Cerebral blood flow regulation under activation of the primary somatosensory cortex during electrical stimulation of the forearm.

Coupling of neuronal activity to cerebral blood flow (CBF) is widely accepted, but the exact mechanism is still under investigation. We assessed the responses of CBF coupled with electrical activity over the primary somatosensory cortex (S-I) during electrical stimulation of the contralateral forearm in cats. CBF in S-I was monitored using laser-Doppler flowmetry (LDF), and electrical activity was recorded with a tungsten microelectrode. The effects of varying stimulus intensity and frequency were examined to assess the optimal stimulation parameters. CBF increased within 10 sec after onset of stimulation, sustained the plateau level, and returned to the pre-stimulus level after cessation of stimulation. The maximum response was obtained at 4 Hz under a constant intensity. Optimal stimulus intensity at 4 Hz ranged from 8 to 10 V. At intensity higher than 10 V, CBF increases reached a near-plateau level, while mean arterial blood pressure (MABP) decreased slightly. Electrical activity was recorded at the same restricted area where CBF increased. Low frequency components of the power spectrum of electrical activity increased as the CBF increase became greater. A tight coupling of CBF increases to neuronal activation is suggested, and CBF regulation may be affected by stimulation parameters.

Neural activation of the brain with hemodynamic insufficiency.

Little is known about how ischemia affects hemodynamic responses to neural activation in the brain. We compare the effects of a motor activation task and a cerebral vasodilating agent, acetazolamide (ACZ), on regional cerebral blood flow (rCBF) in primary sensorimotor cortex (PSM) in six patients with major cerebral artery steno-occlusive lesions without paresis of the upper extremities. Quantitative rCBF was measured in all patients using H2(15)O autoradiographic method and positron emission tomography. The CBF was determined at rest, during a bimanual motor activation task, and 10 minutes after ACZ administration. With bimanual motor activation, rCBF increased significantly in both PSM compared with at rest (P < 0.01 on lesion side, and P < 0.02 on contralateral side). However, rCBF did not increase after ACZ injection in the PSM on the lesion side, whereas rCBF increased significantly in the contralateral PSM after ACZ injection compared with the level at rest. This result suggests that despite a decreased hemodynamic reserve, there is a nearly normal flow response to neural activation, indicating that the mechanism of vasodilation responsible for perfusion change is different for acetazolamide and neural activation. The relations among neural activation, hemodynamic status, and cerebral metabolism in the ischemic stroke patients are discussed.

[A case of hemangiopericytoma with multiple extracranial metastasis: a case report].

A case of a patient with hemangiopericytoma with multiple extracranial metastasis, who has survived for more than twenty years is reported. A fifty-five-year-old male presented brain tumor twenty years ago. He underwent total removal of the tumors, but recurrences occurred each time. Liver metastasis was found seven years ago. After that multiple metastases extended to the lung, vertebra and pancreas and operations and irradiations were performed. At present, there is no progression of the tumors and he enjoyed a high quality of life. We concluded that, to ensure long time survival, a patient with hemangiopericytoma must be monitored carefully for local recurrence and systemic metastases.

Human dural thickness measured by ultrasonographic method: reflection of intracranial pressure.

We measured changes in dural thickness to estimate intracranial pressure. The dural thickness on magnetic resonance imaging with contrast enhancement was compared in a hydrocephalic patient before and after shunt operation. Dural thickness also was measured directly using a micrometer at craniotomy for aneurysmal clipping in 11 patients. A small ultrasound probe (5 MHz) was held against the temporal scalp of 10 volunteers to extract convoluted interference echoes from the dura mater using a computer--based system for fast Fourier transform-Cepstrum analysis and maximum entropy analysis. The degree of intracranial pressure in the supine position was varied in the volunteers with transient neck compression. The enhanced dural thickness of the patient with hydrocephalus, barely visualized before shunt operation, increased after surgery. Dural thickness measurements obtained ultrasonographically in the supine position were similar to direct measurements of thickness. Changes in dural thickness on ultrasonography reflect changes in intracranial pressure.

