The effect of
JTP-2942, a novel
thyrotropin-releasing hormone analogue on neurological examination, local cerebral blood flow (l-CBF) and local cerebral
glucose utilization (l-CGU) were examined when
JTP-2942 was administered for 4 weeks after 1 week reperfusion following
ischemia in a rat middle cerebral artery (MCA) occlusion. Left middle cerebral artery
ischemia was induced for 90 min followed by reperfusion.
JTP-2942 (0.03 or 0.003 mg/kg) or saline (vehicle) were administered for 4 weeks after 1 week
ischemia, and then the
drug was withdrawn. Neurological symptoms and motor disturbance based on inclined plane test were measured once a week after 1 week
ischemia. l-CBF and l-CGU were measured by quantitative autoradiographic technique after 6 weeks
ischemia. The adjacent sections subjected to l-CBF or l-CGU measurement were stained with
Hematoxylin-
Eosin, and the
infarction volume was measured.
JTP-2942 (0.03 mg/kg) significantly ameliorated neurological symptoms and motor disturbance at 5 weeks after
ischemia as compared with vehicle, and then after completion of
drug administration, amelioration effect continued.
JTP-2942 (0.03 mg/kg) also significantly ameliorated the reduced l-CBF and l-CGU in the peri-infarcted areas such as the frontal cortex, motor cortex and medial caudate-putamen. No significant differences were noted in the
infarction volume among MCA occlusion rats. This indicates that activating reduced metabolic turnover associated with synaptic connection changes or the activation of compensation mechanisms may result in improvement of neurological symptoms and motor disturbances. It is therefore expected that
JTP-2942 may be a possible therapeutic agent for motor disturbance during the subacute or chronic
cerebral infarction.