Brain Disorders & Therapy

Therapeutic strategies to enhance post stroke recovery of aged brains

Global Summit on Stroke

August 03-05, 2015 Birmingham, UK

Aurel Popa-Wagner

Posters-Accepted Abstracts: Brain Disord Ther

Abstract:

We and others have shown that potential mechanisms for self-repair also operate in the post-ischemic aged brain. Attractive therapeutic
strategies to enhance post stroke recovery of aged brains include both physical methods and methods of cellular therapy that can
enhance the endogenous restorative mechanisms of the injured brain by supporting processes of neovascularization, neurogenesis and
neural reorganization. In the first hours post-stroke H2S-induced hypothermia may be a viable clinical approach to protecting the brain
from cerebral injury long-term hypothermia. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy
in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow
an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived
therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the
stem cell mobilizer Granulocyte-colony Stimulating Factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived predifferentiated
mesenchymal cells (BM MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this
end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs were administered intravenously to Sprague-
Dawley rats at six hour safer transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by MRI at 3 and 48
days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival
period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function
after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration”.
However, G-CSF+BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further
improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative
therapies would have to be carried out for a much longer time.