Neuroprotective effects of preischemia intraarterial magnesium sulfate in reversible focal cerebral ischemia

1996 ◽  
Vol 85 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Marin B. Marinov ◽  
Kimberly S. Harbaugh ◽  
P. Jack Hoopes ◽  
Harold J. Pikus ◽  
Robert E. Harbaugh
Keyword(s):  
Infarct Size ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Suture Technique ◽  
Neuroprotective Effects ◽  
Tetrazolium Chloride ◽  
Content Type ◽  
Fine Print

✓ The known cytoprotective properties of MgSO4 led the authors to study its effects on infarct size in rats when administered intraarterially before reversible focal ischemia. Following an intracarotid infusion of MgSO4 in the amount of 30 mg/kg (24 animals), 90 mg/kg (18 animals), or an equal volume of vehicle (23 animals), middle cerebral artery occlusion was produced in rats by means of an intraluminal suture technique. Reperfusion occurred after 1.5 (42 animals) or 2 hours (23 animals) of ischemia. Automated, volumetric measurements of 2′,3′,5′-triphenyl-2H-tetrazolium chloride—stained coronal brain sections demonstrated a statistically significant decrease in infarct size for MgSO4 treatment groups compared to controls. Cytoprotection was greater in animals subjected to 1.5 hours of ischemia (28.4% reduction in infarct volume, p ≤ 0.001, Student's t-test), than in those having 2 hours of ischemia (19.3% reduction, p < 0.05). Animals given 90 mg/kg MgSO4 prior to 1.5 hours of ischemia (12 animals) showed a 59.8% reduction in infarct volume compared to controls (11 animals, p < 0.001) and a 43.1% reduction compared to the 30 mg/kg group (11 animals, p < 0.001). Analysis of variance demonstrated the statistically significant effects of MgSO4 doses on infarct volume across all groups (F = 22.95, p < 0.0001). The neuroprotective effect of intraarterial MgSO4 in this model is robust, dose dependent, and related to the duration of ischemia. The compound may be valuable for limiting infarction if given intraarterially before induction of reversible ischemia during cerebrovascular surgery.

Proximal occlusion of the middle cerebral artery in C57Black6 mice: relationship of patency of the posterior communicating artery, infarct evolution, and animal survival

2004 ◽  
Vol 100 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Kazuhide Furuya ◽  
Nobutaka Kawahara ◽  
Kensuke Kawai ◽  
Tomikatsu Toyoda ◽  
Keiichiro Maeda ◽  
...  
Keyword(s):  
Survival Rate ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Posterior Communicating Artery ◽  
Neurological Deficits ◽  
Content Type ◽  
Fine Print

Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at 1 week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be circumvented. Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After 1 hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1- and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%. Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.

Use of mild intraischemic hypothermia versus mannitol to reduce infarct size after temporary middle cerebral artery occlusion in rats

1995 ◽  
Vol 83 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Hiroshi Karibe ◽  
Gregory J. Zarow ◽  
Philip R. Weinstein
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Content Type ◽  
Infarct Area ◽  
Group A ◽  
Group B ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ To determine which of two treatments for reducing ischemic injury after temporal focal ischemia is more effective, the effects of mild (33°C) intraischemic hypothermia were compared with those of mannitol, the most commonly used neuroprotective agent. Four groups of Sprague-Dawley rats underwent 1 hour of endovascular middle cerebral artery occlusion followed by 23 hours of normothermic reperfusion. The four experimental groups were as follows: Group A, saline control; Group B, mannitol (25%, 1 g/kg); Group C, hypothermia; and Group D, hypothermia plus man-nitol. Laser-Doppler estimates of cortical blood flow showed that hypothermia did not affect blood flow during ischemia or reperfusion. Mannitol increased cortical blood flow during ischemia and reperfusion under both normothermic and hypothermic conditions (p < 0.05). Neurological deficit was significantly less severe in treated rats (Group B, p < 0.05; Group C or D, p < 0.01) than in controls (Group A). Infarct volume, measured on semiserial Nissl-stained sections, was significantly smaller in treated rats (p < 0.01) than in controls. Infarct volume was also significantly smaller in rats treated with hypothermia than in those treated with mannitol (Group C vs. Group B, p < 0.05); there was no difference between rats treated with mannitol and those treated with mannitol and hypothermia. All three treatments reduced infarct area in the ischemic penumbra; hypothermia with or without mannitol also reduced infarct area in the ischemic core. These results demonstrate that both mild intraischemic hypothermia and mannitol reduce infarct size and neurological deficit: hypothermia reduces infarct size more effectively than mannitol, and mannitol adds no significant protection to hypothermia, whereas hypothermia adds significant protection beyond that afforded by mannitol after brief focal ischemia followed by reperfusion in rats. The results suggest that mild intraischemic hypothermia alone, or in combination with mannitol, may be useful in avoiding ischemic injury from temporary vessel occlusion during cerebrovascular surgery.

