Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping.

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.

Evaluation of Cerebral Hemodynamics with Color-Coded Duplex Sonography: Normative Values with Correction of Insonation Angles.

BACKGROUND: Transcranial color-coded sonography (TCCS) allows direct observation of arteries and the possibility of correcting the insonation angle for reliable evaluation of hemodynamics. We obtained TCCS reference values of the cerebral hemodynamics after correction of insonation angles. METHODS: We studied 195 healthy adults equally allocated into 3 age groups: 18-40, 41-60, and greater than or equal to 61 years. The middle (MCA), anterior (ACA), and posterior cerebral arteries (PCA) were evaluated through the temporal acoustic window using conventional pulsed transcranial Doppler and TCCS. Peak systolic, end diastolic, and mean blood flow velocities were registered, as well as pulsatility and resistance indices at 0° and with correction by alignment of insonation angle parallel to the blood flow vector. We derived normative values assuming both the parametric and nonparametric distributions. RESULTS: We excluded 33 participants due to inadequate acoustic window (10.3%), carotid disease (2.1%), and embryonic variants (4.6%), leaving out 162 for final analysis (50% female, median age 48 years). The 2.5th-97.5th percentiles of the corrected angle for MCA was 0°-60°, ACA 0°-44°, and PCA 30°-60°. After angle correction, 2.5th-97.5th percentiles for flow velocity of MCA, ACA, and PCA were 37.7-112.5 cm/s, 25.6-71.2 cm/s, and 29.2-80.8 cm/s, respectively. There were wide discrepancies between hemodynamics values obtained with insonation angles at 0° and after angle correction. No differences were found between ultrasound methods at exactly 0° or between hemispheres, however, there were differences according to age and sex. CONCLUSIONS: Specific normative tables should be used in TCCS when the corrected angle is greater than 0° since the hemodynamics values greatly differ after correction of the insonation angle. Further studies are necessary to determine critical cutoffs indicating disease.

Sex differences in cerebral autoregulation are unaffected by menstrual cycle phase in young, healthy women.

Sex is known to affect the prevalence of conditions such as stroke. However, effects of sex on cerebral blood flow regulation are still not well understood. Critical to this understanding is how fluctuations in hormones across the menstrual cycle affect cerebral autoregulation. We measured autoregulation in the early follicular, late follicular, and midluteal phases during spontaneous and induced blood pressure oscillations in 26 young, healthy individuals (13 women and 13 men, age: 26 ± 4 yr). Men participated three times, ~1-3 wk apart. Beat-by-beat blood pressure, heart rate, end-tidal CO2, and transcranial Doppler ultrasonography of the middle (MCA) and anterior (ACA) cerebral arteries were obtained. We did not find a difference in cerebral autoregulation across the menstrual cycle in women but found significantly improved autoregulation in the MCA and ACA of women compared with men. Women demonstrated significantly lower MCA gain (0.97 ± 0.13 vs. 1.17 ± 0.14%/mmHg, P = 0.001), higher MCA phase (46.1 ± 12.6 vs. 35.8 ± 7.9°, P = 0.019), and higher ACA phase (40.5 ± 10.8 vs 31.5 ± 8.5°, P = 0.040) during repeated squat-to-stand maneuvers. Women also had lower MCA gain (1.50 ± 0.11 vs. 1.72 ± 0.30%/mmHg, P = 0.029) during spontaneous fluctuations in pressure while standing and less of a decrease in MCA flow velocity (-18.7 ± 2.7 vs. -23.2 ± 6.0%, P = 0.014) during sit-to-stand maneuvers. Our results suggest that young women have improved cerebral autoregulation compared with young men regardless of menstrual cycle phase and that autoregulation is relatively robust to acute fluctuations in female sex hormones. NEW & NOTEWORTHY This is the first study to investigate thoroughly the effects of menstrual cycle phase and sex differences in cerebral autoregulation in young, healthy individuals. Cerebral autoregulation was unaffected by menstrual cycle phase during both repeated squat-to-stand and sit-to-stand maneuvers. However, women demonstrated significantly improved cerebral autoregulation in the middle and anterior cerebral arteries, suggesting women were able to maintain cerebral blood flow during changes in blood pressure more efficiently than men.

