Delayed and chronic treatment with growth hormone after endothelin-induced stroke in the adult rat.
We investigated the effects of a neurorestorative treatment paradigm using long-term, central delivery of growth hormone (GH) starting 4 days after stroke. It has been shown previously that a neural GH axis is activated after stroke, that GH is neuroprotective, and can have direct trophic actions on neurons and stem cells. First, we developed and validated a buffer that kept rat GH bioactive for 2 weeks at body temperature. Implanted minipumps were used to chronically infuse GH into the lateral ventricle of unilateral stroke injured adult rats. Initially, a dose ranging pilot study was used to characterize the neuroendocrine effects and distribution of the infused GH. Next, a 6-week treatment trial starting 4 days after induction of the stroke was performed and the animals allowed to recover for a further 6 weeks. Behavioural and endocrinological measures were taken. We found that the infused GH localized to cells within the ipsilateral; subventricular zone, white matter tract, lesion and penumbral regions. GH treatment accelerated recovery of one out of three tests of motor function (P<0.001) and improved spatial memory on the Morris water maze test at the end of the study (P<0.05), with no effect on learning. We also found that GH treatment was associated with a reversible increase in body weight (P<0.01) whilst circulating IGF-1 (insulin-like growth factor 1) levels were halved (P<0.001). Delayed and chronic treatment of stroke with central GH may accelerate some aspects of functional recovery and improve spatial memory in the long-term.
Pathipati
Praneeti
P
Liggins Institute, University of Auckland, 2-6 Park Avenue, Grafton, Auckland, New Zealand. p.pathipati@auckland.ac.nz
Surus
Andrzej
A
Williams
Christopher Edward
CE
Scheepens
Arjan
A
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002021:Buffers; D002404:Catheterization; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D016232:Endothelins / Q000633:toxicity; D013006:Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D012720:Severity of Illness Index; D013028:Space Perception / Q000187:drug effects; D020521:Stroke / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
D002021:Buffers; D016232:Endothelins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003345:Corticosterone