Effect of transient forebrain ischemia on flavoprotein autofluorescence and the somatosensory evoked potential in the rat.

In order to evaluate the effect of cerebral ischemia on the flavoprotein fluorescence (FPF), we compared the changes in the FPF and somatosensory evoked potential (SEP) during transient cerebral ischemia in the rat. We measured the FPF and SEP simultaneously via a cranial window made over the right sensorimotor cortex during the left median nerve stimulation in F344 rats. We compared change in FPF and SEP during cerebral ischemia for 60 min. The rCBF were rapidly recovered after reperfusion. However, the recovery rates of the FPF were significantly faster than those of the SEP after reperfusion. These findings indicate that activity-dependent changes of the FPF do not necessarily correlate with the electrical activity after transient cerebral ischemia.

Theoretical and experimental investigation of the influence of frontal sinus on the sensitivity of the NIRS signal in the adult head.

The sensitivity of the near-infrared spectroscopy signal to the brain activation depends on the thickness and structure of the superficial tissues. The influence of the frontal sinus, which is void region in the skull, on the sensitivity to the brain activation is investigated by the time-resolved experiments and the theoretical modelling of the light propagation in the head. In the time-resolved experiments, the mean-time of flight for the forehead scarcely depends upon the existence of the frontal sinus when probe spacing was shorter than 30 mm. The partial optical path length in the brain, which indicates the sensitivity of the near-infrared spectroscopy signal to the brain activation, in a simplified head model is predicted by Monte Carlo simulation. The influence of the frontal sinus on the sensitivity of the signal depends on the thickness of the skull and the depth of the frontal sinus.

Comparison of somatosensory evoked potentials and cerebral blood oxygenation changes in the sensorimotor cortex during activation in the rat.

The relationship between changes in cerebral blood oxygenation and neuronal activity remains to be fully established. We compared somatosensory evoked potentials (SEP) and evoked cerebral blood oxygenation (CBO) changes in the sensorimotor cortex of the rat. In rats anesthetized with urethane and alpha-chloralose, we measured SEP and CBO using visible light spectroscopy (VLS) during neuronal activity. Increase of stimulus frequency caused a decrease of SEP amplitude, but an increase in concentration changes of deoxy-Hb and oxygen saturation. The difference in frequency responses between SEP and CBO might be caused by activation of inhibitory neurons, which could suppress excitatory neurons at high stimulus frequencies; activation of inhibitory neurons could reduce SEP amplitude, and increase oxygen saturation due to an increase of evoked cerebral blood flow.

Changes in cerebral blood oxygenation and hemodynamics after endovascular treatment of vascular malformation measured by time-resolved spectroscopy.

Although endovascular treatment has a high success rate, it is not clear how endovascular treatment affects cerebral perfusion and hemodynamics during the perioperative period. We evaluated changes in cerebral blood oxygenation (CBO) repeatedly after endovascular treatment employing time-resolved spectroscopy (TRS). We investigated a patient (10 months old, female) who suffered cerebral arteriovenous fistula. Cerebral angiography demonstrated a pial arteriovenous fistula with three feeders (left PICA, SCA, and AICA). TRS demonstrated a decrease of oxyhemoglobin, total hemoglobin, and oxygen saturation associated with an increase of deoxyhemoglobin in all of the regions measured just after embolization, indicating that embolization improved hyperemia caused by the AV shunt. Interestingly, progressive improvement of hyperemia was observed 3 and 8 days after embolization of the feeders. The present study demonstrated that embolization of the feeders caused progressive changes in CBO and hemodynamics during the perioperative period. TRS may be a useful tool for monitoring cerebral blood perfusion changes after endovascular surgery.

Bedside assessment of cerebral vasospasms after subarachnoid hemorrhage by near infrared time-resolved spectroscopy.