Comparison of vasodilatory effect of carbon dioxide inhalation and intravenous acetazolamide on brain vasculature using positron emission tomography.

Carbon dioxide (CO2) and acetazolamide are increasingly being used as vasodilators to detect cerebrovascular reserve capacity in patients of chronic cerebrovascular disease. The functional cerebrovascular reserve or ability of cerebral vessels to lower their resistance in response to decrease in cerebral perfusion pressure is expressed as change in cerebral blood flow from baseline under a vasodilatory stimuli. Theoretically a vasodilator causing maximum vasodilation, and thereby expressing complete reserve capacity would be more suitable for such a purpose. We quantitatively compared the vasodilating effect of 5% CO2 inhalation and 1 g of intravenous acetazolamide by positron emission tomography. Cerebrovascular reserve was quantified in six patients with chronic cerebrovascular disease in the same sitting, using oxygen-15 labeled water (H2(15)O) positron emission tomography at rest, during 5% CO2 inhalation and after 1 g intravenous acetazolamide. A significant linear correlation in both nonlesion hemisphere (r = 0.701, p < 0.001) and in lesion hemisphere (r = 0.626, p < 0.005) was found between CO2 and acetazolamide for cerebrovascular reserve capacity. This correlation improved by considering cerebrovascular reserve per unit change in arterial carbon dioxide (r = 0.744, p < 0.001 in nonlesion hemisphere and r = 0.721, p < 0.001 in lesion hemisphere). The quantitative value of global reserve capacity was different by CO2 stimuli (5.2%) and acetazolamide (49.7%). Though a similar vasodilatory response is elicited by both vasodilators, acetazolamide seems to be more potent and therefore should be preferred to detect patients with exhausted cerebrovascular reserve capacity.

Magnetic resonance imaging quantitation of superior sagittal sinus flow: correlation to cerebral blood flow measured by xenon-enhanced computed tomography.

We compared measurements of venous blood flow velocity in the superior sagittal sinus (SSS) obtained by magnetic resonance imaging (MRI) and quantitative measurements of cerebral blood flow (CBF) obtained by xenon-enhanced CT, in neurosurgical patients and normal volunteers, to assess the clinical usefulness of MRI for determination of CBF. Flow measurements were obtained in 15 neurosurgical patients and 3 normal volunteers. SSS velocimetry was performed using the direct bolus imaging technique with a 1.5-tesla MRI system near the point of lambda on a sagittal MR image. Quantitative CBF was measured by xenon-enhanced CT and correlated with SSS flow velocity. We also examined the effect of surgical evacuation of a hematoma or cranioplasty in 3 patients, mannitol in 5 patients and acetazolamide in 4 patients by performing SSS velocimetry. The peak SSS flow velocity during the entire cardiac cycle was 27.2 +/- 6.3 cm sec-1 (mean +/- SD) in normal volunteers and 23.5 +/- 8.9 cm sec-1 in patients. The SSS flow velocity increased after surgery. Mean SSS peak flow velocity increased by 24% and 48% at 10 min after administration of mannitol and acetazolamide, respectively. SSS peak flow velocity showed significant linear correlations with both cerebral cortical (r = 0.74) and hemispheric flows (r = 0.73). Our results suggest that SSS flow velocity reflects CBF and that MRI assessment of SSS flow provides a simple method for assessing and monitoring global changes in cerebral hemodynamics.

Effect of glycerol on blood flow distribution in tumoral and peritumoral brain tissue.

To evaluate the effect of glycerol, thirty-two patients with brain tumor were directed to the study, including 17 gliomas and 15 meningiomas. Blood flow before and after the administration of glycerol were measured with Xe CT. Glioma was significantly hypo-perfused. The peritumoral edema of glioma and meningioma were also hypo-perfused. On the other hand, Meningioma was significantly hyper-perfused. After the administration of glycerol, blood flows were increased except for glioma. We suggested that, vascular responses to glycerol was different in the two tumor types. The steal phenomena of blood flow might occur in glioma.

Assessment of vasoreactivity in brain edema by acetazolamide activation SPECT and PET.

