A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models

F. Mastroiacovo, A. Gaglione, C. L. Busceti, L. Ryskalin, G. Bozza, F. Nicoletti, F. Orzi, Francesco Fornai

Research output: Contribution to journalArticle

Abstract

The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.

Original languageEnglish
Pages (from-to)110-117
Number of pages8
JournalArchives Italiennes de Biologie
Volume155
Issue number3
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Apomorphine
Middle Cerebral Artery Infarction
Basal Ganglia
Muscle Strength
Neuroprotective Agents
Manuscripts
Dopamine Agonists
Middle Cerebral Artery
Brain Ischemia
Axons
Theoretical Models
Ischemia
Neurons
Proteins

Keywords

  • Apomorphine
  • Dopamine
  • Infarct volume
  • Middle cerebral artery occlusion
  • Permanent cerebral ischemia
  • Transient cerebral ischemia

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models. / Mastroiacovo, F.; Gaglione, A.; Busceti, C. L.; Ryskalin, L.; Bozza, G.; Nicoletti, F.; Orzi, F.; Fornai, Francesco.

In: Archives Italiennes de Biologie, Vol. 155, No. 3, 01.01.2017, p. 110-117.

Research output: Contribution to journalArticle

@article{31c7406be66b488fbf869701c8a5692d,
title = "A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models",
abstract = "The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.",
keywords = "Apomorphine, Dopamine, Infarct volume, Middle cerebral artery occlusion, Permanent cerebral ischemia, Transient cerebral ischemia",
author = "F. Mastroiacovo and A. Gaglione and Busceti, {C. L.} and L. Ryskalin and G. Bozza and F. Nicoletti and F. Orzi and Francesco Fornai",
year = "2017",
month = "1",
day = "1",
doi = "10.12871/00039829201732",
language = "English",
volume = "155",
pages = "110--117",
journal = "Archives Italiennes de Biologie",
issn = "0003-9829",
publisher = "Pisa University Press",
number = "3",

}

TY - JOUR

T1 - A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models

AU - Mastroiacovo, F.

AU - Gaglione, A.

AU - Busceti, C. L.

AU - Ryskalin, L.

AU - Bozza, G.

AU - Nicoletti, F.

AU - Orzi, F.

AU - Fornai, Francesco

PY - 2017/1/1

Y1 - 2017/1/1

N2 - The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.

AB - The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.

KW - Apomorphine

KW - Dopamine

KW - Infarct volume

KW - Middle cerebral artery occlusion

KW - Permanent cerebral ischemia

KW - Transient cerebral ischemia

UR - http://www.scopus.com/inward/record.url?scp=85037678623&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037678623&partnerID=8YFLogxK

U2 - 10.12871/00039829201732

DO - 10.12871/00039829201732

M3 - Article

AN - SCOPUS:85037678623

VL - 155

SP - 110

EP - 117

JO - Archives Italiennes de Biologie

JF - Archives Italiennes de Biologie

SN - 0003-9829

IS - 3

ER -