Evaluation of neuroprotective effect by the type II metabotropic glutamate receptor agonist in the rat ischemic models.

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: University of Yamanashi
• Principal Investigator: SUGITA Masao University of Yamanashi, University of Yamanashi Hospital, Assistant Professor, 医学部附属病院, 講師 (70235886)
• Project Period (FY): 2004 – 2005
• Keywords: glutamate receptor / metabotropic receptor / cerebral infarction / microdialysis / agonist / DCG-IV / rat / delayed neuronal death

Research Abstract

Objectives : To determine the neuroprotective effect of the type II metabotropic glutamate receptor agonist, we have evaluated the DCG-IV (2-(2',3')-dicarboxycyclopropylglycine) in rat brain ischemia models of middle cerebral occlusion and transient global ischemia.
Methods : As an acute focal ischemia model, we have chosen the intraluminal thread model of middle cerebral occlusion. DCG-IV (5-500nmol) or saline was administrated via intracerebral irrigation probe Under a general anesthesia, focal cerebral ischemia was induced by 4-0 nylon suture insertion via the right common carotid artery. After 1 hour of ischemia, inserted suture was removed and occluded artery was recanalized. Then 2 hours of recirculation, the rat was anesthetized again and decapitated. The brain was rapidly removed and the volume of infarction was calculated by TTC staining. To analyze the effect of DCG-IV for the delayed neuronal death, pretreatment with intraventricular adminiatration of DCG-IV (10-500pmol) was performed. The transient global ischemia was induced by hypotension and bilateral carotid artery occlusion. Five minutes of global ischemia, blood pressure was reversed and occlusion was released. After 5 days of global ischemia, rat brain was removed and the hyppocampal CA1 pyramidal cells was counted to evaluate delayed neuronal death.
Results : In the focal ischemia model, the infarction volume of 1 hour ischemia with 2 hours reperfusion was not different with or without DCG-IV administration. However, in the transient global ischemia model, significant larger number of the hyppocampal CA1 pyramidal cells were observed in the DCG-IV treated group in a dose dependent manner.
Conclusion : These results suggested that the stimulation of type II metabotropic glutamate receptor has the effect of neuroprotection for the delayed neuronal death caused by transient global ischemia and not for the acute focal ischemic damage in the rat.