Our study was performed to find out cerebrovascular reactivity post acetazolamide administration in patients with peritumoral edema. Adult patients (n = 9) underwent CBF measurement by 99mTc-HMPAO SPECT pre and post 1 gram i.v. acetazolamide. In all patients, this procedure was repeated once again within 10 days of performing tumor removal. Five of these patients also underwent CBF measurement pre and post 1 gram i.v. acetazolamide post surgery only using oxygen-15 labeled H2O PET. Asymmetry index (AI) was calculated as ratio of ROI counts in the peritumoral edematous area and symmetrical ROI on the contralateral normal hemisphere. The AI increased after acetazolamide in edematous gray matter post operatively though the resting AI remained almost same post operatively. AI in edematous white matter showed non-significant increase post operatively both at rest and after acetazolamide. Good linear correlation of AI between PET and SPECT was observed both in gray and white matter. The improvement of vascular reactivity in edematous gray matter after tumor removal suggests that mass effect not only reduces CBF but also suppresses vascular reactivity. White matter vascular reactivity in early post operative period is little improved, possibly due to factors other than mass effect i.e. excess water accumulation in white matter perivascular space.

Induction of matrix metalloproteinases following brain injury in rats.

Matrix metalloproteinases (MMPs) are important in various pathophysiological processes related with the tissue remodeling. We planned the experiments to determine whether MMPs participate in disruption and repair of the tissue following brain injury. We have studied induction of MMP-9, a 92 kilodalton (kDa) gelatinase, in traumatic brain tissue, which may be produced by brain residual cells. We speculate that MMP-9 plays a role in post-traumatic brain edema formation.

Responses of cerebral blood flow regulation to activation of the primary somatosensory cortex during electrical stimulation of the forearm.

We assessed the cerebral blood flow (CBF) response to electrical stimulation of the contralateral forearm over the primary somatosensory cortex (S-I) in anesthetized cats. CBF was monitored continuously using laser-Doppler flowmetry (LDF). In the first set of experiments, the effects of varying stimulus frequency and intensity were examined. During stimulation, CBF in S-I was increased significantly. At high stimulus intensity, response reached a near-plateau level. In the second set of experiments, the CBF response after introduction of an intracerebral mass was investigated using a mechanical microballoon model to simulate an intracerebral hematoma. A microballoon was inserted into the ventral posterolateral nucleus of the thalamus (VPL). Following gradual balloon inflation, there was a rapid reduction in CBF response. We conclude that CBF regulation to neuronal activation is affected by stimulation parameters, and is impaired by an intracerebral mass obstructing the afferent sensory pathway.

Intercellular adhesion molecule-1 expression on glia following brain injury: participation of interleukin-1 beta.

Interleukin-1 (IL-1), one of the most important inflammatory cytokines, promotes glia to express intercellular adhesion molecule-1 (ICAM-1) in vitro. IL-1 is known to be produced in situ immediately after brain insults and recently we have found that glia, including astrocytes, express ICAM-1 in vivo following cortical stab wounds. To evaluate the participation of IL-1 beta in posttraumatic ICAM-1 expression on glia in vivo, we performed the following experiments. A cortical stab wound was made in the brain of a mouse. ICAM-1-immunopositive glia began to emerge around the wound from 6 h postlesioning. The number of cells reached a maximum at 48 h and persisted until 7 days postlesioning. Next, a neutralizing monoclonal antibody against IL-1 beta was infused into the wound immediately following the injury. This treatment resulted in a significant reduction of ICAM-1-positive glia at 24 and 48 h postlesioning. We conclude, therefore, that IL-1 beta affects ICAM-1 expression on glia in vivo after experimental brain injury and presumably plays an important role in brain wound repair.

Intraoperative laser flowmetry reflects levels of cerebral blood flow during neurosurgical procedures.