We examined the usefulness of near infrared time-resolved spectroscopy (TRS) for detection of vasospasm in subarachnoid hemorrhage (SAH). We investigated seven aneurysmal SAH patients with poor clinical conditions (WFNS grade V) who underwent endovascular coil embolization. Employing TRS, we measured the oxygen saturation (SO(2)) and baseline hemoglobin concentrations in the cortices. Measurements of TRS and transcranial Doppler sonography (TCD) were performed repeatedly for 14 days after SAH. In four of the seven patients, the SO(2) and hemoglobin concentrations measured in the brain tissue of the middle cerebral artery territory remained stable after SAH. However, in three patients, TRS revealed abrupt decreases in SO(2) and total hemoglobin between 5 and 9 days after SAH. Cerebral angiography performed on the same day revealed severe vasospasms in these patients. Although TCD detected the vasospasm in two of three cases, it failed to do so in one case. TRS could detect vasospasms after SAH by evaluating the cortical blood oxygenation.

EC-IC bypass function in Moyamoya disease and non-Moyamoya ischemic stroke evaluated by intraoperative indocyanine green fluorescence angiography.

Indocyanine green (ICG) emits near-infrared fluorescence when it is excited by near-infrared light. The near infrared fluorescence of ICG was applied to the imaging of cerebral vessels during neurosurgical operations such as clipping of aneurysms. In this study, ICG angiography was applied to extracranial-intracranial (EC-IC) bypass surgery to evaluate the hemodynamic changes induced by bypass in moyamoya disease (MD) and non-moyamoya ischemic diseases (non-MD). These patients underwent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We compared the cortical areas where the bypass supplied blood flow between MD and non-MD. ICG angiography clearly demonstrated the bypass blood flow from the anastomosed STA to the cortical vessels including arteries, capillaries, and veins in both MD and non-MD. Interestingly, the anastomosed STA supplied blood flow to a larger cortical area in MD than non-MD. The bypass supplied greater extent of blood flow to the ischemic brain in MD than in non-MD. This difference might be caused by the fact that the perfusion pressure was lower in MD than in non-MD.

Effects of revascularisation on evoked cerebral blood oxygenation responses in stroke patients.

We demonstrated that ischemic strokes exhibit an increase of deoxyhemoglobin during activation. We evaluated the effect of revascu-larization on the abnormal evoked cerebral blood oxygenation (CBO) re-sponses in these patients, employing near-infrared spectroscopy (NIRS). We selected five patients who exhibited an increase of deoxyhemoglobin associated with increases of oxyhemoglobin and total hemoglobin during activation for this study. These patients showed marked reductions of base-line regional cerebral blood flow and cerebrovascular reserve capacity, which were improved 1 week after revascularization. Postoperative NIRS demonstrated that the increase of deoxyhemoglobin during activa-tion was not observed after revascularization. This preliminary study demonstrated that the abnormal evoked-CBO response in ischemic stroke patients could be improved by revascularization.

Hemangiopericytoma arising in the body of the lateral ventricle.

A 65-year-old woman presented with a very rare hemangiopericytoma in the body of the lateral ventricle.Magnetic resonance imaging demonstrated a homogeneously enhancing mass lesion occupying the bilateral medial portions of the body of the lateral ventricle. Cerebral angiography disclosed a vascular-rich tumor, fed mainly by the left lateral posterior choroidal artery. After devascularization of the feeding vessel by endovascular coiling, the patient underwent complete surgical excision of the tumor via an anterior transcallosal approach, followed by radiation therapy, and has thus far been disease-free for 5 years. The present patient represents the first reported case of hemangiopericytoma arising in the body of the lateral ventricle. In this location of hemangiopericytoma, preoperative embolization could provide a promising option in terms of reducing the intraoperative blood loss and achieving total tumor extirpation with minimum damage to the surrounding structures. Since preoperative identification of hemangiopericytomas confers therapeutic advantages,it is important to be aware that they can occur at unusual ventricular sites.

Optical topography can predict occurrence of watershed infarction during carotid endarterectomy: technical case report.

