scholarly journals Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hock-Kean Liew ◽  
Jon-Son Kuo ◽  
Jia-Yi Wang ◽  
Cheng-Yoong Pang
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Infarct Volume ◽  
Neurological Deficits ◽  
No Production ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Regional Cerebral Blood ◽  
Rapid Reduction ◽  
Stimulating Factor

Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-NG-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury.

Regional cerebral blood flow and metabolism in reversible ischemia due to vasospasm

1985 ◽  
Vol 62 (4) ◽  
pp. 539-546 ◽  
Author(s):  
William J. Powers ◽  
Robert L. Grubb ◽  
Roy P. Baker ◽  
Mark A. Mintun ◽  
Marcus E. Raichle
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Emission Tomography ◽  
Neurological Deficits ◽  
Regional Cerebral Blood ◽  
Content Type ◽  
Cerebral Metabolic Rate ◽  
Positron Emission ◽  
Reversible Ischemia

✓ Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) were measured by positron emission tomography (PET) in four patients with subarachnoid hemorrhage and hemiparesis due to cerebral vasospasm. With resolution of the vasospasm, two patients recovered and two remained hemiparetic. Contralateral to the hemiparesis, rCBF was slightly higher in the two patients who eventually recovered (15.0 and 16.2 ml/100 gm/min) than in the two who remained hemiparetic (12.0 and 11.7 ml/100 gm/min). The rCMRO2 measurements showed similar differences, with values of 1.34 and 2.60 ml/100 gm/min in the patients who recovered, and 0.72 and 1.66 ml/100 gm/min in those who did not. These preliminary findings indicate that with PET studies it may be possible to prospectively differentiate patients with neurological deficits due to reversible ischemia from patients with irreversible infarction.

Cerebral Blood Flow and Cerebral Metabolic Rate of Oxygen Requirements for Cerebral Function and Viability in Humans

1985 ◽  
Vol 5 (4) ◽  
pp. 600-608 ◽  
Author(s):  
William J. Powers ◽  
Robert L. Grubb ◽  
Danielle Darriet ◽  
Marcus E. Raichle
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Cerebral Blood Volume ◽  
Oxygen Extraction Fraction ◽  
Neurological Deficits ◽  
Regional Cerebral Blood ◽  
Cerebral Tissue ◽  
Cerebral Metabolic Rate ◽  
Regional Cerebral Blood Volume

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.

Regional cerebral blood flow response to vibrissal stimulation in mice lacking type I NOS gene expression

1996 ◽  
Vol 270 (3) ◽  
pp. H1085-H1090 ◽  
Author(s):  
J. Ma ◽  
C. Ayata ◽  
P. L. Huang ◽  
M. C. Fishman ◽  
M. A. Moskowitz
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
No Production ◽  
Type I ◽  
Regional Cerebral Blood ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Whisker Stimulation ◽  
Neuronal Nos

The role of nitric oxide (NO) in cerebral blood flow-metabolism coupling was assessed in SV-129 wild-type (WT) and neuronal (type I) NO synthase (NOS) knockout mice (Kn). Regional cerebral blood flow (rCBF; laser-Doppler flowmetry) was measured over the contralateral cortical barrel field during unilateral mechanical vibrissal deflection (2-3 Hz, 60 s) under urethan anesthesia. The rCBF response was similar in WT and Kn and did not differ when recorded over the intact skull or closed cranial window preparations. Whisker stimulation increased rCBF by 41 +/- 8% (maximum) and 27 +/- 6% (mean) in WT (n = 6) and 41 +/- 7% (maximum) and 26 +/- 6% (mean) in Kn (n = 6) when recorded through a closed cranial window. After superfusion with topical N omega-nitro-L-arginine (L-NNA; 1 mM), the rCBF response was inhibited by approximately 45% in WT mice (P < 0.05), whereas there was no inhibition in Kn. Endothelium-dependent relaxation, assessed by pial vessel dilation in response to topical acetylcholine (100 microM) and inhibition by L-NNA (1 mM), was the same in both groups. Our results suggest that 1) endothelial NO production does not mediate the rCBF coupling to neuronal activity in Kn, 2) the inhibitory effect of L-NNA on the rCBF response to whisker stimulation in WT is a consequence of type I (neuronal) NOS inhibition, and 3) NO-independent mechanisms couple rCBF and metabolism during whisker stimulation in mice lacking expression of neuronal NOS.

