Neuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion.
This study examined the neuroprotective effects of magnesium-sulfate (MgSO(4)) on the cerebral blood flow (CBF) and extracellular glutamate concentration in an eleven vessel occlusion (11VO) rat model. Twenty-one male Sprague-Dawley rats (250-350g) were used for the 11VO ischemic model, which was induced by a 10-min transient occlusion. The animals were divided into 3 groups, including ischemic-induced animals (ischemia group), ischemic-induced and MgSO(4) treated animals (MgSO(4) group), and sham animals for comparison. The real-time extracellular glutamate concentration was measured using a microdialysis biosensor, and the CBF was monitored by laser Doppler flowmetry. Neuronal cell death in the hippocampal region was observed 72h after ischemia by several stains (Nissl, DAPI, NeuN, and cleaved caspase3). A significant decrease in %CBF was observed in both the ischemia and MgSO(4) groups, such as ~10% during the ischemic period. However, the MgSO(4) group showed a significant decrease in the initial reperfusion %CBF compared to the ischemia group. A significantly lower level of glutamate release was observed in the MgSO(4) group than in the ischemia group during the ischemic and reperfusion episode. Our staining results revealed a significant decrease in neuronal cell death in the hippocampus in the MgSO(4) group compared to the ischemia group. These results suggest that MgSO(4) is responsible for the protection of neuronal cells by suppressing the release of extracellular glutamate under ischemic conditions and the CBF response during the initial reperfusion period.
Department of Biomedical Engineering and Healthcare Industry Research Institute, College of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Sung Wook
SW
Kang
Seok-Keun
SK
Choi
Eunkuk
E
Park
Su-Jin
SJ
Chae
Samjin
S
Choi
Hyo
H
Jin Joo
Gi-Ja
GJ
Lee
Hun-Kuk
HK
Park
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D018698:Glutamic Acid / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D016037:Single-Blind Method
D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; C546339:Rbfox3 protein, rat; D018698:Glutamic Acid; D008278:Magnesium Sulfate; C505410:Casp3 protein, rat; D053148:Caspase 3