Incomplete Cerebral Ischemia In Rats Research Articles

Sevoflurane‐induced post‐conditioning has no beneficial effects on neuroprotection after incomplete cerebral ischemia in rats

The aim of this study was to investigate whether sevoflurane-induced post-conditioning has a neuroprotective effect against incomplete cerebral ischemia in rats. After cerebral ischemia by right common carotid artery occlusion in combination with hemorrhagic hypotension (35 mmHg) for 30 min, 1.0 minimum alveolar concentration of sevoflurane was administered for 15 min (Post-C 15, n=8), 30 min (Post-C 30, n=8), or 60 min (Post-C 60, n=8) in rats. Sevoflurane was not administered in control (n=8) and sham control rats (n=8). Neurologic evaluations were performed at 24, 48, and 72 h after ischemia. Degrees of neuronal damage in ischemic hippocampal CA1 and the cortex were assessed by counting eosinophilic neurons, and detection of DNA fragmentation was performed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Neurologic deficit scores in the Post-C 60 group were higher than in the control group at 48 and 72 h post-ischemia (P<0.05). No differences were observed in the percentages of eosinophilic neurons among the control (CA1: 37.3 +/- 25.4, cortex: 26.0 +/- 8.9), Post-C 15 (CA1: 54.0 +/- 21.4, cortex: 30.8 +/- 19.9), or Post-C 30 (CA1: 68.4 +/- 17.5, cortex: 38.0 +/- 11.0) groups in ischemic CA1 and cortices. However, in the Post-C 60 group, the percentages of eosinophilic neurons were higher than in the control group in CA1 and cortices (P<0.05). The percentages of TUNEL-positive cell were similar in the control group and the post-conditioned groups. These findings show that sevoflurane administration after ischemia does not provide neuroprotection in rats subjected to incomplete cerebral ischemia.

Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats

Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone. Thirty-eight male Sprague-Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 degrees C); group H (saline 1 ml/kg, 35.0 degrees C); group D (dexmedetomidine 100 microg/kg, 37.5 degrees C); and group DH (dexmedetomidine 100 microg/kg, 35.0 degrees C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia. Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05). The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone.

The Effects of Dexmedetomidine on Apoptosis-Regulating Proteins after Incomplete Cerebral Ischemia in Rats over Time

The Effects of Dexmedetomidine on Apoptosis-Regulating Proteins after Incomplete Cerebral Ischemia in Rats over Time

Ketamine decreases plasma catecholamines and improves outcome from incomplete cerebral ischemia in rats.

Central neuroexcitatory receptors (N-methyl-D-aspartate [NMDA], non-NMDA) may affect outcome from cerebral ischemia by altering sympathetic nervous system activity. We tested whether ketamine, an NMDA antagonist, and NBQX, a non-NMDA antagonist, improve outcome from incomplete cerebral ischemia in the rat and whether a change in outcome is related to changes in plasma catecholamines. There were five treatment groups: group 1 (control, n = 10) received a fentanyl infusion at a rate of 25 microgram.kg-1.h-1 and ventilation with 70% N2O in O2. Group 2 (n = 10) received the same anesthetic treatment and were given an intraperitoneal injection of 30 mg/kg NBQX 15 min prior to ischemia. Group 3 (n = 10) received a ketamine infusion of 1.0 mg.kg-1.min-1 and ventilation with room air. Group 4 (n = 10) received a ketamine infusion of 1.5 mg.kg-1.min-1. Group 5 received a ketamine infusion of 1 mg.kg-1.min-1 plus a 6 ml/kg intraperitoneal injection of 40% glucose solution 15 min before the start of ischemia. Ischemia was produced by right common carotid ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Blood gases, pH, and skull temperature were controlled during ischemia. Plasma glucose increased during ischemia in all groups but was lower in ketamine-anesthetized rats (groups 3 and 4). Glucose-loaded ketamine-anesthetized rats (group 5) had plasma glucose concentrations similar to the control group. Plasma epinephrine and norepinephrine concentrations were significantly less in ketamine-anesthetized rats (groups 3, 4, and 5) during ischemia compared to controls (P less than 0.05). Neurologic outcome was significantly better (P less than 0.05) in all ketamine-treated rats (groups 3, 4, and 5) compared to the control group, regardless of plasma glucose concentration during ischemia. NBQX did not improve neurologic outcome. These results suggest that ketamine improves neurologic outcome from incomplete cerebral ischemia by a mechanism related to a decrease in plasma catecholamine activity.

The Effects of Propofol on Brain Electrical Activity, Neurologic Outcome, and Neuronal Damage Following Incomplete Ischemia in Rats

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracarotid saline infusion improves outcome from incomplete ischemia in rats.

Previous studies suggest that rheological changes associated with ischemia may produce postischemic hypoperfusion. We tested whether intracarotid or intravenous infusions of saline improve neurological outcome from incomplete cerebral ischemia in rats. Rats were anesthetized with 1.4% isoflurane in air, and ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 minutes. Intracarotid (n = 10) or intravenous (n = 10) saline infusion (0.3 ml/min) decreased hematocrit 20% compared with control rats (n = 10). Neurological outcome was significantly improved in rats infused with intracarotid (p less than 0.05) but not intravenous saline during ischemia without a change in brain temperature. Cerebral blood flow, measured in a separate study using laser Doppler flowmetry (n = 5), decreased 70% (p less than 0.01) during carotid ligation and hypotension but was not changed by intracarotid saline infusion (p greater than 0.30). These results show that perfusion of ischemic brain with saline improves outcome by factors not related to changes in hematocrit, brain temperature, or intraischemic tissue blood flow.

