Advanced theranostic nanocarrier-mediated delivery of NGF in a combination therapy trigger enhanced recovery after stroke

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Wacker M, Wetterling F, Feczko T, Arkelius K, Arnou A, Lellouche J, Ansar S, Advanced theranostic nanocarrier-mediated delivery of NGF in a combination therapy trigger enhanced recovery after stroke, Journal of Cerebral Blood Flow & Metabolism, BRAIN and BRAIN-PET 2022, Glasgow, Scotland, 28 May - 1 June 2022, 42, 1S, 2022, 263 - 264Download Item:
Abstract:
Background: The majority of people who survive the
acute phase of stroke remain permanently disabled. So
far, no treatment to improve function exist, nerve
growth factor (NGF) has emerged as excellent candidate
to boost recovery processes. However, the approach to
effective deliver NGF has not been possible since it does
not pass the blood brain barrier.
Aim: To evaluate if use of an advanced theranostic nano-
carrier-mediated delivery of NGF to after stroke enhance
recovery of the brain by inducing endogenous repair
mechanisms such as neurogenesis and angiogenesis.
Method: Transient middle cerebral artery occlusion was
induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered i.p at 6 and 24 hours and the NGF was given i.v at
day 3 post-reperfusion. Neurological functions were
assessed up to 4 weeks after stroke and 9.4 T magnetic
resonance imaging was used to monitor perfusion and
morphological changes. Recovery processes such as neurogenesis and angiogenesis were evaluated at 4 weeks
post stroke by Western Blot.
Results: The combination therapy with NGF and U0126
significantly improved neurological function, perfusion and
recovery processes compared to vehicle and U0126 treat-
ment alone. An enhanced NGF protein levels and activa-
tion of the TRKa/b signaling pathway in addition to
enhanced neurogenesis were observed.
Conclusion: NGF delivered by advanced theranostic
nanocarrier promotes recovery processes after stroke
and most importantly our delivery approach has demonstrated to be successful. This will be the first step that will
lead to novel treatment strategies for neurological disorders.
Author's Homepage:
http://people.tcd.ie/wetterf
Author: Wetterling, Friedrich
Other Titles:
Journal of Cerebral Blood Flow & MetabolismBRAIN and BRAIN-PET 2022
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42;1S;
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