Reduced brain infarct volume and improved neurological outcome by inhibition of the NR2B subunit of NMDA receptors by using CP101, 606-27 alone and in combination with rt-PA in a thromboembolic stroke model in rats

2003 ◽  
Vol 98 (2) ◽  
pp. 397-403 ◽  
Author(s):  
Yi Yang ◽  
Qiu Li ◽  
Tao Yang ◽  
Munawar Hussain ◽  
Ashfaq Shuaib
Keyword(s):  
Low Dose ◽  
Seizure Activity ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
High Dose ◽  
Brain Infarct ◽  
Content Type ◽  
Dose Combination ◽  
Fine Print

Object. A novel postsynaptic antagonist of N-methyl-d-aspartate (NMDA) receptors, CP-101,606-27 may attenuate the effects of focal ischemia. In current experiments, the authors investigated its neuroprotective effect alone and in combination with recombinant tissue plasminogen activator (rt-PA) in thromboembolic focal cerebral ischemia in rats. Methods. Forty-eight male Wistar rats underwent embolization of the right middle cerebral artery to produce focal cerebral ischemia. After random division into six groups (eight rats in each group), animals received: vehicle; low-dose (LD) CP-101,606-27, 14.4 mg/kg; high-dose (HD) CP-101,606-27, 28.8 mg/kg; rt-PA, 10 mg/kg; low-dose combination (LDC) CP-101,606-27, 14.4 mg/kg plus rt-PA, 10 mg/kg; or high-dose combination (HDC) CP-101,606-27, 28.8 mg/kg plus rt-PA, 10 mg/kg) 2 hours after induction of embolic stroke. Animals were killed 48 hours after the onset of focal ischemia. Brain infarction volume, neurobehavioral outcome, poststroke seizure activity, poststroke mortality, and intracranial hemorrhage incidence were observed and evaluated. Compared with vehicle-treated animals (39.4 ± 8.6%) 2 hours posttreatment with CP-101,606-27 or rt-PA or in combination a significant reduction in the percentage of brain infarct volume was seen (LD CP-101,606-27: 20.8 ± 14.3%, p < 0.05; HD CP-101,606-27: 10.9 ± 3.2%, p < 0.001; rt-PA: 21.1 ± 7.3%, p < 0.05; LDC, 18.6 ± 11.5%, p < 0.05; and HDC: 15.2 ± 10.1%, p < 0.05; compared with control: 39.4 ± 8.6%). Combination of CP-101,606-27 with rt-PA did not show a significantly enhanced neuroprotective effect. Except for the control and LDC treatment groups, neurobehavioral outcome was significantly improved 24 hours after embolic stroke in animals in all other active therapeutic groups receiving CP-101,606-27 or rt-PA or in combination. The authors also observed that treatment with HD CP-101,606-27 decreased poststroke seizure activity. Conclusions. The data in this study suggested that postischemia treatment with CP-101,606-27 is neuroprotective in the current stroke model; however, the authors also note that although rt-PA may offer modest protection when used alone, combination with CP-101,606-27 did not appear to enhance its effects.

scholarly journals Expression of HSP70 in cerebral ischemia and neuroprotetive action of hypothermia and ketoprofen

2010 ◽  
Vol 68 (4) ◽  
pp. 592-596 ◽  
Author(s):  
Daniela Pretti da Cunha Tirapelli ◽  
Carlos Gilberto Carlotti Junior ◽  
João Pereira Leite ◽  
Luis Fernando Tirapelli ◽  
Benedicto Oscar Colli
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Hsp70 Expression ◽  
Tetrazolium Chloride ◽  
A Cell ◽  
Shock Proteins ◽  
H Protein