Changes in cerebral blood flow (CBF) during craniotomies (mean 62.2 years, n = 31) were studied using a laser flowmeter (LFM) to evaluate the utility in CBF monitoring. A small flat probe was applied to the brain surface near the surgical field. The output voltage from LFM was recorded as CBF changes. The percent change in CBF was calculated using the formula [intrasurgical-CBF-control-CBF]/control-CBF x 100. Post-operative neurologic status was evaluated. Control-CBF values were similar among the groups representing different pathologies. The mean CBF decrease ranged from -7.3% following phenytoin injection (n = 9) to -32.7% during induced intrathoracic pressure (n = 10). The mean CBF increase was 41.4% following vascular anastomosis. A decrease > 50% for more than 15 min was associated with a severe permanent neurologic deficit. The CBF monitoring using an LFM during craniotomy may be useful in detecting critical CBF levels for reducing post-operative neurological deficits.

Dynamics of cerebral blood flow and metabolism in patients with cranioplasty as evaluated by 133Xe CT and 31P magnetic resonance spectroscopy.

OBJECTIVE: Prolonged improvement in neurological and mental disorders has been seen after only cranioplasty in patients initially treated with external decompression for high intracranial pressure. The objective was to evaluate, using 133Xe CT and 31P magnetic resonance spectroscopy (MRS), how restoring the bone itself can influence cerebral blood flow and cerebral energy metabolism after high intracranial pressure is attenuated. METHODS: Seven patients (45-65 years old) who had undergone external decompression to prevent uncontrollable intracranial hypertension after acute subarachnoid haemorrhage were evaluated. Cerebral blood flow and metabolic changes were evaluated before and after cranioplasty. RESULTS: The ratio of phosphocreatine to inorganic phosphate (PCr/Pi), which is a sensitive index of cerebral energy depletion, was calculated and beta-ATP was measured. The cerebral blood flow value in the thalamus was normalised, from 44 (SD 9) to 56 (SD 8) ml/100 g/min (P < 0.01) and the value in the hemisphere increased from 26 (SD 3) to 29 (SD 4) ml/100 g/min on the side with the bone defect. The PCr/Pi ratio improved greatly from 2.53 (SD 0.45) to 3.01 (SD 0.24) (P < 0.01). On the normal side, the values of cerebral blood flow and PCr/Pi increased significantly (P < 0.01) after cranioplasty, possibly due to transneural suppression. The pH of brain tissue was unchanged bilaterally after cranioplasty. CONCLUSION: Cranioplasty should be carried out as soon as oedema has disappeared, because a bone defect itself may decrease cerebral blood flow and disturb energy metabolism.

Posterior communicating artery section during surgery for basilar tip aneurysm.

Although dividing the posterior communicating artery (PComA) during surgery has been criticized for increasing the risk of ischaemia, this procedure increase working space improving visibility and the ability to manipulate during treatment of basilar tip aneurysms via the pterional approach. We divided a hypoplastic PComA in 4 of our cases of basilar tip aneurysm. This was necessary because either (1) the length of the PComA and intracranial internal carotid artery (ICA) limited medial retraction of the ICA and access to the basilar bifurcation region, or (2) the PComA and its perforators ran just in front of the aneurysm, interfering with its exposure. We were able to clip the aneurysm neck in all four patients, three of whom had complications including temporary impairment of consciousness, ocular movement disorders and altered sensation in the extremities. Patients with complications showed transient hypersomnolence immediately after surgery; computed tomography showed small thalamic infarctions. However, in two of three patients the ischaemic events occurred contralateral to the side of PComA section. All patients regained consciousness within a week and were discharged with mild ocular movement palsies. In our cases except one with ischaemic complications, thalamic infarction probably resulted from thalamo-perforating artery injury when the aneurysm neck was clipped, rather than tuberothalamic artery injury due to section of the PComA. Taking previous reports and our results into consideration, we believe that division of a hypoplastic PComA is a safe procedure in particular cases when the grade of subarachnoid haemorrhage is not poor and there are no cerebrovascular risk factors, although we realize it is desirable to preserve normal blood flow.

Changes in dural thickness reflect changes in intracranial pressure in dogs.

The thickness of the dura mater was obtained from ultrasound probes on the skull and fast Fourier transform-Cepstrum through a probability process at various intracranial pressures (ICP), measured with pressure transducers, in 12 anesthetized dogs. There was a constant relationship between changes in thickness (micron) and changes in ICP (mmHg) from 5 to 80 mmHg. The estimated thickness at 0 mmHg of pressure and values obtained from measurements of dural samples were very similar. Our method provides estimations of ICP, and holds promise for measuring thicknesses below 1000 microns in biological systems in general.