scholarly journals G-CSF Reduces Infarct Volume and Improves Functional Outcome after Transient Focal Cerebral Ischemia in Mice

2005 ◽  
Vol 25 (4) ◽  
pp. 431-439 ◽  
Author(s):  
Claire L Gibson ◽  
Philip MW Bath ◽  
Sean P Murphy
Keyword(s):  
Cerebral Ischemia ◽  
Water Maze ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Lesion Volume ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Growth factors possess neuroprotective and neurotrophic properties in vitro, but few have been extensively studied in vivo after stroke. In the present study, we investigated the potential functional benefits of granulocyte colony-stimulating factor (G-CSF) administration after focal cerebral ischemia. Male mice underwent 60-minute middle cerebral artery occlusion (MCAO) and received G-CSF (50 μg/kg, subcutaneously) or vehicle (saline) at the onset of reperfusion. Granulocyte colony-stimulating factor-treated mice killed at 48 hours after MCAO revealed a >45% reduction ( P<0.05) in lesion volume. In terms of body weight recovery, and in tests of motor (grid test and rotarod) and cognitive ability (water maze), MCAO significantly worsened the outcome in vehicle-treated mice as compared with shams ( P<0.05). However, G-CSF treatment was beneficial as, compared with vehicle, this significantly improved weight recovery and motor ability. This effect was most apparent on the water maze where G-CSF-treated mice were indistinguishable from shams in terms of acquiring the task. These results indicate long-term beneficial effects of a single dose of G-CSF administered on reperfusion, and illustrate the need to further investigate the mechanisms of G-CSF action.

Regional cerebral blood flow in patients with ruptured intracranial aneurysms

1979 ◽  
Vol 50 (5) ◽  
pp. 587-594 ◽  
Author(s):  
Ryoji Ishii
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Intracranial Aneurysms ◽  
Vascular Reactivity ◽  
Clinical Severity ◽  
Neurological Deficits ◽  
Intracerebral Hematoma ◽  
Regional Cerebral Blood ◽  
Ruptured Intracranial Aneurysms

✓ Eighty-five studies of regional cerebral blood flow (rCBF) were performed on 49 patients with ruptured intracranial aneurysms. The changes in rCBF were analyzed under various pathophysiological conditions. The degree of flow abnormalities correlated well with the clinical severity of neurological deficits. All of the patients with diffuse vasospasm of severe grade, to less than half of their control value, showed focal areas of decreased flow below 30 ml/100 gm/min, in addition to a reduction in mean CBF. The relief or disappearance of vasospasm in angiograms was followed by the increase of rCBF in the ischemic focus and mean CBF. Marked reduction in rCBF was found in patients with intracerebral hematoma and ventricular dilatation. Impaired CO2 response and autoregulation were found in patients with severe neurological deficits, a severe degree of vasospasm and marked depression of mean CBF. In this series direct operation was delayed in patients with impaired vascular reactivity as well as marked decrease of mean CBF below 30 ml/100 gm/min; good clinical results were obtained in these patients.

scholarly journals Electroacupuncture and Brain Protection against Cerebral Ischemia: Specific Effects of Acupoints

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Fei Zhou ◽  
Jingchun Guo ◽  
Jieshi Cheng ◽  
Gencheng Wu ◽  
Jian Sun ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Neurological Deficit ◽  
Death Rate ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Specific Effects ◽  
Cerebral Artery Occlusion

