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Dynamics of GABA Receptor composition in the recovery phase of stroke – Effect of anti-inflammatory treatment with AMD3100

Michalettos, Georgios (2020) MOBN02 20192
Degree Projects in Molecular Biology
Popular Abstract
GABAergic Neurotrasmission – A “cross-talker” between inflammation and neural plasticity in stroke

Stroke is a leading cause of disability and no pharmacological treatment is currently available to promote recovery in suffering patients. A major part of research is focusing on finding new biological targets which can be pharmacologically intervened with, providing favorable results in facilitating recover of motor functions. Stroke is characterized by a complex pathophysiology involving numerous biochemical, cellular and inflammatory processes. All these processes are interrelated to each other, making it difficult to assess which one is the most responsible for the progression of the overall damage of the neurons. It is crucial,... (More)
GABAergic Neurotrasmission – A “cross-talker” between inflammation and neural plasticity in stroke

Stroke is a leading cause of disability and no pharmacological treatment is currently available to promote recovery in suffering patients. A major part of research is focusing on finding new biological targets which can be pharmacologically intervened with, providing favorable results in facilitating recover of motor functions. Stroke is characterized by a complex pathophysiology involving numerous biochemical, cellular and inflammatory processes. All these processes are interrelated to each other, making it difficult to assess which one is the most responsible for the progression of the overall damage of the neurons. It is crucial, therefore, to find ways to enhance the repair mechanisms of the brain after the acute phase of damage has passed.

γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter, responsible for keeping low levels of brain activity. Extensive studies, however, are starting to reveal that GABA does not only regulate neuronal activity, but it is involved in controlling inflammatory processes as well. These findings are starting to make the GABAergic neurotransmitter system a promising field where one can interfere in order to enhance to plasticity of the brain into restoring its initial functions in parts which they were damaged by stroke.

A promising anti-inflammatory treatment which has been shown to improve recovery in experimental models of stroke is AMD3100, an antagonist to the CXCR4 receptor. This receptor is involved in mediating chemokine responses, molecules that are part of the inflammatory response. Our aim was to determine how AMD3100 can affect the expression of several genes consisting the GABAergic system.

AMD3100 interacts with the GABA system during stroke recovery
There is a strong hypothesis that one of the main problems that do not let the brain manifest its repair capabilities to their maximum during the recovery phase of stroke is the excitatory-inhibitory imbalance present between the hemispheres. In specific, the lesioned hemisphere tends to be over-inhibited, while the unlesioned hemisphere directs the activity of the brain. Using protein and DNA analysis techniques, we observed increased activation of the GABAergic system in the corpus callosum, the part which connects the two hemispheres. In addition, decreased activation of the GABAergic system was confirmed in the unlesioned hemisphere. AMD3100 seemed to be able to restore these imbalances back to physiological levels.

Such results further indicate that AMD3100 might be an efficient treatment for stroke, while on the same time a new perspective gradually arises to overcome the traditional view on neuronal plasticity and inflammation as isolated processes in the post-ischemic brain. In addition, biological elements in the GABAergic system may be ideal for pharmacological targeting.



Master’s Degree Project in Molecular Biology 45 credits 2020
Department of Biology, Lund University

Advisor: Karsten Ruscher
Faculty of Medicine, Department of Clinical Sciences, Laboratory for Experimental Brain Research (Less)
Please use this url to cite or link to this publication:
author
Michalettos, Georgios
supervisor
organization
course
MOBN02 20192
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9028981
date added to LUP
2020-09-11 13:53:11
date last changed
2020-09-11 13:53:11
@misc{9028981,
  author       = {{Michalettos, Georgios}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Dynamics of GABA Receptor composition in the recovery phase of stroke – Effect of anti-inflammatory treatment with AMD3100}},
  year         = {{2020}},
}