Increased Formation of Reactive Oxygen Species after Permanent and Reversible Middle Cerebral Artery Occlusion in the Rat

Abstract

In barbiturate-anesthetized rats, we induced 3 hours of permanent middle cerebral artery occlusion (MCAO) by an intraluminal thread (n = 6), or 1 hour MCAO followed by 2 hours of reperfusion (n = 6). Through a closed cranial window over the parietal cortex, the production of reactive oxygen species (ROS) was measured in the infarct border using online in vivo chemiluminescence (CL) while monitoring the appearance of peri-infarct depolarizations (PID). The borderzone localization of the ROS and direct current (DC) potential measurements was confirmed in additional experiments using laser-Doppler scanning, mapping regional CBF changes through the cranial window after permanent (n = 5) or reversible (n = 5) MCAO. CL measurements revealed a short period (10 to 30 minutes) of reduced ROS formation after vessel occlusion, followed by a significant increase (to 162 +/- 51%; baseline = 100%; P < .05) from 100 minutes of permanent MCAO onward. Reperfusion after a 1-hour period of MCAO led to a burst-like pattern of ROS production (peak: 489 +/- 330%; P < .05). When the experiments were terminated 3 hours after induction of MCAO, CL was still significantly increased above baseline after permanent and reversible MCAO (to 190 +/- 67% and 211 +/- 64%, respectively; P < .05). Simultaneous DC potential recordings detected 6.4 +/- 2.7 PID in the first, 4.7 +/- 2.3 in the second, and 2.8 +/- 2.0 in the third hour after permanent MCAO. In animals with reversible MCAO, PID were abolished from 15-minutes recirculation onward. There was no temporal relationship between ROS production and peri-infarct DC potential shifts. In conclusion, using a high temporal resolution ROS detection technique (CL), we found that permanent MCAO (after an initial decrease) was accompanied by a steady increase of ROS production during the 3-hour observation period, while reperfusion after 1 hour of MCAO produced a burst in ROS formation. Both patterns of ROS production were not related to the occurrence of PID.

Effects of Edaravone on a Rat Model of Punch-Drunk Syndrome

“…10) However, AGE-positive cells were observed at 5 days after skull vibration, and edaravone administration reduced the number of AGE-positive cells through its radical-scavenging activity. Based on our previous report that skull vibration reduced cerebral surface blood flow in rats under the same experimental conditions as in this study, as well as a report that the amount of free radicals in the brain increased after experimental cerebral ischemiareperfusion, 12) we speculate that skull vibration under the present experimental conditions reduced cerebral blood flow, and reperfusion led to the production of free radicals.…”

Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury

“…Neutrophil influx occurs in the first 24 h after ischemia followed by monocyte migration from 24 h up to 5 days (Hallenbeck et al, 1986;Danton and Dietrich, 2003). The inflammatory response involves rolling, firm adhesion and transendothelial migration of leukocytes on the level of postcapillary venules, BBB dysfunction and increased production of proinflammatory mediators including reactive oxygen species, nitric oxide, cytokines, adhesion molecules and chemokines (Peters et al, 1998;Schuerer et al, 1994;Lindauer et al, 1996;Okada et al, 1994;Che et al, 2001;Yang et al, 1999). All of these mediators have been suggested as being involved in BBB 'breakdown' during inflammation, causing a dysfunction of TJ structure (abnormality in occludin and ZO-1), greater influx of blood-borne cells and further amplification of inflammation and brain parenchymal damage (Plumb et al, 2002;Gloor et al, 2001).…”

Nrf2 Activation, an Innovative Therapeutic Alternative in Cerebral Ischemia

“…However, free radical production in the penumbral zone increases during both events (Liu et al, 2003). Despite the low oxygen tension produced during ischemia, exist an increase in ROS formation after 1.6 h of ischemia, the highest ROS production (489 ± 330% of control) occurs after 20 min of reperfusion, and remains increased at least for 3 h (Peters et al, 1998). Christensen et al (1994) reported that ROS production is maximal during the first hour of reperfusion.…”

“…As previously described, physiopathological mechanisms leading to neuronal injury in cerebral stroke are complex and multifactorial. However, several studies suggest that oxidative stress, secondary to ROS and RNS production, actively participates during postischemic brain damage (Peters et al, 1998;Rodrigo et al, 2005). During ischemia, free radical production in the infarct zone decreases or remains without change, while it increases during reperfusion.…”