[Blood flow parameters in fetal anterior cerebral artery during the second and third trimester of gestation].

OBJECTIVE: To investigate hemodynamic parameters in 2 anatomical segments (S1 and S2) of anterior cerebral artery (ACA) in normal pregnancy during the second and third trimester of gestation.
 Methods: The peak systolic velocity (PSV), end diastolic velocity (EDV), time-average maximum velocity (TAMAXV), peak systolic velocity/end diastolic velocity (S/D), resistance index (RI), and pulsation index (PI) in S1 and S2 of fetal anterior cerebral artery (ACA) in 288 normal pregnant women were detected by power Doppler and pulsed Doppler. Multiple regression models were fitted to estimate the relation between Doppler variables and gestational age. The differences of hemodynamic parameters between ACAS1 and ACAS2 were compared.
 Results: The PSV, EDV, and TAMAXV of ACAS1 and ACAS2 were positively correlated with the weeks of pregnancy (P<0.001), all fitted with the cubic curve. The S/D, PI, and RI values of ACAS1 and ACAS2 were not correlated with gestational ages (P>0.05). The PSV, TAMAXV, S/D, PI, and RI of ACAS1 were significantly higher than those of ACAS2, while EDV in ACAS1 was lower than that in ACAS2 (P<0.05).
 Conclusion: The velocity parameters (PSV, EDV, TAMAXV) of the 2 anatomical segments (ACAS1 and ACAS2) are increased with the increase of gestational age in normal pregnant fetus during the second and third trimester of gestation, and the resistance parameters (S/D, PI, RI) are not significantly correlated with gestational age. Distribution of blood flow is different in the blood supply territory between ACAS1 and ACAS2.

An exploratory analysis of the influence of personality and emotional factors on cerebral blood flow responses during painful stimulation in Fibromyalgia.

This study explored the influence of certain personality traits (neuroticism, extraversion, psychoticism, alexithymia), emotional variables (depression, catastrophizing), and insomnia on cerebral blood flow (CBF) responses to painful stimulation in fibromyalgia, using functional transcranial Doppler sonography. CBF velocities were recorded bilaterally in the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) of 24 fibromyalgia patients during exposure to two painful pressure conditions: (1) fixed pressure (2.4 kg) and (2) an individually calibrated pressure to produce an equal-moderate subjective pain intensity in all participants (average, 3.5 kg). Psychological factors were assessed by means of questionnaires. Neuroticism, and the externally-oriented thinking dimension of alexithymia were positively, and extraversion was inversely, associated with specific components of ACA and MCA CBF responses. Regarding catastrophizing and depression, correlations were positive for the fixed pressure condition and negative for the equal subjective intensity condition. The findings suggest that alterations in central nervous pain processing in fibromyalgia vary according to psychological factors. While most of the observed associations reflect a linear increase in nociceptive processing with the magnitude of negative cognitive and emotional states, the inverse associations for catastrophizing and depression during more intense painful stimulation may be ascribed to anti-nociceptive effects due to activation of the defense reflex.

Vascular territorial segmentation and volumetric blood flow measurement using dynamic contrast enhanced magnetic resonance angiography of the brain.

This study proposes a method for territorial segmentation and volumetric flow rate (VFR) distribution measurement of cerebral territories based on time-resolved contrast enhanced magnetic-resonance-angiography (MRA). The method uses an iterative region-growing algorithm based on bolus-arrival-time with increased temporal resolution. Eight territories were segmented: (1) right and (2) left internal carotid arteries, including the middle cerebral artery (ICA+MCA), excluding the anterior cerebral arteries (ACA); (3) right and left ACA (R+L-ACA); (4) right and (5) left external carotid arteries (ECA); (6) right and (7) left posterior cerebral arteries (PCA); and (8) vertebrobasilar territory. VFR percentage, relative to the entire brain (rVFR), was measured based on territorial volume as a function of time. Mean rVFR values of fifteen healthy subjects were: ICA+MCA = 23 ± 2%, R + L-ACA = 17 ± 3%, ECA = 4 ± 2%, PCA = 12 ± 2%, and vertebrobasilar territory = 31 ± 4%. Excluding the ECA-rVFR, which is underestimated, these values are comparable to previously reported values. Six subjects were scanned twice, demonstrating comparable and even higher reproducibility than previously reported using phase-contrast, yet with faster scan time (∼1 min). This method was implemented in one patient with MCA occlusion and one with Moyamoya syndrome scanned before and after bypass surgery, demonstrating its clinical potential for quantitative assessment of the degree of occlusion and the effect of surgery.

