{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:30:24Z","timestamp":1775219424899,"version":"3.50.1"},"reference-count":53,"publisher":"Cambridge University Press (CUP)","issue":"3","license":[{"start":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T00:00:00Z","timestamp":1526256000000},"content-version":"unspecified","delay-in-days":13,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Neurol. Sci."],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Because most tested drugs are active against only one of the damaging processes associated with stroke, other mechanisms may cause cellular death. Thus, a combination of protective agents targeting different pathophysiological mechanisms may obtain better effects than a single agent. The major objective of this study was to investigate the effect of combination therapy with vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) after controlled ischemic brain injury in rabbits.<jats:bold><jats:italic>Methods:<\/jats:italic><\/jats:bold>Animals were randomly assigned to one of the following groups: sham group, saline-treated control group or NGF+VEGF-treated group. Animals received an intracerebral microinjection of VEGF and NGF or saline at 5 or 8 hours after ischemia. The two specified time points of administration were greater than or equal to the existing therapeutic time window for monoterapy with VEGF or NGF alone (3 or 5 hours of ischemia). Infarct volume, water content, neurological deficits, neural cell apoptosis and the expression of caspase-3 and Bcl-2 were measured.<jats:bold><jats:italic>Results:<\/jats:italic><\/jats:bold>Compared with saline-treated controls, the combination therapy of VEGF and NGF significantly reduced infarct volume, water content, neural cell apoptosis and the expression of caspase-3, up-regulated the expression of Bcl-2 and improved functional recovery (both<jats:italic>p<\/jats:italic>&lt;0.01) when administered 5 or 8 hours after ischemia. The earlier the administration the better the neuroprotection.<jats:bold><jats:italic>Conclusions:<\/jats:italic><\/jats:bold>These results showed that the combination therapy with VEGF and NGF provided neuroprotective effects. In addition, the time window of combination treatment should be at least 8 hours after ischemia, which was wider than monotherapy.<jats:bold><jats:italic>R\u00c9SUM\u00c9:<\/jats:italic><\/jats:bold><jats:bold>Les effets d\u2019une polyth\u00e9rapie combinant agents neuro-protecteurs et agents vasoprotecteurs dans les cas d\u2019isch\u00e9mie c\u00e9r\u00e9brale.<\/jats:bold><jats:italic><jats:bold>Contexte:<\/jats:bold><\/jats:italic>\u00c9tant donn\u00e9 que la plupart des m\u00e9dicaments pr\u00e9alablement test\u00e9s tendent \u00e0 n\u2019agir contre seulement un des processus de dommage associ\u00e9s aux AVC, il est possible que d\u2019autres processus entra\u00eenent une mort cellulaire. \u00c0 cet effet, il se pourrait qu\u2019une combinaison d\u2019agents protecteurs ciblant divers m\u00e9canismes physiopathologiques permette d\u2019obtenir de meilleurs r\u00e9sultats qu\u2019un simple agent. Apr\u00e8s avoir suscit\u00e9 de fa\u00e7on contr\u00f4l\u00e9e des l\u00e9sions c\u00e9r\u00e9brales isch\u00e9miques chez des lapins, l\u2019objectif principal de la pr\u00e9sente \u00e9tude a donc \u00e9t\u00e9 de se pencher sur l\u2019impact d\u2019une polyth\u00e9rapie combinant la prot\u00e9ine dite \u00ab facteur de croissance de l\u2019endoth\u00e9lium vasculaire \u00bb (ou \u00ab VEGF \u00bb en anglais) avec le \u00ab facteur de croissance des nerfs \u00bb (ou \u00ab NGF \u00bb en anglais).<jats:italic><jats:bold>M\u00e9thodes:<\/jats:bold><\/jats:italic>Les animaux ont \u00e9t\u00e9 attribu\u00e9s au hasard \u00e0 l\u2019un des groupes suivants : ceux ayant re\u00e7u un traitement fictif ; ceux, du groupe t\u00e9moin, ayant b\u00e9n\u00e9fici\u00e9 d\u2019un traitement \u00e0 base de solution saline ; et finalement ceux ayant \u00e9t\u00e9 trait\u00e9s au moyen des VEGF et NGF. \u00c0 noter que les lapins ont re\u00e7u une micro-injection intrac\u00e9r\u00e9brale de VEGF et de NGF ou de solution saline 5 heures ou 8 heures \u00e0 la suite de leur AVC. Ces deux d\u00e9lais d\u2019administration des VEGF et NGF sont \u00e9quivalents ou sup\u00e9rieurs aux d\u00e9lais actuels d\u2019administration des VEGF ou NGF \u00e0 titre de monoth\u00e9rapie (3 heures ou 5 heures \u00e0 la suite d\u2019un AVC). Tant le volume des infarctus, le contenu en eau, les d\u00e9ficits neurologiques ainsi caus\u00e9s, l\u2019apoptose des neurones que l\u2019expression des prot\u00e9ases caspase 3 et des prot\u00e9ines Bcl-2 ont \u00e9t\u00e9 mesur\u00e9s.<jats:italic><jats:bold>R\u00e9sultats:<\/jats:bold><\/jats:italic>Si on la compare au traitement \u00e0 base de solution saline administr\u00e9 au groupe t\u00e9moin, la polyth\u00e9rapie \u00e0 base de VEGF et de NGF, lorsqu\u2019administr\u00e9e 5 heures ou 8 heures \u00e0 la suite de l\u2019AVC, a su r\u00e9duire de fa\u00e7on notable le volume des infarctus, le contenu en eau, l\u2019apoptose des neurones et l\u2019expression des prot\u00e9ases caspase 3. Elle a \u00e9galement permis de r\u00e9guler \u00e0 la hausse l\u2019expression des prot\u00e9ines Bcl-2 en plus d\u2019entra\u00eener une am\u00e9lioration de la r\u00e9cup\u00e9ration fonctionnelle (<jats:italic>p<\/jats:italic>&lt; 0,01 pour ces deux aspects). Ainsi donc, plus t\u00f4t l\u2019on opte pour cette polyth\u00e9rapie, meilleure sera la neuroprotection encourue.<jats:italic><jats:bold>Conclusions:<\/jats:bold><\/jats:italic>Ces r\u00e9sultats d\u00e9montrent que la polyth\u00e9rapie \u00e0 base de VEGF et de NGF procure des effets neuroprotecteurs. Quant au d\u00e9lai d\u2019administration de ce traitement combinatoire, il devrait \u00eatre d\u2019au moins 8 heures \u00e0 la suite d\u2019un AVC, ce qui est plus \u00e9lev\u00e9 que la monoth\u00e9rapie.<\/jats:p>","DOI":"10.1017\/cjn.2018.8","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T09:46:33Z","timestamp":1526291193000},"page":"325-331","source":"Crossref","is-referenced-by-count":8,"title":["Effect of Combination Therapy with Neuroprotective and Vasoprotective Agents on Cerebral 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