Monitoring Of Cortical Blood Flow Research Articles

Establishment of transparent cranial window after cerebral subarachnoid hemorrhage and studying of cerebral cortical blood flow in rats

Objective Establishment of a transparent cranial window model of subarachnoid hemorrhage in rats for 7 days of continuous monitoring of cortical blood flow after subarachnoid hemorrhage Methods Thirty SD male rats were randomly divided into normal control group (n=10), saline group (n=10)and blood injection group (n=10). The transcranial subarachnoid hemorrhage transparent cranial window observation model was established by injecting autologous non-anticoagulation tail artery blood 0.3 ml twice in the occipital large pool and using a transparent flexible material made of silicon-based polydimethylsiloxane. Seven-day dynamic changes in cerebral cortical blood flow within the cranial window were monitored by laser speckle imaging. Results The imaging of 27 rats were clear; the blood flow velocity of the cortex decreased after SAH, which was statistically different from the control group and the saline group (P<0.01), and the blood flow on the 3rd, 5th, and 7th day after SAH. The percentage speeds were (83.20±4.16)%, (64.00±3.05)%, (75.70±3.79)%, and the 5 d was statistically different from the 3rd and 7 d (P<0.01); cortical blood perfusion after SAH The amount decreased, which was statistically different from the control group and the saline group (P<0.05). The percentage blood perfusion of the cortex on the 3rd, 5th, and 7th after SAH was (75.40±4.18)%, (31.80±5.34)%, (68.90±6.31)%, the 5th was statistically different from the 3rd and 7 d (P<0.01). Conclusion Through the use of a new flexible transparent material to establish a subarachnoid hemorrhage transparent cranial window imaging model, combined with laser speckle imaging technology can clearly detect the decline of cortical blood flow velocity and cortical blood perfusion in rats after subarachnoid hemorrhage 5 d is the peak of decline, and recovery begins on the 7th day, providing a new method for studying the pathophysiological changes in the acute and subacute phases after subarachnoid hemorrhage. Key words: Subarachnoid hemorrhage; Transparent cranial window imaging; Cerebral cortex blood flow; Laser speckle imaging technique; Rat

Abstract W P240: S1177-eNOS Phosphorylation Protects Against Stroke Injury in Akt1 Deficient Mice

Background: Phosphorylation of eNOS at serine 1177 (S1177) by Akt1 increases NO production and vascular reactivity. The goal of this study is to test the hypothesis that Akt1 deficiency increases susceptibility to stroke because of insufficient eNOS phosphorylation. Thus, constitutively phosphorylated eNOS will overcome Akt1 deficiency and protect against stroke. We generated knock-in mice (S1177D) carrying phosphomimetic mutation (serine to aspartate substitutions) in the eNOS gene. We bred S1177D mice with Akt1 knockout (Akt1KO) mice to test whether constitutively active eNOS could improve stroke outcome in Akt1KO mice. Methods: Adult male mice were anesthetized by 30% oxygen, 70% nitrous oxide, and 1.5% isoflurane. Body temperature was maintained at 36-37°C. The common carotid artery was catheterized to measure systemic blood pressure using a blood pressure transducer. For stroke studies we used the middle cerebral artery occlusion (MCAO) by filament with subsequent reperfusion with Laser Doppler cortical blood flow monitoring. Mice were examined for neurologic deficits by 5 point scale 24 hours after stroke. Infarct sizes were determined by the indirect method by 2,3,5-triphenyltetrazolium chloride staining. Results: Mean blood pressure was higher in Akt1KO (95±7 mmHg, Mean±SD, n=9) and WT mice (93±3 mmHg, n=8) than in S1177D/Akt1KO mice (80±11 mmHg, n=6, P&lt;0.05). One hour of MCAO with 23 hours of reperfusion produced increased cerebral infarct volume in Akt1KO mice (106±21 mm3, n=9) as compared with WT (70±33, n=9, p&lt; 0.05) mice. S1177D phosphomimetic mutation decreased cerebral infarct volume in Akt1KO mice (64±20 mm3, n=9, P&lt;0.05). This was associated with a functional impairment in the neurologic deficit, as quantities by neurologic scoring (2.7 point deficit for Akt1KO; 1.9 for WT and 1.3 for S1177D/Akt1KO mice). Conclusion: Stroke injury was more pronounced in Akt1KO mice than in WT mice. Introducing S1177D mutation in Akt1KO mice resulted in decreased infarct volume, neurological deficit and blood pressure. These results demonstrated that S1177D eNOS-derived NO is able to protect against stroke in the absence of Akt1.