Heat shock proteins (HSPs) are molecular chaperones that bind to other proteins to shepherd them across membranes and direct them to specific locations within a cell. Several injurious stimuli can induce Hsp70 expression, including ischemia. This study aimed to investigate the pattern of expression of protein (immunohistochemistry) and gene (real-time PCR) Hsp70 in experimental focal cerebral ischemia in rats by occlusion of the middle cerebral artery for 1 hour and the role of neuroprotection with hypothermia (H) and ketoprofen (K). The infarct volume was measured using morphometric analysis defined by triphenyl tetrazolium chloride. It was observed increases in the protein (p=0.0001) and gene (p=0.0001) Hsp70 receptor in the ischemic areas that were reduced by H (protein and gene: p<0.05), K (protein: p<0.001), and H+K (protein: p<0.01 and gene: p<0.05). The Hsp70 increases in the ischemic area suggests that the Hsp70-mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, H and K are directly involved with the Hsp70.

Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1085-1093 ◽  
Author(s):  
E-Jian Lee ◽  
Ming-Yang Lee ◽  
Guan-Liang Chang ◽  
Li-Hsuan Chen ◽  
Yu-Ling Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Content Type ◽  
Delayed Treatment ◽  
Cerebral Ischemia Reperfusion ◽  
Fine Print

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion. Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died. Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively. Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.

scholarly journals Intraventricular Brain-Derived Neurotrophic Factor Reduces Infarct Size after Focal Cerebral Ischemia in Rats

1997 ◽  
Vol 17 (5) ◽  
pp. 500-506 ◽  
Author(s):  
Wolf-R. Schäbitz ◽  
Stefan Schwab ◽  
Matthias Spranger ◽  
Werner Hacke
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Neurotrophic Factor ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 μg/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls ( P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 ± 27.1 mm3 in BDNF-treated animals and 139.2 ± 56.4 mm3 in controls (mean ± SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 ± 7.1 mm3 in BDNF-treated animals and 37.9 ± 19.8 mm3 in controls (mean ± SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats

1985 ◽  
Vol 62 (6) ◽  
pp. 874-881 ◽  
Author(s):  
Robert J. Dempsey ◽  
Mark W. Roy ◽  
Kathleen L. Meyer ◽  
David L. Donaldson
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Opposite Hemisphere ◽  
Content Type ◽  
Beneficial Effects ◽  
Cerebral Artery Occlusion ◽  
Fine Print

✓ Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p < 0.05). This was noted in densely ischemic areas (indomethacin = 84.3%, control = 87.5%), in “penumbra” regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p < 0.05), as was cerebral perfusion (p < 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p < 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p < 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbitalstabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.

Down-Regulation of Nogo-A and PirB in Ischemic Cortex with Remote Ischemic Preconditioning in Mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiao Y ◽  
◽  
Wang J ◽  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Remote Ischemic Preconditioning ◽  
Tetrazolium Chloride ◽  
Hematoxylin And Eosin ◽  
Cerebral Artery Occlusion

Objectives: The present study aims to investigate the effect of Limb Remote Ischemic Preconditioning (LRIP) on the expression of Nogo-A and PirB in the cortex of mice with focal cerebral ischemia, and related pathways involving in axonal regeneration and neurological function recovery after cerebral ischemia. Methods: Adult male C57/BL6 mice were divided into sham-operated (sham), transient Middle Cerebral Artery Occlusion (MCAO), LRIP and anti- PirBAb treatment group. Samples were collected 48h after cerebral ischemia. The histopathologic changes were assessed by 1,3,5-Triphenyl-2H-Tetrazolium Chloride (TTC), and Hematoxylin and Eosin (HE) staining and TUNEL method. The expression of Nogo-A and PirB were determined by immunofluorescence, RT-PCR and Western blot respectively. Results: TTC staining showed that LRIP treatment reduced the infarct size of mice and anti-PirBAb treatment further decline the infarct size, which was accompanied with the decline of neurological deficit score and reduction of neuronal damage. LRIP treatment also reduced the TUNEL positive cells induced by MCAO and anti-PirBAb treatment further strengthened the effect of LRIP. Except sham group, the expressions of Nogo-A and PirB in other three groups all increased with varying degrees, among which MCAO group was the highest, LRIP group was the second and the anti-PirBAb group was the lowest. The expressions of growth associated protein 43 (GAP43) showed opposite tendency. Conclusions: LRIP plays beneficial influence on cerebral ischemia. LRIP and PirB inhibition combination has a better protective effect on nervous system after cerebral ischemia in mice.

