Effect of Melatonin on the Changes of Hippocampal Polyamine Content and Neuronal Damage Following Transient Global Ischemia in Mongolian Gerbil: a Study of the Differences of Pre- and Post-ischemic Treatment / 대한마취과학회지

BACKGROUND: We designed this study to examine whether melatonin has a neuroprotective effect against hippocampal neuronal damage following transient global ischemia in a gerbil. Because polyamine is known to participate in the process of ischemic neuronal damage, we examined the influence of melatonin on the polyamine level as well as histology. In particular, we examined the difference between pre- and post-ischemic treatments of melatonin by using the above mentioned parameters. METHODS: Male Mongolian gerbils (60 - 80 g) were used in this study. Transient global ischemia was induced by occlusion of the bilateral common carotid arteries for 3 min with microclips. Melatonin was administered 1 h before or 1 h after occlusion. The animals were dissected 4 days after the occlusion for polyamine measurement by a high performance liquid chromatography (HPLC) and histological evaluation (hematoxylin and eosin staining). A histological examination was performed by a blinded investigator. RESULTS: The hippocampal putrescine (PU) level increased compared to sham-operated animals and the increase of PU was attenuated by melatonin administration (pre- or post-ischemic treatment). Spermidine (SD) and spermine (SM) levels didn't show significant changes after ischemia. Hippocampal neuronal damage in the CA1 region was markedly observed in vehicle-treated animals compared to sham- operated animals. Both pre- and post-ischemic melatonin administration significantly inhibited hippocampal CA1 neuronal damage compared to corresponding vehicle-treated animals (P < 0.01, respectively). CONCLUSIONS: Melatonin attenuates the polyamine response following transient global ischemia and may have putative neuroprotective effects against global ischemia-induced neuronal damage. There is no difference in neuroprotective effects of melatonin between pre- & post-ischemic treatments.

Effect of Fentanyl on the TNF-alpha and IL-1beta Level during Global Ischemia/reperfusion in Rats / 대한마취과학회지

BACKGROUND: To reduce surgical stress, fentanyl is frequently used for neurosurgical procedure where focal and/or global ischemia may occur. However, the effect of fentanyl on the cytokine level during ischemia/reperfusion is still uncertain. The goal of this study was to evaluate the effect of fentanyl infusion on the proinflammatory cytokine, TNF-alpha and IL-1beta, levels during global cerebral ischemia/reperfusion (I/R) in rats using the intracerebral microdialysis technique. METHODS: Forty male S-D rats weighing 280 320 g were randomly assigned to four groups. Group 1: no fentanyl infusion and only I/R, Group 2: 1.5 ng/ml of fentanyl infusion during I/R, Group 3: 3.0 ng/ml of fentanyl infusion during I/R (n = 10 in each group). Rats were anesthetized with a intraperitoneal injection of pentobarbital (50 mg/kg), intubated and ventilated with room air using an animal ventilator. Two femoral arteries and one femoral vein were cannulated with PE-50 tubing for hemorrhagic hypotension, drug infusion and hydration. Both carotid arteries were dissected and a sling was placed for brain ischemia. The head was fixed on a stereotaxic device and a small burrhole was made for probe insertion. A CMA-12 probe was inserted into the left hippocampal CA-1 region according to the guidelines. Artificial CSF was run from the inserted microdialysis probe and infused with or without fentanyl at 3 microliter/min using a microinjection syringe pump during I/R. Ischemia was induced by clamping the carotid arteries while hemorrhagic hypotension for 17 min via the femoral artery and reperfusion were accomplished by the unclamping of the sling and reinfusing the blood via the femoral artery. Nasopharyngeal and rectal temperatures were maintained within the normal range during the whole procedure. After 2 hours of stabilization, the microdialysate was collected every 17 min just before (control) and during I/R and stored at 80oC until analysis using HPLC. RESULTS: During global I/R, TNF-alpha and IL-1 beta significantly increased at reperfusion (R5) compared to the control value (P < 0.05). However, in both cases of fentanyl infusion, TNF-alpha and IL-1 beta did not increase compared to the control value. CONCLUSIONS: Fentanyl inhibited the increase of proinflammatory cytokine TNF-alpha and IL-1 beta levels during global cerebral ischemia/reperfusion in rats.

Effects of Nitric Oxide Synthase Inhibition on Hydroxyl Radical Production during Global Cerebral Ischemia/Reperfusion in Rats / 대한마취과학회지

BACKGROUND: Free radical-mediated oxidative damage has been implicated in ischemic brain injury. There are also increasing evidences that nitric oxide is involved in the mechanisms of cerebral ischemia. To elucidate the effect of nitric oxide synthesis inhibition on the hydroxyl radical formation, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3-DHBA following salicylate adminstration. METHODS: Sprague-Dawley rats were subjected to 15 min of global cerebral ischemia by both carotid artery occlusion plus systemic hemorrhagic hypotension (35 mmHg). Artificial CSF including salicylate (5 mM) was continuously infused through a microdiaysis probe implanted in the left hippocampus CA1. Hippocampal extracellular fluid was sampled at regular intervals before, during, and after ischemia. The levels of 2,3-DHBA were assayed by HPLC with electrochemical detection during 15 minutes of ischemia and reperfusion period. RESULTS: Cerebral blood flow was reduced to 5% level of control in ischemic period, but increased 3 or 4 times in early phase of reperfusion period, and returned to normal 50 to 60 minutes after the cessation of ischemia. Inhibition of NOS by L-NAME did not prevent ischemia-induced 2,3-DHBA elevation, but increased its level during reperfusion. This increase in 2,3-DHBA could be reversed by L-arginine. The elevated 2,3-DHBA after IR in L-NAME treated rats was not due to either changes in CBF or local blood brain barrier permeability. CONCLUSIONS: The above results indicate NO protects brain from damages by hydroxyl radical, at least less than one hour after initiation of reperfusion.