scholarly journals Systemic Nitric Oxide Synthase Inhibition Does Not Affect Brain Oxygenation during Cortical Spreading Depression in Rats: A Noninvasive Near-Infrared Spectroscopy and Laser-Doppler Flowmetry Study

1996 ◽  
Vol 16 (6) ◽  
pp. 1100-1107 ◽  
Author(s):  
Tilo Wolf ◽  
Ute Lindauer ◽  
Hellmuth Obrig ◽  
Jens Dreier ◽  
Tobias Back ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Infrared Spectroscopy ◽  
Nitric Oxide Synthase ◽  
Near Infrared Spectroscopy ◽  
Laser Doppler Flowmetry ◽  
Cortical Spreading Depression ◽  
Near Infrared ◽  
Spreading Depression ◽  
Doppler Flowmetry ◽  
Oxide Synthase

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200–400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state Polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3, warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N′-nitro-l-arginine had no significant effect on the perfusion response or the tissue Po2 during CSD. During most CSD episodes, a brief decrease in MABP by 4–8 mm Hg was noted that might be caused by functional decortication during CSD.

scholarly journals Endothelial Nitric Oxide Synthase-Dependent Cerebral Blood Flow Augmentation by L-Arginine After Chronic Statin Treatment

2000 ◽  
Vol 20 (4) ◽  
pp. 709-717 ◽  
Author(s):  
Masaru Yamada ◽  
Zhihong Huang ◽  
Turgay Dalkara ◽  
Matthias Endres ◽  
Ulrich Laufs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Laser Doppler Flowmetry ◽  
Brain Blood Flow ◽  
Arginine Infusion ◽  
Doppler Flowmetry ◽  
Ischemic Brain ◽  
Oxide Synthase

Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by 14C-iodoamphetamine indicator fractionation or 14C-iodoantipyrine tissue equilibration techniques. rCBF increased by 26% (laser Doppler flowmetry) after L-arginine infusion but did not change in mutant mice deficient in eNOS expression. After eNOS upregulation by chronic simvastatin treatment (2 mg/kg subcutaneously, daily for 14 days), L-arginine amplified and sustained the hyperemia (38%) and increased absolute brain blood flow from 86 ± 7 to 119 ± 10 mL/100 g per minute. Furthermore, pretreatment with simvastatin enhanced blood flow within ischemic brain tissue after middle cerebral artery occlusion. Together, these findings suggest that eNOS activity is critical for blood flow augmentation during acute L-arginine infusion, and chronic eNOS upregulation combined with L-arginine administration provides a novel strategy to elevate cerebral blood flow in the normal and ischemic brain.

NOS activity in brain and endothelium: relation to hypercapnic rise of cerebral blood flow in rats

1996 ◽  
Vol 271 (5) ◽  
pp. H2035-H2044 ◽  
Author(s):  
M. Fabricius ◽  
I. Rubin ◽  
M. Bundgaard ◽  
M. Lauritzen
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nitric Oxide Synthase ◽  
Cerebellar Cortex ◽  
Laser Doppler Flowmetry ◽  
Doppler Flowmetry ◽  
Nos Inhibitor ◽  
Neuronal Nos ◽  
Oxide Synthase

We examined whether attenuation of the hypercapnic increase of cerebral blood flow (CBF) associated with nitric oxide synthase (NOS) inhibition is related to local neuronal or aortic endothelial NOS activity or local endothelial/neuronal NOS-dependent vasodilation. Halothane-anesthetized rats were ventilated, and CBF was measured by laser-Doppler flowmetry over the parietal and cerebellar cortex. Intravenous N omega-nitro-L-arginine (L-NNA; 30 mg/kg) inhibited brain and aortic NOS activity by 67-70%. Topical L-NNA (1 mM) inhibited brain NOS activity by 91-94%, whereas aortic NOS activity remained constant. In contrast, intravenous L-NNA attenuated the hypercapnic CBF rise much more efficiently than topical L-NNA. 7-Nitroindazole, another NOS inhibitor, attenuated endothelial and neuronal NOS activity equally well and inhibited the hypercapnic CBF increase as effectively as L-NNA. Topical L-NNA and 7-nitroindazole abolished local endothelial NOS-dependent vasodilation after 15 min, whereas hypercapnic CBF was only slightly reduced. L-NNA injected into the tissue abolished neuronal NOS-dependent vasodilation, whereas hypercapnic CBF was unchanged. The findings suggest that local NOS activity, whether neuronal or endothelial, is unimportant for the hypercapnic rise of CBF.

