Delayed administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, improves cerebral blood flow and metabolism in rat postischaemic brain
T. Katsumata et al., Delayed administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, improves cerebral blood flow and metabolism in rat postischaemic brain, CLIN EXP PH, 28(1-2), 2001, pp. 48-54
Citations number
27
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
1. The aim of the present study was to examine the central nervous system a
ction of JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue, fr
om the point of view of cerebral blood flow (CBF) and metabolism in the pos
tischaemic brain.
2. Left middle cerebral artery ischaemia was induced for 90 min followed by
reperfusion.
3. Animals were separated into four groups: (i) low-dose (0.003 mg/kg) JTP-
2942; (ii) high-dose (0.03 mg/kg) JTP-2942; (iii) cystidine diphosphate cho
line (500 mg/kg); and (iv) saline. The test drug or saline was administered
intravenously 1 week after ischaemia,
4. Local CBF and local cerebral glucose utilization were measured autoradio
graphically, adjacent sections were stained with haematoxylin-eosin and inf
arction size was measured.
5. JTP-2942 ameliorated the reduction of local CBF and glucose utilization
except in the ischaemic core. In particular, the higher dose (0.03 mg/kg) o
f JTP-2942 significantly increased local CBF and glucose utilization not on
ly in peri-infarcted areas, but also in distal and contralateral areas.
6. These results suggest that JTP-2942 treatment may be beneficial for impr
oving cerebral circulation and metabolism in the postischaemic brain.