Changes in the cerebrocortical capillary network following venous sinus occlusion in cats.

BACKGROUND: Although the important protective effect of venous collateral pathways in sinus occlusion on parenchymal injury has been demonstrated in previous works, the vascular response in the capillary microcirculation itself after cerebral venous occlusion has not been fully elucidated. We examined the morphology of the capillary network after venous occlusion by relating stereologic morphometric parameters to changes in local cerebral blood flow and the development of brain edema. METHODS: Experimental venous sinus occlusion was induced by injection of 0.5 mL of cyanoacrylate into the superior sagittal sinus and by immediate ligation of both external jugular veins in chloralose-urethane anesthetized cats (n = 24). Capillaries in the adjacent cortex (marginal and suprasylvian cortex) and remote cortex (piriform cortex) were injected with Evans blue dye 2 minutes before sacrifice at 15-minute and 120-minute postsinus occlusion. The stereologic morphometric parameters including volume density, minimum intercapillary distance, capillary diameter, and number of perfused capillaries were computed on a fluorescence microscopic photograph using an image analysis system. Cerebral blood flow (CBF) was measured by hydrogen clearance method, and brain tissue water content was measured using the dry-wet method. RESULTS: In the cortex adjacent to the superior sagittal sinus, the volume density and the number of perfused capillaries were increased significantly (p < 0.02, and p < 0.05, respectively) and the minimum intercapillary distance was decreased significantly (p < 0.02) at 15 minutes after venous occlusion (n = 10). Cerebral blood flow (CBF) was also decreased to 53% of that in the control group (p < 0.01). Although the morphologic parameters returned to the control level by 120 minutes after venous occlusion, the CBF remained decreased after venous occlusion. No change was observed in the water content of the adjacent gray matter at 15 minutes after venous occlusion; however, it was increased (p < 0.05) at 120 minutes. CONCLUSION: These results indicate that the recruitment of reserve capillaries occurs during the early phase of venous occlusion. While CBF decreased to half of the control after venous occlusion, capillary perfusion remained above or near the control level until 120 minutes postocclusion, suggesting that venous recruitment would be potentially beneficial in clinical patients in the early stage of venous occlusion.

Effect of intracarotid administration of 6-aminonicotinamide on cerebral blood flow in cats.

BACKGROUND AND PURPOSE: We evaluated the effects of an adenosine triphosphate blocker, 6-aminonicotinamide (6-ANA), on the cerebral blood flow (CBF), cerebral metabolism, and electroencephalogram of cats. METHODS: Catheters were inserted into the common carotid artery of 16 adult cats anesthetized with ketamine via the lingual artery. We measured CBF in the infused area by the inhaled hydrogen gas clearance method and analyzed the electroencephalogram frequency. Cerebral metabolism was estimated by oxygen extraction (vol/%) and glucose utilization (millimoles) using data arterial (aorta) and sagittal sinus blood samplings. A solution of 6-ANA (6.0 mg/mL) (n = 8) or saline (n = 8) was infused via catheter at 2.0 mL/min for 3 minutes followed by a 60-minute observation of CBF, cerebral metabolism, vascular resistance, and the electroencephalogram components, alpha-2 ratio [= alpha-2/(alpha-1+alpha-2)]. The effect of 6-ANA on capillaries was evaluated by extravasation of Evans blue dye and electron microscopic findings. RESULTS: Moderate reductions in CBF, cerebral metabolism, and the alpha-2 ratio were observed during the infusion of 6-ANA versus saline infusion (P < .05 by paired t test and ANOVA). Vascular resistance was significantly increased (P < .05). No abnormalities were observed in the capillaries of the infused hemisphere. CONCLUSIONS: Results indicated that 6-ANA produced a downregulation of cerebral blood flow in cats.

Computerized tomography in the assessment of brain shifts in acute subdural hematoma.

