PhD Scientific Days 2024

Poster Session H - Theoretical and Translational Medicine 1.

Working Toward the Development of a Feasible Neurovascular Uncoupling Model in Rats

Előadó neve

Mr. Varga, Bence Tamás

Neptun code

NW8V1U

Előadó munkahelye

Semmelweis University, Department of Pharmacology and Pharmacotherapy,

Előadó telefonszáma

0612104416

Előadó e-mail címe

varga.bence@phd.semmelweis.hu

Az előadás címe

Working Toward the Development of a Feasible Neurovascular Uncoupling Model in Rats

Szerző(k) neve és munkahelye

Bence Tamás Varga¹

1: Semmelweis Egyetem Farmakológiai és Farmakoterápiás Intézet

Bemutatás módja

Poszter

Szekció

Poster Session H - Theoretical and Translational Medicine 1.

Language of the presentation

Hungarian

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Our goal was to develop a pharmacologically induced model of neurovascular uncoupling (NVU) in rats, aiming for a translationally valid representation of cognitive decline. A pharmacologically induced NVU model with resulting neurological and cognitive impairments has been documented in mice (Tarantini, 2015). However, such a procedure had not yet been reported in rats.
In our previous study (E1), we used 28 male Hannover Wistar rats. NVU was induced by IP of a pharmacological “cocktail” consisting of N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH, 5 mg/kg), L-NG-nitroarginine methyl ester (L-NAME, 10 mg/kg) and indomethacin (1 mg/kg) and injected twice daily for 8 consecutive days. In a follow-up experiment (E2) with 17 rats, we repeated the same protocol, using halved doses.
In E1, animals were tested in Morris water-maze and fear-conditioning assays, whereas in E2, they performed in novel object recognition, lever-press and spontaneous alternation tasks. Blood pressure (BP) was monitored by tail-cuffs. NVC was measured in the barrel cortex in a non-recovery operation. A laser Doppler probe was used to detect changes in cerebral blood-flow (CBF), while the contralateral whisker pad was stimulated. Brain and small intestine tissue samples were collected postmortem. Samples from E1 were processed for prostaglandin E2 (PGE2) level determination, while measurement of brain EET levels were determined for E2.
Animals treated with the “cocktail” showed no impairment in their performance in any of the cognitive tasks. However, in E1, they showed ~50 % less increase in CBF and an overall increase in systolic BP (12 Hgmm). Intestinal bleeding and ulcers were found in some of them, and ELISA assays revealed significantly decreased levels of PGE2 in the brain (-70%) and small intestine (-86%). In E2, we did not observe significant changes in BP, intestinal autopsy, CBF or EET levels.
We could evoke NVU by the applied mixture of pharmacons in E1, but the treatment also induced hypertension and intestinal alterations. By halving the doses, we could avoid these side effects but also lost efficacy. Thus, refinements are needed to develop an applicable model with regard to finding the ideal dosing regime and learning assays. Another set of measurements were carried out(E3) with old experienced Long Evans rats. The results are currently under evaluation.

University

Semmelweis University

Supervisor

Dr. István Gyertyán

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6818

Start

14:55

End

14:58