Abstract
EFFECTS OF THE INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND 17β-ESTRADIOL AFTER A TRANSIENT FOCAL CEREBRAL ISCHEMIA IN THE ENDOTHELIN-1 RAT MODEL.
Stoop Wendy1, De Geyter Deborah1, Sarre Sophie2, Kooijman Ron1.
1 Department of Pharmacology, 2 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Introduction: Stroke is the first cause of morbidity in the European Union and worldwide it is the leading cause of adult disability. To date, thrombolytic therapy using recombinant tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, only 5-10% of all patients benefit from this treatment because of the inclusion criteria. Targeting different processes involved in the ischemic cascade, which include excitotoxicity, oxidative stress, inflammation and cell death, could be promising for the future of stroke treatment. IGF-I is an anti-apoptotic pleiotropic factor exerting effects on different levels of the ischemic cascade. It has been shown in both in vitro and vivo models that the neuroprotective effects of the IGF-IR and ER or interdependent. This interdependency creates the possibility to increase the efficacy of IGF-I treatment with estradiol, also a neuroprotective agent.
Aim: Possible synergistic effects of IGF-I and 17β-estradiol (E2) will be studied in the endothelin (Et)-1 rat model for stroke. Effects on both infarct size and functional outcome will be investigated.
Material and methods: Via a guide cannula implanted using stereotactic surgery, 200 pmol Et-1 was administered in the vicinity of the middle cerebral artery of male albino Wistar Kyoto (WKY) rats. Rats were treated with estradiol/vehicle (1mg/kg, 0.2 ml s.c.) and IGF-I/vehicle (3mg/kg, 0.2 ml, s.c.) 30 min after the induction of stroke. Motor/sensory functions were determined 24 h after the insult using the neurological deficit score (NDS). Infarct size was assessed using a cresylviolet staining.
Results: Treatment with both E2 and IGF-I 30 min after the induction of stroke resulted in a significant reduction in infarct size (22.19 ± 4.35 mm³) when compared to the vehicle treated animals (65.36 ± 5.49 mm³). Rats treated with E2 (48.89 ± 12.28 mm³) or IGF-I (40.98 ± 4.21 mm³) alone showed smaller infarct sizes, however not significant. Further experiments to increase the number of rats have to be performed to make further conclusions.
Conclusion: A combination of both estradiol and IGF-I seems to reduce infarct size after a transient focal cerebral ischemia in the Et-1 rat model. However, other parameters such as e.g. microglial activation will still be analysed in this study.
Stoop Wendy1, De Geyter Deborah1, Sarre Sophie2, Kooijman Ron1.
1 Department of Pharmacology, 2 Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
Introduction: Stroke is the first cause of morbidity in the European Union and worldwide it is the leading cause of adult disability. To date, thrombolytic therapy using recombinant tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, only 5-10% of all patients benefit from this treatment because of the inclusion criteria. Targeting different processes involved in the ischemic cascade, which include excitotoxicity, oxidative stress, inflammation and cell death, could be promising for the future of stroke treatment. IGF-I is an anti-apoptotic pleiotropic factor exerting effects on different levels of the ischemic cascade. It has been shown in both in vitro and vivo models that the neuroprotective effects of the IGF-IR and ER or interdependent. This interdependency creates the possibility to increase the efficacy of IGF-I treatment with estradiol, also a neuroprotective agent.
Aim: Possible synergistic effects of IGF-I and 17β-estradiol (E2) will be studied in the endothelin (Et)-1 rat model for stroke. Effects on both infarct size and functional outcome will be investigated.
Material and methods: Via a guide cannula implanted using stereotactic surgery, 200 pmol Et-1 was administered in the vicinity of the middle cerebral artery of male albino Wistar Kyoto (WKY) rats. Rats were treated with estradiol/vehicle (1mg/kg, 0.2 ml s.c.) and IGF-I/vehicle (3mg/kg, 0.2 ml, s.c.) 30 min after the induction of stroke. Motor/sensory functions were determined 24 h after the insult using the neurological deficit score (NDS). Infarct size was assessed using a cresylviolet staining.
Results: Treatment with both E2 and IGF-I 30 min after the induction of stroke resulted in a significant reduction in infarct size (22.19 ± 4.35 mm³) when compared to the vehicle treated animals (65.36 ± 5.49 mm³). Rats treated with E2 (48.89 ± 12.28 mm³) or IGF-I (40.98 ± 4.21 mm³) alone showed smaller infarct sizes, however not significant. Further experiments to increase the number of rats have to be performed to make further conclusions.
Conclusion: A combination of both estradiol and IGF-I seems to reduce infarct size after a transient focal cerebral ischemia in the Et-1 rat model. However, other parameters such as e.g. microglial activation will still be analysed in this study.
| Original language | English |
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| Title of host publication | Belgian Belgian society of fundamental and clinical physiology and pharmacology. Spring meeting |
| Publication status | Published - 16 Mar 2012 |
| Event | Belgian Belgian society of fundamental and clinical physiology and pharmacology. Spring meeting - , United Kingdom Duration: 16 Mar 2012 → … |
Concert
| Concert | Belgian Belgian society of fundamental and clinical physiology and pharmacology. Spring meeting |
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| Country/Territory | United Kingdom |
| Period | 16/03/12 → … |