Electroacupuncture (EA) has been shown to increase cerebral blood flow (CBF) and reduce ischemic infarction in the rat model of cerebral ischemia (middle cerebral artery occlusion, MCAO). Since multiple acupoints are recommended to treat cerebral ischemia, we performed this study to investigate if there is any variation in EA protection against cerebral ischemia with the stimulation of certain “acupoints” in rats. One hour of right MCAO with an 85% reduction of blood flow induced an extensive infarction (32.9% ±3.8% of the brain), serious neurological deficits (scale = 6.0±0.5, on a scale of 0–7), and a 17% (10 out of 60) mortality. EA, with a sparse-dense wave (5 Hz/20 Hz) at 1.0 mA for 30 minutes, at Du 20 and Du 26 greatly reduced the infarction to 4.5% ±1.5% (P<0.01), significantly improved neurological deficit (scale = 1.0±0.5,P<0.01), and decreased the death rate to 7% (2 out of 30,P<0.01). Similarly, EA at left LI 11 & PC 6 reduced the infarct volume to 8.6% ±3.8% (P<0.01), improved the neurological deficit (scale = 2.0±1.0,P<0.01), and decreased the death rate to 8% (2 out of 24,P<0.01). In sharp contrast, EA at right LI 11 & PC 6 did not lead to any significant changes in the infarct volume (33.4% ±6.3%), neurological deficit (scale = 6.5±0.5), and the death rate (20%, 5 out of 24). EA at left GB 34 & SP 6, also had an inconspicuous effect on the ischemic injury. EA at Du 20 & Du 26 or at left LI 11 & PC 6 instantaneously induced a significant increase in cerebral blood flow. Neither EA at right LI 11 & PC 6 nor at GB 34 & SP 6 increased cerebral blood flow. These results revealed that the EA protection against cerebral ischemia is relatively acupoint specific.

Abstract WP133: L-serine Treatment Confers Neuroprotection Against Permanent Focal Cerebral Ischemia In Rats Via Improving Regional Cerebral Blood Flow

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Guohua Wang ◽  
Zhenglin Jiang ◽  
Taojie Ren ◽  
Xia Li ◽  
Yunfeng Zhang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Potassium Channels ◽  
Regional Cerebral Blood Flow ◽  
Neuroprotective Effect ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Regional Cerebral Blood ◽  
Ischemic Brain ◽  
Calcium Activated Potassium Channels

Introduction: L-serine plays critical roles in neuronal development and function. We have recently reported that L-serine protected against ischemic neuronal injury in vivo and in vitro. The mechanism underlying the neuroprotective effect of L-serine remains unclear. L-serine has been documented to induce a fall in mean arterial pressure through activation of small- and intermediate-conductance calcium-activated potassium channels on the endothelium. Such vasodilating action of L-serine in cerebral blood vessels has not been investigated. Hypothesis: Improving regional cerebral blood flow (rCBF) by L-serine contributes to its neuroprotection on the brain after permanent middle cerebral artery occlusion (pMCAO). Methods: Adult male Sprague-Dawley rats were randomly assigned to sham, vehicle or L-serine-treated groups. pMCAO was induced while monitoring rCBF. The neurological deficit scores, brain infarct volumes and physiological parameters were assessed. L-serine and D-serine content in the cortex was measured with high performance liquid chromatography. Results: Compared to vehicle treatment, administration of L-serine improved rCBF in the ischemic cortex and reduced the neurological deficits, infarct volume and cortical neuronal loss in a dose- and time-dependent manner. The improvement of rCBF and neuroprotective effect of L-serine were abolished by apamin plus charybdotoxin, which blocks the calcium-activated potassium channels on the endothelium, but not influenced by strychnine, an antagonist of glycine receptors. HPLC results shows that L-serine treatment increased the content of both L-serine and D-serine in the ischemic cortex. However, inhibiting the conversion of L-serine to D-serine by aminooxyacetic acid did not affect the L-serine-afforded protection, suggesting that the neuroprotective efficacy of L-serine is not related to the conversion of L-serine to D-serine. Conclusions: L-serine displayed a neuroprotective effect in the ischemic brain, at least partly due to an elevation in rCBF through cerebral blood vessel dilation mediated by the calcium-activated potassium channels on the endothelial cells. L-serine may be a potential novel therapy for ischemic brain injury.

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