Cognitive tasks and cerebral blood flow through anterior cerebral arteries: a study via functional transcranial Doppler ultrasound recordings.

BACKGROUND: Functional transcanial Doppler ultrasound (fTCD) is a convenient approach to examine cerebral blood flow velocity (CBFV) in major cerebral arteries. METHODS: In this study, the anterior cerebral artery (ACA) was insonated on both sides, that is, right ACA (R-ACA) and left ACA (L-ACA). The envelope signals (the maximum velocity) and the raw signals were analyzed during cognitive processes, i.e. word-generation tasks, geometric tasks and resting state periods separating each task. Data which were collected from 20 healthy participants were used to investigate the changes and the hemispheric functioning while performing cognitive tasks. Signal characteristics were analyzed in time domain, frequency domain and time-frequency domain. RESULTS: Significant results have been obtained through the use of both classic/modern methods (i.e. envelope/raw, time and frequency/information-theoretic and time-frequency domains). The frequency features extracted from the raw signals highlighted sex effects on cerebral blood flow which revealed distinct brain response during each process and during resting periods. In the time-frequency analysis, the distribution of wavelet energies on the envelope signals moved around the low frequencies during mental processes and did not experience any lateralization during cognitive tasks. CONCLUSIONS: Even if no lateralization effects were noticed during resting-state, verbal and geometric tasks, understanding CBFV in ACA during cognitive tasks could complement information extracted from cerebral blood flow in middle cerebral arteries during similar cognitive tasks (i.e. sex effects).

Microsurgical anatomy of the central lobe.

OBJECT: The central lobe consists of the pre- and postcentral gyri on the lateral surface and the paracentral lobule on the medial surface and corresponds to the sensorimotor cortex. The objective of the present study was to define the neural features, craniometric relationships, arterial supply, and venous drainage of the central lobe. METHODS: Cadaveric hemispheres dissected using microsurgical techniques provided the material for this study. RESULTS: The coronal suture is closer to the precentral gyrus and central sulcus at its lower rather than at its upper end, but they are closest at a point near where the superior temporal line crosses the coronal suture. The arterial supply of the lower two-thirds of the lateral surface of the central lobe was from the central, precentral, and anterior parietal branches that arose predominantly from the superior trunk of the middle cerebral artery. The medial surface and the superior third of the lateral surface were supplied by the posterior interior frontal, paracentral, and superior parietal branches of the pericallosal and callosomarginal arteries. The venous drainage of the superior two-thirds of the lateral surface and the central lobe on the medial surface was predominantly through the superior sagittal sinus, and the inferior third of the lateral surface was predominantly through the superficial sylvian veins to the sphenoparietal sinus or the vein of Labbé to the transverse sinus. CONCLUSIONS: The pre- and postcentral gyri and paracentral lobule have a morphological and functional anatomy that differentiates them from the remainder of their respective lobes and are considered by many as a single lobe. An understanding of the anatomical relationships of the central lobe can be useful in preoperative planning and in establishing reliable intraoperative landmarks.

Modifying flow in the ICA bifurcation: Pipeline deployment from the supraclinoid ICA extending into the M1 segment-clinical and anatomic results.