Postischemic treatment with hypothermia improves outcome from incomplete cerebral ischemia in rats.

It is known that hypothermia can improve outcome when induced during ischemia. We evaluated whether hypothermia can decrease ischemic injury if it is induced after incomplete ischemia. Rats were anesthetized with 1.4% inspired isoflurane, and ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 min. Hypothermia (31 degrees C) was induced or normothermia (37 degrees C) was maintained for 1 h after completion of the ischemic challenge. Isoflurane anesthesia was maintained during this period. Five of 15 normothermic rats and 3 of 15 hypothermic rats died of stroke after ischemia. For all rats tested, hypothermic-treated animals had a significantly better neurologic outcome than normothermic rats (p less than 0.05). Histopathology showed a correlation of r = 0.67 (p less than 0.05) with neurologic outcome, and neuronal damage was significantly worse in normothermic compared with hypothermic rats (p less than 0.05). These results show that postischemic hypothermia will decrease neuronal injury and improve neurologic outcome associated with incomplete ischemia.

Hypothermia Versus Ethanol

We examined neurologic outcome after incomplete cerebral ischemia in rats treated with hypothermia versus ethanol, two techniques that decrease brain metabolism. All animals, including control rats, received a baseline midazolam anesthetic. Ischemia was produced by right carotid artery occlusion combined with hemorrhagic hypotension to a mean arterial pressure of 30 mm Hg for 30 min. Neurologic outcome was evaluated for 3 days after ischemia using a 5-point scale. In separate studies, cerebral blood flow (CBF) was measured using radioactive microspheres, and cortical oxygen consumption (CMRO2) was calculated from the blood flow data and the arteriovenous oxygen difference. Hypothermia to 31 degrees C decreased CBF 50% and CMRO2 52% compared with control rats, and significantly improved outcome. Although ethanol decreased CBF 35% and CMRO2 22%, it did not improve outcome from stroke compared with control rats. These results suggest that hypothermia protects the brain from ischemia and that ethanol does not, despite a decrease in CMRO2.

Brain Lactate and Neurologic Outcome Following Incomplete Ischemia in Fasted, Nonfasted, and Glucose-loaded Rats

The neurologic outcomes following incomplete cerebral ischemia in rats treated by fasting, nonfasting, or glucose administration (6 ml/kg of 50% glucose solution intraperitoneal) were compared. Rats were anesthetized with 1.4% inspired isoflurane in air and incomplete ischemia was produced by temporary unilateral carotid occlusion and hypotension of 30 mmHg for 30 min. The rats were recovered and neurologic outcome was scored every 8 h for 3 days using a 6-point scale ranging from 0 (normal) to 5 (death associated with stroke). Brain histopathology was scored using a four-point scale on 19 of 30 rats surviving the 3-day postischemic neurologic examination and was correlated with neurologic deficit scores. Fasted rats had plasma glucose concentrations of 79 +/- 7 mg/100 ml (mean +/- SE) during ischemia and a significantly better neurologic outcome (P less than 0.001) than glucose-loaded rats (plasma glucose = 496 +/- 43 mg/100 ml). Nonfasted rats had blood glucose values (292 +/- 28 mg/100 ml) and deficit scores not significantly different from fasted but better than glucose-loaded rats (P = 0.054). Brain histology showed the greatest neuronal damage in caudate followed by hippocampus and cortical tissue. Histopathologic evaluation showed a correlation of r = 0.87 (P less than 0.01) with neurologic outcome. In separate experiments brain samples were collected at the end of the ischemic period in each of the experimental groups and regional tissue lactate and brain phosphocreatine and adenosinetriphosphate (ATP) concentrations were measured. Ischemic tissue lactate was similar in fasted, nonfasted, and glucose-loaded rats in caudate and hippocampus but was significantly higher in glucose loaded rats in cortical and thalamic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of isoflurane and nitrous oxide on cerebral blood flow, metabolism and electrocorticogram after incomplete cerebral ischemia in the rat

Differential effects of isoflurane (ISOF) and N2O on cerebral blood flow, metabolism and electrocorticogram (ECoG) were examined in rats subjected to 15 min-incomplete cerebral ischemia. In the first study, regional cerebral blood flow (rCBF) and ECoG were measured during and after ischemia. In the second study, local cerebral blood flow (LCBF) and glucose utilization (LCGU) were determined at 60 min after reperfusion. In the N2O group, rCBF in both the cerebral cortex and hippocampus decreased significantly to less than 10% of the pre-ischemic value during ischemia, and it increased to 170% at 10 min after reperfusion. The ECoG became flat during ischemia and reappeared at 21 min after reperfusion. In the ISOF group, rCBF decreased significantly to 25% during ischemia and returned to the preischemic value after reperfusion. The ECoG became flat during ischemia and reappeared at 14 min. In the N2O group, LCBFs decreased significantly to 40-50% of the pre-ischemic values in the forebrain. LCGUs decreased significantly to 30-50% in all structures of the forebrain. In the ISOF group, LCBFs decreased significantly to 60-80% in the forebrain, but were not different in other structures. LCGUs did not differ from pre-ischemic values in all structures except for in the thalamus and habenula. These results may indicate cerebral protective effects of ISOF on incomplete cerebral ischemia in rats.