Computed tomography (CT) was used to characterize brain shifts in 30 adult patients (mean age 51.9 years) with fatal supratentorial acute subdural hematomes (ASH) who were admitted within 3 hours of the head trauma. The Glasgow Coma Scale (GCS) score, hematoma width, and midline shift were tabulated. The width of the cistern surrounding the brainstem (CSBS) and the distance from the floor of the fourth ventricle to the posterior clinoid process (IVv-PC) were measured. Opening (+) or disappearance (-) of the suprasellar cistern (SC) was determined using axial CT. The data were compared with those in agematched controls (n = 26) using the Wilcoxon and Kruskal-Wallis tests. The hematomas in the SC(-) group (n = 22, mean GCS score: 3.8 +/- 1.0) were wider (p = 0.02) than those in the SC(+) group (n = 8, mean GCS score: 4.7 +/- 1.5). The CSBS in the SC(+) group was significantly smaller than that in the controls (p < 0.01). In the SC(-) group the CSBS was smaller and the IVv-PC was significantly larger than those in the controls (IVv-PC; p < 0.01) and the SC(+) group (IVv-PC; p < 0.05). In the evolution of brainstem shifts in ASH, when the SC is open the predominant vector is in the direction of the skull base, while when the SC is not observed, an axial vector shifts the brainstem.

Dynamics of cerebral metabolism in patients with chronic subdural hematoma evaluated with phosphorous 31 MR spectroscopy before and after surgery.

PURPOSE: To determine whether the depression of cerebral bioenergetic metabolism caused by chronic subdural hematomas can account for neurologic dysfunction and whether the degree of metabolic depression may be useful for clinical assessment and therapy. METHODS: Sixteen patients who had chronic subdural hematomas with hemiparesis and/or mental disturbances underwent phosphorous 31 MR spectroscopy before and 10 to 14 days after surgery. Phosphorous 31 MR spectroscopy was also performed on 5 patients who had chronic subdural hematomas with only slight headaches who were treated by conservative therapy and on 10 healthy volunteers. RESULTS: The peroperative phosphocreatine-to-inorganic phosphate ratio (2.10 +/- 0.36) improved to normal values (2.69 +/- 0.44) after evacuation of hematomas. This improvement was accompanied by complete disappearance of hemiparesis and/or mental disturbance. Brain tissue pH also improved from 7.07 +/- 0.11 to 7.205 +/- 0.13 after surgery. On the other hand, patients who had chronic subdural hematomas with only slight headaches had the same phosphocreatine-to-inorganic phosphate ratio and brain intracellular pH as healthy volunteers. CONCLUSION: The phosphocreatine-to-inorganic phosphate ratio may be useful for determining when to operate on patients with chronic subdural hematomas and to assess the efficacy of treatment.

An assessment of progression of brain edema with amino acid levels in cerebrospinal fluid and changes in electroencephalogram in an adult cat model of cold brain injury.

We investigated the relationship between the changes of the electroencephalogram (EEG) and concentration of amino acids (AAs) in cerebrospinal fluid (CSF) using a model of cold brain injury. A cold injury was made over the motor area of anesthetized adult cats (n = 45). The AAs in CSF from cisterna magna and in the blood were assayed by liquid chromatography. Frequency components and spike discharges/100 s in EEG were evaluated. Data were obtained before production of the lesion and every hour for 8 hours after the lesion was made. The AA-levels and EEG after the lesion was made were compared with those obtained in the controls and the sham operation group: S-group (n = 10) which were not significantly different. Glutamate and aspartate were not detected but methionine and serine were detected in the control CSF and S-group. These AAs increased during the first 4 hours (p < 0.05) and decreased thereafter. Significant increases in spike discharge and disappearance of fast wave (p < 0.02), and increase in AAs were concurrently detected. The AAs originated from necrosis in the lesion. During the next 4 hours, increase of phenylalanine, tyrosine, and valine continued (p < 0.05). Slow wave components (p < 0.02) and precursor AAs of neurotransmitters in CSF increased in association with expansion of edema fluid. In conclusion, our findings showed that changes in the concentration of AAs in CSF are useful indices of progression of edema associated with brain contusion.