BACKGROUND AND PURPOSE: Utility of the Pipeline Embolization Device extending to the M1 and its clinical and flow consequences at the ICA bifurcation have not been characterized. We analyzed flow modification in cases where a single Pipeline Embolization Device was deployed from the M1 to the distal supraclinoid ICA, covering the A1, for aneurysm treatment. MATERIALS AND METHODS: A1 flow modifications and size regression in postprocedure and follow-up angiography were analyzed. Vessel diameters and ratios of the proximal A1 and M1 segments and the distal ICA were assessed. Relationships between Pipeline Embolization Device nominal diameter and the vessel diameters at landing zones were obtained. Clinical assessments after flow modification were documented. RESULTS: Six of 7 patients demonstrated no change of flow in the anterior cerebral artery/anterior communicating artery complex at immediate postembolization angiography. All patients who underwent follow-up angiography demonstrated size regression of the ipsilateral A1. Midterm follow-up angiography revealed complete reversal of flow in the ipsilateral A1 in 4 of 5 patients. One patient did not demonstrate flow modification. This patient had a dominant ipsilateral A1. Vessel ratios in this case demonstrated a unique configuration in favor of maintaining patency of the ipsilateral A1. There were no clinical or radiographic signs of ischemia. One patient experienced asymptomatic angiographic in-stent stenosis at the M1. CONCLUSIONS: We found that deployment of a Pipeline Embolization Device from the distal supraclinoid ICA to the M1 may result in reversal of flow in the anterior cerebral artery/anterior communicating artery complex and regression of the ipsilateral A1. Preoperative anatomic quantitation and sizing of the Pipeline Embolization Device may predict flow modification results.

Variability of resistive indices in the anterior cerebral artery during fontanel compression in preterm and term neonates measured by transcranial duplex sonography.

OBJECTIVE: To determine the normal range of resistive index (RI) variability in clinically/neurologically unremarkable preterm and term infants and to compare the hemodynamic response to transient elevation of intracranial pressure. STUDY DESIGN: We measured RIs at baseline and following brief fontanel compression, assessing for differences in mean baseline and compression values and percent change. RESULT: One hundred and twenty-nine subjects were included in the study. Mean baseline RI and normal range were 0.7 in preterm (0.54 to 0.86) and 0.66 in term infants (0.52 to 0.8; P=0.001). Mean RI during compression was 0.71 in preterm and 0.68 in term infants (P=0.015). Mean percent change between baseline and compression was 5.86% in preterm and 7.45% in term infants (P=0.092). CONCLUSION: No difference in the hemodynamic response to transient elevation of intracranial pressure between different gestational groups, suggesting no significant differences in autoregulatory response.

Blood flow velocity changes in anterior cerebral arteries during cognitive tasks performance.

OBJECTIVE: Transcranial Doppler sonography (TCD) enables monitoring of blood flow velocities (BFVs) in basal cerebral arteries during different cognitive tasks performance with great temporal resolution. So far, BFVs changes during mental activity were monitored primarily in middle cerebral arteries (MCAs) and little is known about these changes in anterior cerebral arteries (ACAs). AIM: To determine the effect of different cognitive tasks performance on BFV changes and hemispheric dominance in ACAs and to assess the most suitable activation test for monitoring of BFV changes in ACAs. METHODS: Fourteen right-handed, healthy subjects aged 20-26 were included in the study. BFVs in both ACAs were recorded simultaneously during performance of cognitive tasks designed to activate frontal lobes: phonemic verbal fluency test (pVFT), Stroop tests and Trail Making Tests (TMTs). RESULTS: A statistically significant BFV increase was recorded in both ACAs during performance of all cognitive tasks. Statistically significant right ACA dominance was found during performance of pVFT and TMTB. The most significant BFV increase was obtained during performance of TMTB. CONCLUSION: Our result addressed cognitive tests with great activation potential for monitoring of ACAs that might be used in distinguishing of healthy individuals and patients with neurovascular or neurodegenerative diseases.

Assessment of resting-state blood flow through anterior cerebral arteries using trans-cranial doppler recordings.

Trans-cranial Doppler (TCD) recordings are used to monitor cerebral blood flow in the main cerebral arteries. The resting state is usually characterized by the mean velocity or the maximum Doppler shift frequency (an envelope signal) by insonating the middle cerebral arteries. In this study, we characterized cerebral blood flow in the anterior cerebral arteries. We analyzed both envelope signals and raw signals obtained from bilateral insonation. We recruited 20 healthy patients and conducted the data acquisition for 15 min. Features were extracted from the time domain, the frequency domain and the time-frequency domain. The results indicate that a gender-based statistical difference exists in the frequency and time-frequency domains. However, no handedness effect was found. In the time domain, information-theoretic features indicated that mutual dependence is higher in raw signals than in envelope signals. Finally, we concluded that insonation of the anterior cerebral arteries serves as a complement to middle cerebral artery studies. Additionally, investigation of the raw signals provided us with additional information that is not otherwise available from envelope signals. Use of direct trans-cranial Doppler raw data is therefore validated as a valuable method for characterizing the resting state.

