Effects of Nerinetide on Behavioural Recovery of Experimental Stroke in the Rat

You can have your competent? doctor summarize the 323 pages and provide you with the tidbits that will get you recovered.

Your competent? doctor did do something with nerinetide a long time ago, RIGHT?

Do you prefer your doctor incompetence NOT KNOWING OR NOT DOING?

nerinetide (7 posts to February 2020)

 Effects of Nerinetide on Behavioural Recovery of Experimental Stroke in the Rat

by

Beatrice Ballarin

A thesis submitted in conformity with the requirements

for the degree of Doctor of Philosophy

Institute of Medical Science

University of Toronto

Abstract

Stroke is the leading cause of long-term disability in Canada and a significant financial burden on

the healthcare system, yet no pharmaceutical intervention is available that has been proven to

improve recovery. N-methyl-D- aspartate receptors (NMDARs) are known to play a substantive

role in neural circuit rebuilding post-injury. Studies from acute stroke research suggested that

interfering with the toxic GluN2B-subunit of NMDAR downstream signalling or enhancing the

pro-survival GluN2A-subunit one is beneficial in promoting neuroprotection. Nerinetide has been

shown to promote neuroprotection during acute ischemia, by interfering with nitric oxide (NO)

production and the pro-death signalling cascade mediated by the GluN2B-subunit of the

NMDARs. The purpose of this dissertation was to evaluate the role of nerinetide in promoting

functional recovery and molecular changes when administered during the recovery phase after

stroke. In this thesis, the effect of nerinetide in promoting functional recovery was tested in two

different stroke models in rats. Results show that nerinetide promoted functional recovery only

after cortical motor injury and was correlated with the upregulation of selected key pro-survival

proteins (GluN2A, PSD-95, PI3K, AKT, ERK1/2, CREB, and S6). In particular, CREB has been

found phosphorylated at 6 and 24 hours following the first dose of nerinetide in the cortical peri-

infarct region and it is believed to play a key role in promoting functional recovery. 

This thesis has contributed to the field of stroke research by applying nerinetide for the first time

in a recovery setting and by highlighting a set of protein candidates that may have contributed to

these recovery mechanisms. Future studies should investigate the role of CREB in connection with

recovery mechanisms post-stroke and enhancement by the application of specific

pharmacotherapies.