Abstract 5037: Phosphorylation of eNOS Corrects Diabetic Vascular Dysfunction and Improves Outcome to Stroke

Background: While diabetes is associated with diminished vascular NO levels, the precise mechanisms of diabetic endothelial dysfunction are not known. We hypothesized that deficient eNOS S1179 phosphorylation plays a key role in diabetic vascular abnormalities, and that increasing S1179 phosphorylation may improve endothelial function. To test this hypothesis, we created eNOS knock-in mice that carry a S1179D mutation in the eNOS gene, resulting in the generation of a phosphomimetic form of eNOS with increased enzymatic activity and NO generation. We bred these animals to db/db mice to obtain S1179D-db/db mice to test whether modulation of the S1179 phosphorylation site could overcome diabetic vascular dysfunction, and whether this could affect stroke size in vivo. Experimental Procedures: Adult male mice were anesthetized by 30 % oxygen, 70 % nitrous oxide, and 1.5 % isoflurane. Body temperature was maintained at 36–37°C. Vessel reactivity studies were performed on isolated pressurized carotid arteries. For stroke studies we used the middle cerebral artery occlusion with subsequent reperfusion by filament with Laser Doppler cortical blood flow monitoring. Mice were examined for neurologic deficits 24 hours after stroke. Infarct sizes were determined by the indirect method by 2,3,5-triphenyltetrazolium chloride staining. Statistical analysis was performed with t-test. Results: Db/db mice showed normal levels of total eNOS, while S1179 phospho-eNOS was diminished. Db/db mice are hypertensive compared with wild-type (WT) mice (116±4 vs 93±3 mm Hg, mean± SEM). The eNOS S1179D mutation normalizes the blood pressure of db/db mice (92±5 mmHg). Carotid artery vasodilation to ACh was impaired in db/db mice (EC50 43.4±6.1 nM) compared with WT mice (16.3±2.9 nM) and S1179D-db/db mice (26.6±4.2 nM). Db/db mice show a larger stroke (100±7 mm3) than do WT (65±7 mm3) and S1179D-db/db mice (80±4 mm3, P&lt;0.05). This was associated with a functional improvement in the neurologic deficit. Conclusion: Our results establish eNOS phosphorylation as an important cause of vascular dysfunction in db/db mice, and suggest eNOS phosphorylation as a novel target for the treatment and prevention of diabetic vascular disease and stroke. This research has received full or partial funding support from the American Heart Association, National Center.

IRAP and AT1 receptor mediated effects of angiotensin IV

IRAP and AT₁ receptor mediated effects of angiotensin IV

The Selective Oestrogen Receptor Modulator, LY362321, is Not Neuroprotective in a Rat Model of Transient Focal Ischaemia

Selective oestrogen receptor modulators (SERMs) may offer improved alternatives to oestrogen as neuroprotectants in experimental stroke. The present study investigated the role of a novel SERM, LY362321, in a rat model of transient middle cerebral artery occlusion (MCAO). Female Sprague-Dawley rats were ovariectomised and began receiving daily s.c. injections of either 1 mg/kg (n = 13), 10 mg/kg (n = 14) of LY362321, or vehicle (n = 13). The left MCA was temporarily occluded (90 min), with cortical blood flow monitoring, at 12 days post ovariectomy. Sensorimotor function was assessed using a neurological score prior to the MCAO and daily for 3 days following the MCAO. Tissue was processed for infarct volume assessment using 2,3,5-triphenyltetra-zolium chloride staining. The results indicated that there were no significant differences amongst groups in cortical blood flow during the MCAO. Furthermore, there was no significant difference in infarct size amongst vehicle, 1, and 10 mg/kg treated animals: 22.9 +/- 5.0, 16.7 +/- 4.2, and 21.1 +/- 4.1, respectively, one-way anova [F(2,32) = 0.542, P = 0.587]. The MCAO induced a significant decline in neurological score in the vehicle group (from 14 to 7 at 24 h post-MCAO) but this was not significantly affected by LY362321 at either dose. In conclusion, pretreatment with a low or high dose of the novel SERM LY362321 did not significantly influence cerebral blood flow, infarct volume, or sensorimotor function in rats exposed to transient MCAO.

