Effects of Poly (ADP-ribose) Polymerase Inhibitor on Hypoxic-ischemic Injury in the Neonatal Rat Brain: 1H Magnetic Resonance Spectroscopic Study / 대한마취과학회지

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) has been described as an important candidate for mediation of neurotoxicity after brain ischemia. This study was purposed to evaluate the effects of a PARP inhibitor on hypoxic-ischemic injury in the neonatal rat brain. In this study, a highly potent inhibitor of PARP, 3, 4-Dihydro-5-[4-(1-piperidinyl) butoxy]-1 (2H)-isoquinolinone (DPQ) was investigated. METHODS: Seven-day old Sprague-Dawley rat pups were used. The right common carotid artery was ligated under halothane anesthesia. After a recovery period of 3 hours, they were exposed to 8% oxygen at 37degreesC for about 120 minutes. The animals were divided into four groups: the pre-treatment group (n = 13) and post-treatment group (n = 21) were given DPQ 10 mg/kg and the pre-control group (n = 7) and post-control group (n = 14) were given a vehicle for controls. Pre-treatment and pre-control groups were injected 30 minutes prior to the hypoxic injury while post-treatment and post-control groups were injected 30 minutes after the hypoxic period intraperitoneally. The right cerebral hemisphere of the rats were examined with localized (1)H magnetic resonance spectroscopy on day 1 and 7 after the hypoxic insult. Lipid/N-acetyl aspartate (Lip/NAA) and lipid/creatine (Lip/Cr) ratios were used as apoptotic markers. On day 14, the degree of brain injury was scored by morphological changes. RESULTS: In the DPQ treated groups, the Lip/NAA and Lip/Cr ratios were lower than those of the control groups on day 1 after the hypoxic-ischemic injury (P < 0.05). However on day 7, only the ratios of the pre-treatment group were lower than those of the control group (P < 0.05). The degree of morphological changes of the brain injury on day 14 were lower in the DPQ treated groups (P < 0.05). CONCLUSIONS: These results suggest that DPQ exerts a neuroprotective effect in cerebral hypoxic-ischemic injury probably by inhibiting apoptosis especially in the early stage after an insult. Acute inhibition of PARP can have a therapeutic value in preventing ischemic brain injury.

Effects of Nitric Oxide Synthase Inhibitior on Energy Metabolism in Acute Ischemic-Reperfused Cat Brain: Investigated by 31P and 1H Magnetic Resonance Spectroscopy / 대한마취과학회지

BACKGROUND: The effects of the inhibitor of nitric oxide synthase (NOS) in cerebral ischemia have been debated. Recently, it has been suggested that it depends on the amount of the inhibitor used. Therefore, this study was carried out to evaluate the effects of the NOS in the acute ischemia-reperfusion of the cat model using variable amounts of the inhibitor. METHODS: Nineteen cats were divided into 3 groups: group 1 (n = 6), 10 mg/kg of N-nitro-L-arginine methyl ester (L-NAME); group 2 (n = 7), 0.5 mg/kg; group 3 (n = 6), control group. Incomplete global cerebral ischemia was induced by ligation of both carotid arteries with arterial hypotension (-40 mmHg) for 30 minutes followed by 3 hours of reperfusion. The NOS inhibitor (L-NAME), was injected intraperitoneally 5 minutes before reperfusion. 31P and 1H MR spectroscopy were performed. A series of spectra was acquired in the time intervals before ligation, during ischemia, and after reperfusion. RESULTS: Phosphocreatine/inorganic phosphate (PCr/Pi) ratios for group 1 were significantly lower than for groups 2 and 3 (P < 0.05), and there was no significant difference between groups 2 and 3. Lactate/N-acetyl aspartate (Lac/NAA) and lactate/creatine (Lac/Cr) ratios at 180 minutes after reperfusion were higher for group 1 than for groups 2 and 3 (P < 0.05). There were no significant differences in pH and lactate/choline (Lac/Cho) ratios among the 3 groups. CONCLUSIONS: It is demonstrated that the effect of the NOS inhibitor is dosage dependent. A high dose (10 mg/kg) of L-NAME seems to have an adverse effect on recovery of the ischemia, but a low dose (0.5 mg/kg) seems to have no effect.