BACKGROUND: The major risk of CEA is perioperative stroke. NIRS can detect ischemic changes during CEA; however, possible watershed-type perfusion defects may not be detected by single-channel NIRS occurring at some distance from the light source. In the present case, we tested the usefulness of optical topography (ie, multichannel NIRS, OT) for this purpose. CASE DESCRIPTION: The patient (64-year-old man) exhibited nonsymptomatic 80% stenosis of the right ICA with normal cerebral perfusion. CEA was performed to prevent cerebral infarction. We used single-channel NIRS and OT for monitoring of perfusion changes during CEA. The optodes of OT were placed on the skull to cover the frontal and parietal lobes on the right side, whereas the sensor of the single-channel NIRS was placed on the right forehead. The single-channel NIRS detected no significant perfusion changes during surgery. However, the OT revealed occurrence of watershed-type perfusion defects in the border region between the right middle and posterior cerebral artery supply areas during cross-clamping of the right internal carotid artery. Postoperative MRI showed an ischemic region which corresponded to the area associated with the perfusion defects. CONCLUSION: OT could detect watershed-type posterior perfusion defects which the single-channel NIRS failed to detect. OT may represent a useful tool for intraoperative monitoring during CEA.

Effects of in situ administration of excitatory amino acid antagonists on rapid microglial and astroglial reactions in rat hippocampus following traumatic brain injury.

OBJECTIVE: Both microglia and astrocytes respond immediately to traumatic brain injury (TBI). The present study was undertaken to examine whether or not excitatory amino acid (EAA) antagonists could attenuate such glial responses. METHODS: EAA antagonists, including the broad spectrum EAA antagonist, kynurenic acid (KYN), specific N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovalerate (AP-5), and AMPA-KA receptor blocker, 6,7-dinitroquinoxaline-2,3-dione (DNQX), as well as the voltage-dependent ion channel blocker, tetrodotoxin (TTX), were administered into the unilateral hippocampus of rats through a dialysis probe for 30 minutes before the induction of unilateral controlled cortical impact injury. The rats were killed 10 minutes after injury and their brains were processed immunohistochemically for OX42 (marker for microglia) and glial fibrillary acidic protein (GFAP; marker for astrocytes). RESULTS: Ten minutes after injury, microglial activation with increased OX42 immuno-reactivity was evident in the entire hemisphere including the hippocampus ipsilateral to the injury side. Similarly, swollen astrocytes with increased GFAP expression could be detected exclusively on the injury side. When KYN was administered in situ before injury, both the rapid microglial and astroglial responses in the hippocampus were significantly attenuated. However, AP-5, DNQX and TTX, the voltage-dependent ion channel blocker, at doses which can inhibit each channel activation, failed to attenuate these glial reactions. DISCUSSION: These findings indicate that massive ionic fluxes and/or concomitantly occurring EAA release may be closely related to the initiation of microglial and astroglial responses following TBI.

Intravenous infusion of calcium antagonist, nicardipine, does not increase intracranial pressure: evaluation in a rat model of transient cerebral ischemia and reperfusion.

OBJECTIVE AND METHOD: Early use of parenteral antihypertensive drugs is recommended in acute ischemic stroke patients suffering hypertensive emergencies. Calcium antagonist has been widely employed, although there is controversy as to whether calcium antagonist can be administered safely to patients with intracranial hypertension. In a rat model of transient cerebral ischemia and reperfusion, we evaluated the effect of the calcium antagonist, nicardipine, on intracranial pressure (ICP). Using spontaneously hypertensive rats (SHRs), focal cerebral ischemia was induced by an intraluminal thread method. ICP was monitored continuously employing an intraparenchymal catheter. The mean arterial blood pressure (MABP) was reduced by infusing nicardipine intravenously. RESULTS: Following 6 hours of transient ischemia and reperfusion, MABP was decreased by about 10 or 20% as compared to the baseline MABP with low-dose or high-dose nicardipine administration, respectively. ICP was significantly increased following reperfusion, although it did not increase further with nicardipine infusion. CONCLUSION: Under conditions where ICP was high following reperfusion, nicardipine reduced blood pressure safely without increasing ICP in rats.

Comparison of blood-oxygen-level-dependent functional magnetic resonance imaging and near-infrared spectroscopy recording during functional brain activation in patients with stroke and brain tumors.