Monitoring of cortical blood flow: clinical relevance of experimental laser Doppler studies.

Continuous monitoring of cortical blood flow provides real time information of CBF-changes during neurosurgical operations and on the neurointensive care unit. Laser Doppler flowmetry is a continuous, noninvasive technique suitable for measurement of the cortical microcirculation. In a number of experimental studies we have analyzed the characteristics of this method for cortical blood flow monitoring. The high spatial resolution of laser Doppler flowmetry and the heterogeneity of the cortical microvascular network results in a scatter of flow values over a wide range depending on the site of measurement. Data collection from different spots and calculation of frequency histogram may serve as a measure of cortical blood flow. For clinical application instead of single fiber probes a multispot measurement approach will provide a reliable cortical blood flow monitoring. The use of continuous techniques will lead to a better understanding of cerebral hemodynamics under pathological conditions.

Continuous Regional Cerebral Cortical Blood Flow Monitoring in Head-injured Patients

Continuous Regional Cerebral Cortical Blood Flow Monitoring in Head-injured Patients

Continuous Regional Cerebral Cortical Blood Flow Monitoring in Head-injured Patients

Continuous regional cerebral cortical blood flow (rCoBF) was monitored with thermal diffusion flowmetry in 56 severely head-injured patients. Adequate, reliable data were accumulated from 37 patients (21 acute subdural hematomas, 10 cerebral contusions, 4 epidural hematomas, and 2 intracerebral hematomas). The thermal sensor was placed at the time of either craniotomy or burr hole placement. In 15 patients, monitoring was initiated within 8 hours of injury. One-third of the comatose patients monitored within 8 hours had rCoBF measurements of 18 ml per 100 g per minute or less, consistent with previous reports of significant ischemia in the early postinjury period. Initial rCoBF measurements were similar in the patients with Glasgow Coma Scale scores of 3 to 7 and in those with scores of 8 or greater. In patients with poor outcomes, rCoBF measurements did not change significantly from initial measurements; however, in those patients who had better outcomes, final rCoBF measurements were higher than initial rCoBF measurements. The patients who had better outcomes experienced normalization of rCoBF during the period of monitoring, and patients with poor outcomes had markedly reduced final rCoBF. These changes were statistically significant. When management was based strictly upon the intracranial pressure, examples of inappropriate treatment were found. For example, hyperemia and increased intracranial pressure treated with mannitol caused further rCoBF increase, and elevated intracranial pressure with low cerebral blood flow treated with hyperventilation increased the severity of ischemia. In 3 (5%) of 56 patients, wound infections developed. Continuous rCoBF monitoring in head-injured patients offers new therapeutic and prognostic insights into their management.

On the number of measurements necessary to assess regional cerebral blood flow by local laser Doppler recordings: a simulation study with data from 45 rabbits.

Laser Doppler fluxmetry may improve the monitoring of cortical blood flow in neurosurgical patients. So far, however, the variability of laser Doppler readings found in the cerebral cortex has prevented a consequent usage of the technique in clinical practice. The current report analyzes the regional variability of laser Doppler readings from experimental animals. Typical frequency histograms of observed flow values display non-Gaussian distributions. A simulation technique is used to assess the number of measuring sites required for valid estimates of regional cortical flow. From a total of 990 local flow measurements from 45 rabbits random samples of sizes between 5 and 100 were repeatedly drawn to estimate the variability of median flow thus determined. The study underlines that small sample sizes below n = 20 are associated with a large variability (95th percentile: +38%) which decreases in a biphasic manner. Sample sizes above n = 25 are necessary to obtain more reliable information on regional cerebral blood flow: the 95th percentiles remain between 24 and 28% up to n = 45, and are still at 15% with n = 99.

Cerebral blood flow (CBF) monitoring in intensive care by thermal diffusion.