Changes in maternal posterior and anterior cerebral artery flow velocity during pregnancy and postpartum--a longitudinal study.

BACKGROUND: To evaluate the normal range of blood flow velocity in the maternal anterior (ACA) and posterior cerebral arteries (PCA) along the normal pregnancy and postpartum period. METHODS: Transcranial Doppler ultrasound was used to measure the systolic, diastolic, and mean blood velocities in the ACA and PCA during normal gestation. The resistance and pulsatility indices were calculated. Data were analyzed using multilevel modeling, incorporating random effects models, to construct mean and percentile curves. RESULTS: We performed 355 measurements on 59 patients, which showed that systolic and mean velocity in the ACA decreased, whereas diastolic velocity increased in the PCA during normal pregnancy. Resistance and pulsatility indices in both vessels increased to a maximum in the second trimester, decreased during the third trimester, and increased during the postpartum period. CONCLUSIONS: This study provides normative data for ACA and PCA velocity and indices during pregnancy and postpartum, demonstrating changes in velocity that suggest a shift of cerebral blood flow from the anterior to the posterior cerebral circulation.

Dependence of brain intravoxel incoherent motion perfusion parameters on the cardiac cycle.

Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM) MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion parameters ("pseudo-diffusion" coefficient D*, perfusion fraction f, and flow related parameter fD*) remain insufficiently characterized. In this article, we hypothesize that D* and fD*, which depend on blood speed, should vary during the cardiac cycle. We extended the IVIM model to include time dependence of D* = D*(t), and demonstrate in the healthy human brain that both parameters D* and fD* are significantly larger during systole than diastole, while the diffusion coefficient D and f do not vary significantly. The results non-invasively demonstrate the pulsatility of the brain's microvasculature.

Do TRPC-like currents and G protein-coupled receptors interact to facilitate myogenic tone development?

The objective of this study was to determine whether G(q/11)-coupled receptor activation can enhance the mechanosensitivity of a canonical transient receptor potential (TRPC)-like current and consequently the myogenic responsiveness of rat anterior cerebral arteries. Initial patch-clamp experiments revealed the presence of a basal cation current in isolated smooth muscle cells that displayed evidence of double rectification, which was blocked by trivalent cations (Gd(3+) and La(3+)). PCR analysis identified the expression of TRPC1, 3, 6 and 7 mRNA and, characteristic of TRPC-like current, the whole-cell conductance was insensitive to a Na(+)-dependent transport (amiloride), TRP vanilloid (ruthenium red), and chloride channel (DIDS, niflumic acid, and flufenamate) inhibitors. One notable exception was tamoxifen, which elicited a dual effect, blocking or activating the TRPC-like current at 1 and 10 µM, respectively. This TRPC-like current was augmented by constrictor agonists (uridine 5'-triphosphate and U46619) or hyposmotic challenge (303 to 223 mOsm/l), a mechanical stimulus. Although each stimulus was effective alone, smooth muscle cells pretreated with agonist did not augment the whole-cell response to hyposmotic challenge. Consistent with these electrophysiological recordings, functional experiments revealed that neither UTP nor U46619 enhanced the sensitivity of intact cerebral arteries to hyposmotic challenge or elevated intravascular pressure. In summary, this study found no evidence that G(q/11)-coupled receptor activation augments the mechanosensitivity of a TRPC-like current and consequently the myogenic responsiveness of anterior cerebral arteries.

