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.

Inhibition of inducible nitric oxide synthase ameliorates cerebral ischemic damage

1995 ◽  
Vol 268 (1) ◽  
pp. R286-R292 ◽  
Author(s):  
C. Iadecola ◽  
F. Zhang ◽  
X. Xu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Oxide Synthase

We sought to determine whether expression of the inducible, calcium-independent isoform of nitric oxide synthase (iNOS) contributes to the tissue damage produced by focal cerebral ischemia. The middle cerebral artery was occluded in halothane-anesthetized spontaneously hypertensive rats. Twenty-four hours later rats received intraperitoneal injections of the iNOS inhibitor aminoguanidine (100 mg/kg twice per day; n = 10) or of aminoguanidine + L-arginine (300 mg/kg four times per day; n = 7), aminoguanidine + D-arginine (n = 7), arginine alone (n = 6), or vehicle (n = 9). Drugs were administered for 3 consecutive days. Infarct volume was determined by image analysis in thionin-stained brain sections 4 days after induction of ischemia. Administration of aminoguanidine reduced infarct volume by 33 +/- 4% (P < 0.05 from vehicle; analysis of variance and Tukey's test), a reduction that was antagonized by coadministration of L- but not D-arginine. Administration of L-arginine alone did not affect infarct size (P > 0.05 vs. vehicle). In separate rats (n = 10), aminoguanidine attenuated calcium-independent NOS activity in the infarct (P < 0.05 vs. vehicle) without affecting calcium-dependent activity (P > 0.05). Aminoguanidine did not affect resting cerebral blood flow or the cerebrovascular vasodilation elicited by hypercapnia, as determined by laser-Doppler flowmetry (n = 4). We conclude that aminoguanidine selectively inhibits iNOS activity in the area of infarction and reduces the volume of the infarct produced by middle cerebral artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The effect of nitric oxide synthase inhibition on infarct volume after reversible focal cerebral ischemia in conscious rats.

Stroke ◽  
1993 ◽  
Vol 24 (12) ◽  
pp. 2023-2029 ◽  
Author(s):  
J W Kuluz ◽  
R J Prado ◽  
W D Dietrich ◽  
C L Schleien ◽  
B D Watson
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Conscious Rats ◽  
Oxide Synthase

scholarly journals Time Dependence of Effect of Nitric Oxide Synthase Inhibition on Cerebral Ischemic Damage

1995 ◽  
Vol 15 (4) ◽  
pp. 595-601 ◽  
Author(s):  
Fangyi Zhang ◽  
Sherry Xu ◽  
Costantino Iadecola
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemic Damage ◽  
Nitric Oxide Synthesis ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage ◽  
Oxide Synthase

Nitric oxide, a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia as it may facilitate collateral blood flow to the ischemic territory. Accordingly, the effect of inhibition of nitric oxide synthesis on cerebral ischemic damage may vary depending on the timing of the inhibition relative to the induction of ischemia. We therefore studied the time course of the effect of nitric oxide synthesis inhibition on focal cerebral ischemic damage. The middle cerebral artery was permanently occluded in spontaneously hypertensive rats and the nitric oxide synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) was administered systemically (3 mg/kg) <5 min or 2, 3, or 6 h later. Arterial pressure, rectal temperature, plasma glucose, and hematocrit were monitored. Infarct volume was determined on thioninstained sections 24 h after induction of ischemia. NOS activity was determined in cerebellum from the conversion of l-[3H]arginine to l-[3H]citrulline. Administration of l-NAME <5 min after arterial occlusion increased the infarct volume by 23 ± 14% (mean ± SD; p < 0.05, analysis of variance), while administration of l-NAME at 2 or 6 h did not affect the size of the infarct (p > 0.05). l-NAME administration 3 h after induction of ischemia reduced neocortical infarct size by 14 ± 11% (p < 0.05). l-NAME decreased cerebellar NOS activity comparably in all groups (range 16–25%). We conclude that the effects of inhibition of nitric oxide synthesis on focal cerebral ischemic damage are time dependent. Thus, inhibition of nitric oxide synthesis worsens ischemic damage when instituted shortly after induction of ischemia and does not affect or reduces damage at later times. The results support the hypothesis that the vascular actions of nitric oxide are beneficial only in the early stages of permanent focal cerebral ischemia.

Effects of Inhibition of Nitric Oxide Synthase on Blood-Brain Barrier Transport in Focal Cerebral Ischemia

Pharmacology ◽  
1994 ◽  
Vol 48 (6) ◽  
pp. 367-373 ◽  
Author(s):  
Oak Za Chi ◽  
Hwu Meei Wei ◽  
Arabinda K. Sinha ◽  
Harvey R. Weiss
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Blood Brain Barrier ◽  
Focal Cerebral Ischemia ◽  
Brain Barrier ◽  
Blood Brain ◽  
Oxide Synthase

Effect of focal cerebral ischemia on nitric oxide synthase expression in rats

1997 ◽  
Vol 30 (2) ◽  
pp. 55-62 ◽  
Author(s):  
Hideki Homma ◽  
Hidekatsu Mizushima ◽  
Yoshinori Arai ◽  
Kenji Dohi ◽  
Kiyoshi Matsumoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Oxide Synthase

scholarly journals Functional Deterioration of Endothelial Nitric Oxide Synthase after Focal Cerebral Ischemia

2013 ◽  
Vol 33 (10) ◽  
pp. 1532-1539 ◽  
Author(s):  
Yoshiki Yagita ◽  
Kazuo Kitagawa ◽  
Naoki Oyama ◽  
Toshiro Yukami ◽  
Akihiro Watanabe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Focal Cerebral Ischemia ◽  
Rho Kinase ◽  
Ischemic Lesion ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Functional Deterioration

Endothelial nitric oxide synthase (eNOS) dysfunction is related to secondary injury and lesion expansion after cerebral ischemia. To date, there are few reports about postischemic alterations in the eNOS regulatory system. The purpose of the present study was to clarify eNOS expression, Ser1177 phosphorylation, and monomer formation after cerebral ischemia. Male Wistar rats were subjected to transient focal cerebral ischemia. Endothelial nitric oxide synthase messenger RNA (mRNA) and protein expression increased ~ 8-fold in the ischemic lesion. In the middle cerebral artery core, eNOS-Ser1177 phosphorylation increased 6 hours after ischemia; however, there was an approximately 90% decrease in eNOS-Ser1177 phosphorylation observed 24 hours after ischemia that continued until at least 7 days after ischemia. Endothelial nitric oxide synthase monomer formation also increased 24 and 48 hours after ischemia ( P<0.05), and protein nitration progressed in parallel with monomerization. To assess the effect of a neuroprotective agent on eNOS dysfunction, we evaluated the effect of fasudil, a Rho-kinase inhibitor, on eNOS phosphorylation and dimerization. Postischemic treatment with fasudil suppressed lesion expansion and dephosphorylation and monomer formation of eNOS. In conclusion, functional deterioration of eNOS progressed after cerebral ischemia. Rho-kinase inhibitors can reduce ischemic lesion expansion as well as eNOS dysfunction in the ischemic brain.

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