Continuous monitoring of cortical blood flow (CoBF) in the intensive care unit is possible with thermal diffusion techniques. The normal brain flow limits have been established when electrical activity ceases and when infarction is likely to occur. With continuous monitoring of CoBF one can see immediate changes in flow and approaching these levels may be anticipated. The thermal diffusion system we have employed is based on the thermal conductivity of cortical tissue. As blood flow increases through the tissue, the conduction of energy away from the flow probe allows the sensor to detect changes in flow. This form of monitoring has been carried out in patients with subarachnoid hemorrhage, resection of cerebral mass lesions, severe craniotrauma, and intractable epilepsy. In subarachnoid hemorrhage, vasospasm can be identified and the efficacy of treatment determined with continuous monitoring of CoBF. During resection of mass lesions, increases in blood flow can be readily detected to document the recovery of brain tissue. Continuous monitoring of CoBF in epilepsy patients is now possible with the implantation of subdural electrodes. The increase in blood flow can be documented and it is apparent that a period of elevation of blood flow is quite short. Therefore, this may be helpful in determining when other forms of CBF determination, such as Single Photon Emission Computed Tomographic (SPECT) scanning should be performed. In patients with cranial trauma, different patterns of CoBF changes are apparent. Some patients may develop increased CoBF prior to elevation of intracranial pressure (ICP); other patients demonstrate a drop in CoBF as a response to increased ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring of cortical blood flow in human epileptic foci using laser Doppler flowmetry

We have used laser Doppler flowmetry (LDF) for real-time monitoring of regional cerebral blood flow (rCBF) during epileptic seizures recorded intracranially with subdural electrodes. The method was employed in six patients with medically intractable epilepsy undergoing preoperative evaluation for epilepsy surgery. rCBF was measured during 24-h video/EEG monitoring of seizures. Eleven seizures were recorded with simultaneous LDF and EEG by a combined subdural EEG electrode and laser Doppler probe. All seizures recorded on EEG were accompanied by distinct changes in rCBF. There was either an increase in blood flow up to 100% or a decrease by 30% from the basal levels. The ictal blood flow changes were similar comparing seizures within one patient, whereas striking differences were found between patients. The rCBF was also studied interictally. Different blood flow signal patterns were found correlating to the wakefulness of the patient. The LDF technique, combined with continuous EEG recording, appears to be a powerful tool for studying regional transient rCBF changes in association with focal epileptic seizure activity.

Limitation of temporary vascular occlusion during aneurysm surgery: Study by intraoperative monitoring of cortical blood flow

The limitations of temporary vascular occlusion during aneurysm surgery as evidenced by the postoperative ischemic symptoms in relation to cerebral blood flow were studied. Six of the 39 cases had postoperative ischemic neurological deficit. When residual cerebral blood flow was below 15 mL/min/100 g, transient symptoms were seen when temporary clipping was for 10–20 minutes. When more than 20 minutes of clipping was required, irreversible deficits were found. Correlations between residual cerebral blood flow, duration of temporary clipping, and postoperative ischemic symptoms were found. The monitoring of cortical cerebral blood flow is an effective means for determining the limits of temporary vascular occlusion.

Modified thermal diffusion flow probe for the continuous monitoring of cortical blood flow

A small thermal diffusion flow probe has been developed to monitor the dynamic changes in cerebral blood flow in small animals. Constantan wire was used as a heat source to make a miniature probe. The pair of thermocouples used to detect the heat gradient between two gold plates was elongated to avoid heat conduction between them, and this improvement allowed us to make quantitative measurements. After several basic experiments, local cerebral blood flow was measured simultaneously, using both the modified thermal probe and the hydrogen clearance method in four rabbits. A close relationship was obtained between the local cerebral blood flow values measured by hydrogen clearance (F, ml/100g/min) and the reciprocal of the thermocouple voltage (1/V;1/mV). The regression line was F = 29111(1/V - 1/226), (r = 0.92, P less than 0.001). We suggest that the modified thermal probe is a reliable and quantitative means of measuring flow. In addition, another probe modified for clinical use was evaluated. Continuous monitoring of local cerebral blood flow in postoperative patients was performed, and some illustrative cases are described.