Vascular geometry change because of endovascular stent placement for anterior communicating artery aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics have been shown to play an important role in the initiation and progress of intracranial aneurysms, and are considered well-related to vascular configuration. The purpose of this study was to quantify the vascular geometry change due to intracranial stent placement and to discuss its potential effects on hemodynamics. MATERIALS AND METHODS: Imaging data of patients with wide-neck AcomA aneurysms, treated with stent-assisted coiling between January 2005 and January 2010, were retrospectively analyzed. The angle between the afferent vessels (A1 segment) and the efferent vessels (ipsilateral or contralateral A2 segment) was calculated to determine the exact change in the angle after stent placement. RESULTS: In all 20 patients, the stent caused a distinct change in the geometry of the parent vessel. Stent-related vascular angle change ranged from 7.60 to 74.88°, with an average of 29.95°. In 10 cases, the angle changed by >30°. In the 12 patients with the distal segment of the stent placed in the ipsilateral A2 segment, the mean postoperative A1-A2 angle increased by 27.71 ± 13.17° (from 7.60° to 48.29°). In the other 8 patients with the distal segment of the stent placed in the contralateral A2 segment, the mean postoperative A1-AcomA-A2 angle increased by 33.29 ± 21.89°(from 15.49° to 74.88°). CONCLUSIONS: In addition to serving as a scaffold to contain coils, stent placement for AcomA aneurysms has a substantial effect on the vascular geometry, which may result in local hemodynamic changes.

Tamoxifen as an effective neuroprotectant in an endovascular canine model of stroke.

OBJECT: Tamoxifen has been shown to be a potent neuroprotectant against stroke in rodents. Because other neuroprotectant medications have failed in human trials, a study of tamoxifen in a large-animal model was necessary to further assess the drug's effectiveness. For this study, the authors developed an endovascular model of anterior circulation infarction in canines to mimic the human clinical condition. They assessed the following hypotheses: 1) that they will be able to consistently produce an internal carotid artery (ICA) terminus infarction and 2) that tamoxifen is an effective neuroprotectant against stroke in canines. METHODS: In 24 male beagles (weight 9-11 kg), bilateral femoral artery cutdowns were performed, and the vertebral artery and left ICA were each selectively catheterized. Under fluoroscopic guidance, a microcatheter was introduced via the vertebral artery, guiding the catheter into the basilar artery, posterior communicating artery, and ICA terminus. A 1-ml clot was injected in the terminus, occluding the middle cerebral artery (MCA) and anterior cerebral artery (ACA) origin. In the first 12 canines, the occlusions were confirmed by angiography. A Canine Stroke Score (CSS) was assigned (score range 0-18 [0 = intact on examination, 18 = comatose]). The animals were then killed and their brains stained with 2,3,5-triphenyltetrazolium chloride (TTC). The subsequent 12 canines underwent a blinded randomized study in which the authors compared the results of tamoxifen (5 mg/kg) infused intravenously 1 hour after clot injection with an equal volume of vehicle (dimethylsulfoxide). After 3 hours, the animals underwent MR imaging, were extubated, and clinical examinations were performed. The canines were killed at 8 hours after clot injection, and TTC staining was used. RESULTS: In the first group, infarct volume and CSSs were consistent with the extent of the occlusion of the angiographic vessels. An occlusion of the ACA, MCA, and posterior cerebral artery resulted in larger infarcts and higher stroke scores than occlusion of the ACA and MCA. In the second group, tamoxifen significantly reduced infarct size and improved clinical outcomes. In tamoxifen-treated animals, the mean infarct volume reduction was 40% (p < 0.05) and the mean CSS was significantly less than vehicle-treated animals (p < 0.001). There were significant correlations among MR imaging-determined volume, TTC-determined volume, and neurological clinical outcome (p < 0.05). CONCLUSIONS: Using this endovascular model of stroke, the authors were able to consistently produce an infarction in the canines that was similar in scope to a carotid terminus occlusion in humans. Also, angiography could predict subsequent clinical course and infarct size. Tamoxifen was effective at significantly improving the canine neurological deficits and reducing the size of the stroke. This study took the first step in demonstrating the effectiveness of a promising human neuroprotectant in a large animal.

Leptin augments cerebral hemodynamic reserve after three-vessel occlusion: distinct effects on cerebrovascular tone and proliferation in a nonlethal model of hypoperfused rat brain.