Abstract TP84: Comparative Analysis of Genetic and Pharmacological Inhibition of Sirt3 in Post Ischemic Injury

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rajkumar Verma ◽  
Rodney Ritzel ◽  
Bruce Liang ◽  
Louise McCullough
Keyword(s):  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Pharmacological Study ◽  
Ischemic Injury ◽  
Target Protein ◽  
Cns Injury ◽  
Neuroprotective Effects ◽  
Pharmacological Inhibition

Background: Sirtuin3 (Sirt3), NAD+-dependent deacetylase, regulates several key proteins in both mitochondria and nucleus. The majority of early studies have shown neuroprotective effects of Sirt3 activation in various models of CNS injury. Recently, it was found that genetic loss of Sirt3 is beneficial in ischemia/reperfusion (I/R) injury. Therefore, this study was designed to explore the effects of both genetic and pharmacological inhibition of Sirt3 in a middle cerebral artery occlusion (MCAo) model of stroke. Methods: Focal cerebral ischemia was induced by transient right MCAo for 60min followed by 0, 6, 24 and 72 hrs of reperfusion. A 72hrs post ischemic injury time point was chosen to measure infarction in various treatment groups. The Sirt3 inhibitor AGK7 (sc- 204281 Santa cruz,) that selectively inhibits Sirt3 over Sirt1 and Sirt2, was given as single intraperitoneal injection (0.15, 0.5 and 1.5mg/kg) 3hrs after stroke onset. Activity or expression of Sirt3, was examined with Sirt3 activity kit or western blot using anti-Sirt3, anti-acetylated lysine antibodies. Results: Sirt3 knockout mice showed a significant reduction in hemispheric infarct volume compared to WT littermate controls (37.72±5.21 vs 52.8±6.76, p<0.05). In the pharmacological study, a dose of 0.5 mg/kg i.p of inhibitor showed significant reduction in Sirt3 activity and but had no neuroprotective effect. Furthermore, a much higher dose (1.5mg/kg i.p) did not show any additional inhibitory effect on sirt3 activity but unexpectedly increased infarct volume (51.8±6.87 vs. 62.56± 7.89, P<0.05) and hemorrhagic transformation. Expression studies showed no overall change in Sirt3 expression in whole cell lysates at 0, 6, 24 or 72 hrs after reperfusion; however the expression pattern and activity varied with time in different subcellular compartments. Summary and Conclusions: Changes in subcellular translocation and activity of Sirt3 after I/R stress suggests it important role in target protein deacetylation in stroke pathophysiology. Surprisingly, genetic deletion but not pharmacological inhibition led to neuroprotection, indicating the need to carefully examine target protein by both genetic and pharmacological approaches.

Effect of intermittent reperfusion and nitric oxide synthase inhibition on infarct volume during reversible focal cerebral ischemia

1995 ◽  
Vol 83 (3) ◽  
pp. 491-495 ◽  
Author(s):  
Brian A. Iuliano ◽  
Robert E. Anderson ◽  
Fredric B. Meyer
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Vascular Occlusion ◽  
Artery Occlusion ◽  
Content Type ◽  
Infarction Size ◽  
Oxide Synthase

✓ The authors examined the effects of both intermittent reperfusion and nitric oxide synthase (NOS) inhibition, caused by NG-nitro-l-arginine methyl ester (l-NAME) during episodes of focal cerebral ischemia induced to simulate the neurosurgical setting. Seventy-eight Wistar rats underwent single (60 minutes of ischemia) or repetitive (four 15-minute periods of ischemia separated by 5 minutes of reperfusion) episodes of middle cerebral artery occlusion while under anesthesia (1.0% halothane). Twenty-four hours after the procedure, the animals were given neurological examinations and then sacrificed for histological preparation and examination. The intermittent reperfusion groups tended to have smaller mean cortical infarctions. There was also a trend showing a decrease in infarction size in groups given l-NAME. The combination of intermittent reperfusion and preischemic administration ofl-NAME (10 mg/kg) resulted in a 65% reduction in infarction size (p < 0.05) when compared to that caused by 60 minutes of single occlusion without l-NAME. The use of NOS inhibition combined with intermittent reperfusion may be a technique to provide intraoperative cerebral protection during neurovascular procedures that require temporary vascular occlusion.

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