Modified Thermal Diffusion Flow Probe for the Continuous Monitoring of Cortical Blood Flow

Abstract A small thermal diffusion flow probe has been developed to monitor the dynamic changes in cerebral blood flow in small animals. Constantan wire was used as a heat source to make a miniature probe. The pair of thermocouples used to detect the heat gradient between two gold plates was elongated to avoid heat conduction between them, and this improvement allowed us to make quantitative measurements. After several basic experiments, local cerebral blood flow was measured simultaneously, using both the modified thermal probe and the hydrogen clearance method in four rabbits. A close relationship was obtained between the local cerebral blood flow values measured by hydrogen clearance (F, ml/100g/min) and the reciprocal of the thermocouple voltage (1/V;1/mV). The regression line was F = 29111(1/V- 1/226), (r = 0.92, P&amp;lt;0.001). We suggest that the modified thermal probe is a reliable and quantitative means of measuring flow. In addition, another probe modified for clinical use was evaluated. Continuous monitoring of local cerebral blood flow in postoperative patients was performed, and some illustrative cases are described.

Monitoring of Cortical Blood Flow during Temporary Arterial Occlusion in Aneurysm Surgery by the Thermal Diffusion Method

Monitoring of Cortical Blood Flow during Temporary Arterial Occlusion in Aneurysm Surgery by the Thermal Diffusion Method

Continuous postoperative monitoring of cortical blood flow and intracranial pressure

A new technique to continuously monitor cortical blood flow and intracranial pressure in postoperative patients is described. A thermal diffusion flow probe with a pressure port is left in contact with the cortex at craniotomy. Post-operative intracranial pressure-cortical blood flow can be monitored and acute changes or trends are readily detected. The thermal flow probe has been previously compared with radioactive xenon ( 133Xe) clearance and hydrogen clearance methods of measuring cortical blood flow in animals. The technique gives a real-time quantitative indication of flow. Changes in cortical blood flow can be observed within a few seconds and the effects of treatment can be readily observed. Changes in flow due to vasospasm have been demonstrated in subarachnoid hemorrhage. It is anticipated that information learned from this method will aid in the management of patients with head trauma, tumors, and subarachnoid hemorrhage.

脳動脈瘤術中の脳圧迫, 低血圧, 一時動脈遮断時の皮質脳血流の測定

脳動脈瘤術中の脳圧迫, 低血圧, 一時動脈遮断時の皮質脳血流の測定

Monitoring of cortical blood flow during temporary arterial occlusion in aneurysm surgery by the thermal diffusion method

During aneurysm surgery, regional cortical blood flow (CoBF) was continuously monitored in 12 patients with a thermal diffusion flow probe in an attempt to assess the effects of temporary major arterial occlusion on blood flow and outcome. When the CoBF was above 30 ml/100 g/min, the safe period for temporary clipping applied distal to the perforators was 15 minutes. The occlusion time should be shortened when the CoBF is below 30 ml/100 g/min. Two patients suffered basal infarction, which was not detected by CoBF monitoring. Attention should be paid to the blood flow in the deep structures when a temporary clip is applied at a site proximal to the perforating branches. Direct measurement of CoBF may be of value in estimating the time that temporary occlusion of a major vessel can be tolerated.

Modulation of blood flow following excision of a high-flow cerebral arteriovenous malformation

The authors present a case in which a large high-flow arteriovenous malformation was totally excised. The success of the operation was in part attributed to the prevention of hyperperfusion breakthrough phenomena by the use of Selverstone clamps on the cervical carotid artery. Monitoring of cortical blood flow during surgery was found to be helpful.

Monitoring of cortical blood flow during excision of arteriovenous malformation by thermal diffusion method

The cortical blood flow adjacent to arteriovenous malformations was monitored in six patients before, during, and after excision of arteriovenous malformations using a thermal diffusion probe. In a large arteriovenous malformation, a progressive increase in cortical blood flow up to two times the preexcision value was noted with occlusion of the feeding arteries. Lowering arterial pressure to keep normal cortical blood flow during and after operation resulted in minimum brain edema and an excellent result. Direct measurement of cortical blood flow is of value in determining the precise level of hypotension to prevent brain edema and ischemia that may occur with excision of a large arteriovenous malformation.