Blood-oxygen-level-dependent contrast functional magnetic resonance imaging (BOLD-fMRI) has been used to perform functional imaging in brain disorders such as stroke and brain tumors. However, recent studies have revealed that BOLD-fMRI does not image activation areas correctly in such patients. To clarify the characteristics of the evoked cerebral blood oxygenation (CBO) changes occurring in stroke and brain tumors, we have been comparing near-infrared spectroscopy (NIRS) and BOLD-fMRI recording during functional brain activation in these patients. We review our recent studies and related functional imaging studies on the brain disorders. In the primary sensorimotor cortex (PSMC) on the nonlesion side, the motor task consistently caused a decrease of deoxyhemoglobin (deoxy-Hb) with increases of oxyhemoglobin (oxy-Hb) and total hemoglobin (t-Hb), which is consistent with the evoked CBO response observed in normal adults. BOLD-fMRI demonstrated robust activation areas on the nonlesion side. In stroke patients, severe cerebral ischemia (i.e., misery perfusion) caused an increase of deoxy-Hb during the task, associated with increases of oxy-Hb and t-Hb, in the PSMC on the lesion side. In addition, the activation volume of BOLD-fMRI was significantly reduced on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side, but it tended to decrease in other areas during the tasks. In brain tumors, BOLD-fMRI clearly demonstrated activation areas in the PSMC on the lesion side in patients who displayed a normal evoked CBO response. However, the activation volume on the lesion side was significantly reduced in patients who exhibited an increase of deoxy-Hb during the task. In both stroke and brain tumors, false-negative activations (i.e., marked reductions of activation volumes) in BOLD imaging were associated with increases of deoxy-Hb, which could cause a reduction in BOLD signal. BOLD-fMRI investigations of patients with brain disorders should be performed while giving consideration to atypical evoked CBO changes.

Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and BOLD contrast functional MRI in stroke patients.

BACKGROUND AND PURPOSE: To evaluate the mechanisms of failure of blood oxygenation level-dependent (BOLD) imaging in stroke, we compared the evoked cerebral blood oxygenation (CBO) responses and activation volumes (AVs) of BOLD functional MRI (fMRI) in chronic stroke patients with moderate and severe cerebral ischemia. METHODS: We measured the evoked CBO responses in the primary sensorimotor cortex (PSMC) by means of near-infrared spectroscopy during contralateral motor tasks. We compared the AV of BOLD-functional MRI in the PSMC on the nonlesion and lesion sides. Single-photon emission computed tomography was used to classify ischemic status as moderate (slight reduction of regional cerebral blood flow and cerebrovascular reserve capacity [CVRC]) or severe (marked reduction of regional cerebral blood flow and CVRC; ie, misery perfusion). RESULTS: In age-matched controls, deoxyhemoglobin concentration decreased with concomitant increases in oxyhemoglobin and total hemoglobin concentrations during activation. The PSMC on the nonlesion side exhibited a normal CBO response pattern. On the lesion side, moderate cerebral ischemia did not affect the CBO response pattern, but severe cerebral ischemia caused an increase of deoxyhemoglobin during the task, associated with increases of oxyhemoglobin and total hemoglobin. Moderate cerebral ischemia induced only a slight reduction of the AV on the lesion side; however, severe cerebral ischemia markedly reduced the AV on the lesion side. The BOLD signal did not change in some areas of the PSMC on the lesion side in severe cerebral ischemia, whereas it tended to decrease in other areas during the tasks. CONCLUSIONS: Misery perfusion caused a marked reduction of the AV on BOLD imaging, associated with an increase of deoxyhemoglobin concentration during activation. BOLD-fMRI investigations of stroke patients should be performed while giving consideration to baseline circulatory status. Functional near-infrared spectroscopy could be an alternative means to assess the CVRC.

[A case of cerebral arteriovenous malformation revealing repeated intranidal hemorrhage accompanying neovascularization after stereotactic radiosurgery].

We report a patient with cerebral arteriovenous malformation (AVM) revealing growing mass lesion after stereotactic radiosurgery. This 12-year-old female presented headache. CT scan showed hematoma at the head of the right caudate nucleus and angiography showed AVM at the site. LINAC-based stereotactic radiosurgery was performed with the patient. Twenty-three months after the radiosurgery the patient complained headache and CT scan showed hematoma again at the same site, although angiography did not show AVM. Thirty-five months after the radiosurgery mass lesion with enhancement effect was observed at the site and the mass lesion grew gradually thereafter. Thirty-nine months after the radiosurgery the mass lesion was evacuated. Histological examination revealed fibrotic core and surrounding neovascularized area with hemorrhage. The histology shows a new etiology of growing mass lesion after radiosurgery for AVM.