In Vivo Proton MR Spectroscopic Change of Experimental Rat Brain Abscess Model

OBJECTIVE: This study was designed to clarify the phasic changes and distinctive spectral features of the brain abscess in the in vivo proton MR spectroscopy during the processes of abscess formation in rats, in relation to MR images. METHODS: Staphylococcus aureus was stereotactically inoculated into the predetermined location of the right frontal brain of SPF controlled Sprague-Dawley female rats(200-250gm). T1 weighted image(WI), T2WI and gadolinium enhanced image(CEMR) were obtained serially prior to each MR spectroscopy in order to visualize the infected lesions. RESULT: Three characteristic peaks, from proton MR spectroscopy, were found. A dominant peak was shown at 1.3ppm, which was due to the high concentration of mobile lipid or lactate, and smaller two peaks were shown at 0.8-1.0ppm and 1.9ppm, due to the small concentration of aminoacid(leucine, isoleucine. valine) and acetate, respectively. The lactate peak has increased during the stage of cerebritis and started to decrease in its early capsulation stage, finally invisible in its late capsulation stage(p=0.0001). The change of lactate peak was conspicuous at the early stage of cerebritis while the change of MR image was rather subtle. The aminoacids peak remained small throughout all stages. The acetate peak was shown in the late stage of cerebritis. However, it's peak area of integration was not exactly measured because of overlapping on the N-acetylaspartate peak. On the other hand, the peak of N-acetylaspartate and creatines, which could be observed in normal brain, remained at low level after sharp decrease in the early stage of cerebritis(p=0.004, p=0.005). The cholines peak decreased in the early stage of cerebritis, but it was not statistically significant(p=0.124). CONCLUSION: From this study, we were able to observe the characteristic MR spectroscopic features of each stage even from such a small volume of abnormal lesions with a 2X2X3mm 3 voxel size. Furthermore, based on our results that inflammatory change could be detected earlier by MR spectroscopy than by MR images, MR spectroscopy may be applied for early diagnosis of the brain abscess.

Effects of Mg2+ Intravenous Pretreatment on Brain Energy Metabolism in Acute Ischemic-Reperfusion Model in Cats: 31P and 1H Magnetic Resonance Spectroscopic Study / 대한구급학회지

BACKGOUND: This study was purposed to evaluate the effects of Mg2+ pretreatment on cerebral ischemic injury in cats. METHODS: Global cerebral ischemia was induced by ligation of both innominate arteries following ligation of inferior vena cava under lowered mean blood pressure for 20 minutes followed by 3 hrs of reperfusion. Ten cats were divided into 2 groups: Group 1 (n=5) is the control group, for group 2 (n=5) (Mg2+ group), the animals were pretreated with 90 mg/kg of Mg2+ intravenously before subjected to ischemia. RESULTS: Phosphocreatine/inorganic phosphate (Pcr/Pi) and pH decreased after ischemia and did not recovered during reperfusion. And there were no significant differences between the two groups. The ratios of lactate/N-acetyl aspartate (Lac/NAA) and lactate/creatine (Lac/Cr) increased after ischemia and not recovered during reperfusion. But the ratios were higher for the group 2 than the group 1 during reperfusion (p<0.05). For the Mg2+ group, blood pressure during reperfusion was lower than the control group. CONCLUSIONS: Mg2+ intravenous pretreatment had no protective effect on this global cerebral ischemia animal model. Even it deteriorated brain energy metabolism by lowering blood pressure.

Effects of the Level of PaCO2 on Recovery of Energy Metabolism: Is Normocarbia or Hypocarbia Better for Ischemia-Reperfused Cat Brain? / 대한마취과학회지

BACKGROUND: The effect of arterial carbon dioxide tension (PaCO2) during ischemia and reperfusion has been a controversial issue. In this study, the effect of PaCO2 during ischemia and reperfusion was evaluated by 31P magnetic resonance spectroscopy (MRS). METHODS: Incomplete global cerebral ischemia was induced by ligation of carotid artery under lowered mean blood pressure (mean blood pressure= 40 mmHg) for 30 minutes followed by 2 hours of reperfusion. Eighteen cats were divided into 3 groups: For group 1 (n=6) (control group), animals were subjected to normocarbia (PaCO2=28~33 mmHg) during ischemia and reperfusion, for group 2 (n=6), animals were subjected to hypocarbia (PaCO2=18~23 mmHg) during ischemia and reperfusion, and for group 3 (n=6), animals were subjected to normocarbia during ischemia and hypocarbia during reperfusion. RESULTS: For group 1, the energy metabolism measured by [PCr/Pi] was recovered about 74.7 6.4%. For group 2, the energy metabolism failed to be completely recovered by 120 minutes of reperfusion (69.3 7.3%), whereas for group 3, the energy matabolism was completely recovered by 120 minutes of reperfusion (97.6 2.4%). There were statistically significant differences between group 1 and group 3 (p<0.05). The changes in pH were not significantly different among the groups. CONCLUSION: In this study, a condition of hypocarbia during reperfusion seems better for the energy metabolism after incomplete global ischemia of cats.