Neuroprotective effect of epidermal growth factor plus growth hormone-releasing peptide-6 resembles hypothermia in experimental stroke.
BACKGROUND
Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose.


OBJECTIVE
The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke.


METHODS
(a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups - vehicle, EGF + GHRP-6, and hypothermia - were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume.


RESULTS
(a) In global ischemia, neurological score at 48-72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group.


CONCLUSIONS
With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy.
a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
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N
Subirós
a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
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H
Pérez-Saad
a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
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Aldana
b Department of Neuroscience, Psychology and Behaviour , University of Leicester , Leicester , UK.
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Gibson
c Department of Periodontics and Oral Medicine , University of Michigan School of Dentistry , Ann Arbor , MI , USA.
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Borgnakke
a Biomedical Research Division , Center for Genetic Engineering and Biotechnology , Havana , Cuba.
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D
Garcia-Del-Barco
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005849:Gerbillinae; D013007:Growth Hormone-Releasing Hormone / Q000627:therapeutic use*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D020521:Stroke / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013007:Growth Hormone-Releasing Hormone
Combination therapy; EGF: Epidermal Growth Factor; Experimental stroke; GHRP-6: Growth Hormone-Releasing Peptide 6; Hypothermia; Ischemic stroke; Mongolian gerbils; Neurological score; Neuroprotectant; Wistar rats