Intraoperative monitoring of cerebral blood oxygenation and hemodynamics during extracranial-intracranial bypass surgery by a newly developed visible light spectroscopy system.

BACKGROUND: Cerebrovascular reconstruction procedures run the risk of changing the balance between oxygen supply and consumption during surgery. We assessed the value of visual light spectroscopy for detecting changes in cerebral blood oxygenation (CBO) during superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. METHODS: We developed a VLS monitoring system which permits continuous monitoring of CBO changes during surgery. Using the VLS, we evaluated the CBO changes in the MCA territory on the lesion side in 18 patients who underwent STA-MCA anastomosis. RESULTS: Temporary occlusion of the MCA (M4 portion) did not change the CBO in 17 patients. However, in the patient with dissecting aneurysm, it caused decreases of oxyhemoglobin and cortical oxygen saturation (CoSo(2)) associated with an increase of deoxyhemoglobin, although these CBO changes were normalized by STA blood flow. In 5 patients, STA blood flow increased the oxyhemoglobin and CoSo(2) and decreased the deoxyhemoglobin, indicating that cortical blood flow (CoBF) was increased. The CoSo(2) before anastomosis was significantly low in the patients who showed an increase of CoSo(2) by STA blood flow (63.0% +/- 2.5%) as compared with those who did not (72.0 +/- 6.1%, P = .024). CONCLUSION: Temporary occlusion of a cortical artery during bypass surgery did not affect the CBO in patients who had chronic cerebral ischemia, but caused acute ischemia in the patient who did not. STA blood flow increased the CoBF during surgery more frequently in patients who showed a low perfusion pressure. The VLS monitoring system is considered useful for evaluating bypass function and facilitates safe and accurate bypass surgery.

Tissue plasminogen activator extravasated through the cerebral vessels: evaluation using a rat thromboembolic stroke model.

Neurotoxic effects of endogenous tissue plasminogen activator (tPA) have recently been reported. Employing a rat model of thromboembolic stroke, we evaluated the extent and degree of extravasation of exogenous tPA administered for the purpose of fibrinolysis. In a thromboembolic model using Sprague-Dawley rats, focal cerebral ischemia was induced at the territory of the middle cerebral artery (MCA). Early reperfusion was induced by administering tPA (10 mg/kg) intravenously at 30 minutes after the onset of ischemia. Extravasated tPA was evaluated by immunohistochemistry, and the concentration of tPA in the brain tissue was quantified by enzyme-linked immunosorbent assay methods. The integrity of the blood-brain barrier (BBB) was examined electronmicroscopically. In a thread model of transient ischemia, reperfusion was induced without tPA administration at 30 minutes or 2 hours after the onset of ischemia, and the tPA content of the brain was quantified. In the rats with thromboembolic stroke, extravasation of tPA was observed at the territory of the MCA. Both the endogenous and exogenous tPA contents were 3.5 +/- 1.6 ng/ml of homogenized brain in saline. Electronmicroscopically, mild ischemic changes were observed, although the integrity of the BBB was preserved. In the thread model rats, the endogenous tPA contents of the ischemic hemisphere were 0.9 +/- 0.1 and 1.0 +/- 0.2 ng/ml in the 30-minute and 2-hour ischemia groups, respectively, and were significantly lower than the tPA contents in the thromboembolic stroke rats (p<0.01). The present findings indicate that significant extravasation of exogenous tPA occurs through the cerebral vessels even though early reperfusion is induced.

Sagittal magnetic resonance imaging of intramural hematoma from non-traumatic dissection of the anterior cerebral artery. Case report.