Monitoring cerebral perfusion using near-infrared spectroscopy and laser Doppler flowmetry

2003 ◽  
Vol 24 (4) ◽  
pp. N35-N40 ◽  
Author(s):  
J H G M Klaessens ◽  
R G M Kolkman ◽  
J C W Hopman ◽  
E Hondebrink ◽  
K D Liem ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Laser Doppler Flowmetry ◽  
Cerebral Perfusion ◽  
Near Infrared ◽  
Laser Doppler ◽  
Doppler Flowmetry

scholarly journals Nitric Oxide Scavenging by Hemoglobin or Nitric Oxide Synthase Inhibition by N-Nitro-L-Arginine Induces Cortical Spreading Ischemia When K+ Is Increased in the Subarachnoid Space

1998 ◽  
Vol 18 (9) ◽  
pp. 978-990 ◽  
Author(s):  
Jens P. Dreier ◽  
Katrin Körner ◽  
Nathalie Ebert ◽  
Astrid Görner ◽  
Inger Rubin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Transient Ischemia ◽  
Cranial Window ◽  
Radical Production ◽  
Oxide Synthase ◽  
Ischemic Events

We investigated the combined effect of increased brain topical K+ concentration and reduction of the nitric oxide(NO.) level caused by nitric oxide scavenging or nitric oxide synthase (NOS) inhibition on regional cerebral blood flow and subarachnoid direct current (DC) potential. Using thiopental-anesthetized male Wistar rats with a closed cranial window preparation, brain topical superfusion of a combination of the NO. scavenger hemoglobin(Hb; 2 mmol/L) and increased K+ concentration in the artificial cerebrospinal fluid ([K+]ACSF) at 35 mmol/L led to sudden spontaneous transient ischemic events with a decrease of CBF to 14 ± 7% (n = 4) compared with the baseline (100%). The ischemic events lasted for 53 ± 17 minutes and were associated with a negative subarachnoid DC shift of −7.3 ± 0.6 mV of 49 ± 12 minutes' duration. The combination of the NOS inhibitor N-nitro-L-arginine(L-NA, 1 mmol/L) with [K+]ACSF at 35 mmol/L caused similar spontaneous transient ischemic events in 13 rats. When cortical spreading depression was induced by KCl at a 5-mm distance, a typical cortical spreading hyperemia (CSH) and negative DC shift were measured at the closed cranial window during brain topical superfusion with either physiologic artificial CSF (n = 5), or artificial CSF containing increased [K+]ACSF at 20 mmol/L (n = 4), [K+]ACSF at 3 mmol/L combined with L-NA (n = 10), [K+]ACSF at 10 mmol/L combined with L-NA (five of six animals) or [K+]ACSF at 3 mmol/L combined with Hb (three of four animals). Cortical spreading depression induced long-lasting transient ischemia instead of CSH, when brain was superfused with either[K+]ACSF at 20 mmol/L combined with Hb (CBF decrease to 20± 20% duration 25 ± 21 minutes, n = 4), or [K+]ACSF at 20 mmol/L combined with L-NA (n = 19). Transient ischemia induced by NOS inhibition and [K+]ACSF at 20 mmol/L propagated at a speed of 3.4 ± 0.6 mm/min, indicating cortical spreading ischemia (CSI). Although CSH did not change oxygen free radical production, as measured on-line by in vivo lucigenin-enhanced chemiluminescence, CSI resulted in the typical radical production pattern of ischemia and reperfusion suggestive of brain damage (n = 4). Nimodipine (2 μg/kg body weight/min intravenously) transformed CSI back to CSH (n = 4). Vehicle had no effect on CSI(n = 4). Our data suggest that the combination of decreased NO. levels and increased subarachnoid K+ levels induces spreading depression with acute ischemic CBF response. Thus, a disturbed coupling of metabolism and CBF can cause ischemia. We speculate that CSI may be related to delayed ischemic deficits after subarachnoid hemorrhage, a clinical condition in which the release of Hb and K+ from erythrocytes creates a microenvironment similar to the one investigated here.

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