. Recent works demonstrate that upon TBI a subset of murine reactive astrocytes preferentially resume cell division at juxtavascular position in vivo [1] and acquire stem cell potential in vitro [2]. These findings indicate endogenous stemcell capacity close to a traumatic lesion and raise the interesting question of a possible modulation, leading towards improvement of brain injury outcome.

In order to compare these results with human tissue response, and to further investigate the properties of these reactive juxtavascular astrocytes, we analysed their expression pattern of aldehyde dehydrogenase 1 (ALDH1) and the subtypes ALDH1A1 and ALDH1A3, as well as Aquaporin-4 (AQP4).

ALDH isoforms are expressed in the majority of human cells and are involved in oxidative stress response and cell differentiation. ALDH1A1 and ALDH1A3 are described to have a functional role in the expansion and differentiation of neural stem cells.

AQP4 functions as a water channel and is expressed by perivascular astrocytes, influencing the post traumatic brain edema.

Formalin-fixed and paraffin-embedded samples of brain tissue were collected at the institutes of forensic medicine in Munich and Rostock from 24 deceased (age range 2 yrs to 93 yrs) with TBI between <24 hours to 140 days ante mortem. Immunohistochemistry and immunofluorescence imaging were performed using standard protocols and antibodies directed against GFAP, Ki-67, AQP4, ALDH1 and subtypes ALDH1A1 and ALDH1A3.

A hypertrophy of the juxtavascular astrocytes could be observed 24 h after TBI. The expression of ALDH1 and AQP4 showed a parallel progression with an increase during the first days post TBI, reaching a maximum around the 5.-9. day post trauma. After 14 days the expression decreases. The highest frequency of ALDH1- and AQP4-positve astrocytes was observed in a linear formation along the cortical border of the grey- and white matter.

Thus, a subtype of astrocytes in juxtavascular position is characterised by particular response to TBI. The intermediary position of these cells and their ability to react suggest a critical role in the regulation of post-traumatic tissue response.

Further knowledge of the underlying mechanisms could lead to an improvement of TBI therapy in the future.


References

1.
Bardehle S, Krüger M, Buggenthin F, Schwausch J, Ninkovic J, Clevers H, Snippert HJ, Theis FJ, Meyer-Luehmann M, Bechmann I, Dimou L, Götz M. Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation. Nat Neurosci. 2013 May;16(5):580-6. DOI: 10.1038/nn.3371 External link
2.
Sirko S, Behrendt G, Johansson PA, Tripathi P, Costa M, Bek S, Heinrich C, Tiedt S, Colak D, Dichgans M, Fischer IR, Plesnila N, Staufenbiel M, Haass C, Snapyan M, Saghatelyan A, Tsai LH, Fischer A, Grobe K, Dimou L, Götz M. Reactive glia in the injured brain acquire stem cell properties in response to sonic hedgehog. Cell Stem Cell. 2013 Apr 4;12(4):426-39. DOI: 10.1016/j.stem.2013.01.019 External link