The adipocytokine leptin has distinct functions regulating vascular tone, inflammation, and collateral artery growth. Arteriogenesis is an inflammatory process and provides a mechanism to overcome the effects of vascular obstruction. We, therefore, tested the effects of leptin in hypoperfused rat brain (three-vessel occlusion). Systemic leptin administration for 1 week after occlusion surgery increased cerebral hemodynamic reserve similar to granulocyte-macrophage colony-stimulating factor (GM-CSF), as indicated by improved CO(2) reactivity (vehicle 0.53%±0.26% versus leptin 1.05%±0.6% per mm Hg arterial pCO(2), P<0.05). Infusion of microspheres under maximal vasodilation failed to show a positive effect of leptin on cerebral perfusion (vehicle 64.9%±4.5% versus leptin 66.3%±7.0%, occluded/nonoccluded hemisphere). Acute treatment with GM-CSF led to a significant increased CO(2) reactivity and cerebral perfusion (79.2%±8.1% versus 64.9%±4.5%, P<0.05). Vasoconstrictive response of isolated rat carotid artery rings, after phenylephrine was attenuated at 24 hours following preincubation with leptin, was unaffected by removal of endothelium but abrogated by coculture with N-(omega)-nitro-L-arginine methylester, pointing toward an inducible nitric oxide synthase-mediated mechanism. In chronic cerebral hypoperfusion, acute leptin treatment restored the hemodynamic reserve of the cerebral vasculature through its effects on vascular tone, while leaving vascular outward remodeling unaffected. Our results, for the first time, reveal a protective role of leptin on vascular function in hemodynamically compromised brain tissue.

Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler.

OBJECTIVE: To evaluate whether anterior cerebral artery (ACA) Doppler ultrasonography is superior to middle cerebral artery (MCA) Doppler in the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age (SGA) fetuses with normal umbilical artery (UA) Doppler. METHODS: MCA and ACA Doppler ultrasonography was performed in a cohort of SGA term fetuses with normal UA Doppler. Perinatal outcome and neonatal neurobehavioral performance were compared with a group of term appropriate-for-gestational age (AGA) infants. Neurobehavior was evaluated at 40 ( +/- 1) weeks of corrected age with the Neonatal Behavioral Assessment Scale. Differences between the study groups were adjusted for potential confounding variables by multiple linear or logistic regression analyis. RESULTS: A total of 199 newborns (98 SGA and 101 AGA) were included. Among the SGA fetuses, 28.6 and 17% had MCA and ACA redistribution, respectively. Cases with either type of redistribution had an increased risk for adverse outcome, with no differences in predictive performance between the two parameters. SGA fetuses with MCA redistribution compared with controls had an increased risk for abnormal neurobehavioral performance in motor (36 vs. 20%; adjusted P = 0.02) and state organization (25 vs. 17.5%; adjusted P = 0.03) areas. SGA fetuses with ACA redistribution had only an increased risk for abnormal neurobehavioral performance area in state organization compared with controls (30 vs. 17.5%; adjusted P = 0.021). CONCLUSION: In term SGA newborns with no signs of brain-sparing, ACA Doppler investigation does not provide any benefit over MCA in terms of the prediction of adverse perinatal outcome.

Anterior cerebral artery amputation and salvage repair of internal carotid artery tear: technical case report.

OBJECTIVE: We describe a novel technique used to repair an unanticipated tear of the internal carotid artery (ICA) requiring anterior cerebral artery (ACA) amputation to allow primary repair of the arteriotomy. CLINICAL PRESENTATION: A 59-year-old woman underwent an orbitozygomatic craniotomy to treat a large, suprasellar, thyroid-stimulating hormone-secreting adenoma. During resection, an incidental ICA tear occurred opposite the exit of the middle cerebral artery. TECHNIQUE: After an ICA tear on the wall opposite the middle cerebral artery occurred, clips were placed on the ICA, middle cerebral artery, and ACA. Primary closure was not feasible without critically stenosing the ICA. The ipsilateral ACA was clipped and amputated just distal to its origin. The relaxation afforded by amputating the ACA allowed primary suture repair of the arteriotomy. A clip was placed on the proximal ACA stump. The distal ACA stump revealed good backflow and was also clipped. CONCLUSION: When an arteriotomy of a large intracranial artery cannot be repaired primarily, creative alternatives must be considered. Amputation of a branch artery with sufficient collateral flow is a method to afford adequate relaxation for primary repair of an arteriotomy. This novel method should be considered in the armamentarium of neurosurgeons to minimize the impact of potentially disastrous vascular complications.