A 46-year-old woman presented with non-traumatic anterior cerebral artery dissection manifesting as sudden onset of headache and motor weakness of the right lower limb. Angiography revealed luminal narrowing of the left anterior cerebral artery from the A(3) portion to the distal portion. Sagittal T(1)-weighted magnetic resonance imaging showed hyperintensity due to an intramural hematoma around the flow void signal of the affected anterior cerebral artery. Sagittal magnetic resonance imaging should be performed in suspected cases of anterior cerebral artery dissection to detect the diagnostic finding of intramural hematoma.

Attenuation of extravasation of tissue plasminogen activator by the free radical scavenger, edaravone: evaluation in a rat thromboembolic stroke model.

OBJECTIVES AND METHODS: Deleterious effects of tissue plasminogen activator (tPA) have been described recently in experimental studies. For example, tPA can aggravate ischemic neuronal damage through its proteolytic activity. The present study was undertaken to examine whether or not the free radical scavenger, edaravone, could prevent the extravasation of tPA administered for the purpose of fibrinolysis in a rat model of thromboembolic stroke. RESULTS: Significant amounts of tPA were extravasated through the cerebral vessels even when early recanalization was induced by administering tPA at 30 minutes after the onset of schema. Edaravone significantly attenuated such extravasation of tPA. CONCLUSION: In acute ischemic stroke patients, combination therapy using tPA with edaravone appears to be a reasonable strategy for diminishing the negative effects of tPA.

Evaluation of extracranial-intracranial arterial bypass function by using near-infrared spectroscopy.

OBJECT: It has been reported that extracranial-intracranial (EC-IC) arterial bypass surgery can be useful in preventing stroke in patients with hemodynamic compromise. Little is yet known, however, regarding the extent to which the bypass contributes to maintaining adequate cerebral blood oxygenation (CBO) and its temporal changes following surgery. The authors evaluated bypass function repeatedly by using near-infrared spectroscopy (NIRS) after surgery. METHODS: The authors investigated 30 patients who had undergone EC-IC bypass surgery. Single-photon emission computerized tomography revealed a decrease in regional cerebral blood flow (rCBF) and a lowered rCBF response to acetazolamide. Changes in CBO were evaluated in the sensorimotor cortex during compression of the anastomosed superficial temporal artery (STA). When decreases in oxyhemoglobin (HbO2) and total hemoglobin (Hb) concentrations were observed, the bypass was considered to have maintained CBO in the sensorimotor cortex given that decreases in HbO2 and total Hb indicate cerebral ischemic changes. The bypass maintained CBO immediately after surgery in 36.7% of patients (Group I, 11 patients) and at some time after surgery, mostly within 1 year, in 43.3% of patients (Group II, 13 patients); however, it did not maintain it throughout the follow-up period in 20% of patients (Group III, six patients). Note that the preoperative rCBF in patients in Groups I and II was lower than that in patients in Group III (p < 0.004). In fact, the preoperative rCBF predicted whether a bypass would maintain CBO at a cutoff value of 24.5 to 25 ml/100 g/min. Among Groups I and II, 18 patients demonstrated an increase in deoxyhemoglobin during STA compression. The preoperative rCBF in these cases was lower than that in the six remaining patients (p < 0.006). Note that the preoperative rCBF predicted the postoperative deoxyhemoglobin response at a cutoff value of 22.2 to 24 ml/100 g/min. CONCLUSIONS: The EC-IC bypass surgery can maintain CBO immediately after surgery or gradually within 1 year when the preoperative rCBF is below 24.5 to 25 ml/100 g/min. Furthermore, bypass flow plays a critical role in maintaining an adequate CBO when preoperative rCBF is below 22.2 to 24 ml/100 g/min.

Reduction of infarction volume by bolus injection of pamiteplase, a modified tissue plasminogen activator with a longer half-life.

Using a rat model of thromboembolic stroke we evaluated whether or not fibrinolysis by bolus injection of pamiteplase, a modified tissue plasminogen activator (tPA) with a longer half-life, reduces infarction volume. Infarction volume was significantly reduced by the early administration of pamiteplase at 2 h after the onset of ischemia. Hemorrhagic infarction was observed only in 3 of 10 rats (30%) treated at 6 h. Thus, bolus injection of pamiteplase can reduce infarction volume suppressing the incidence of hemorrhage.