Near-infrared diffuse reflectance signals for monitoring spreading depolarizations and progression of the lesion in a male rat focal cerebral ischemia model.

In ischemic stroke research, a better understanding of the pathophysiology and development of neuroprotection methods are crucial, for which in vivo imaging to monitor spreading depolarizations (SDs) and evolution of tissue damage is desired. Since these events are accompanied by cellular morphological changes, light-scattering signals, which are sensitive to cellular and subcellular morphology, can be used for monitoring them. In this study, we performed transcranial imaging of near-infrared (NIR) diffuse reflectance at ∼800 nm, which sensitively reflects light-scattering change, and examined how NIR reflectance is correlated with simultaneously measured cerebral blood flow (CBF) for a rat middle cerebral artery occlusion (MCAO) model. After MCAO, wavelike NIR reflectance changes indicating occurrence of SDs were generated and propagated around the ischemic core for ∼90 min, during which time NIR reflectance increased not only within the ischemic core but also in the peripheral region. The area with increased reflectance expanded with increase in the number of SD occurrences, the correlation coefficient being 0.7686 (n = 5). The area with increased reflectance had become infarcted at 24 hr after MCAO. The infarct region was found to be associated with hypoperfusion or no-flow response to SD, but hyperemia or hypoperfusion followed by hyperemia response to SD was also observed, and the regional heterogeneity seemed to be connected with the rat cerebrovasculature and hence existence/absence of collateral flow. The results suggest that NIR reflectance signals depicted early evolution of tissue damage, which was not seen by CBF changes, and enabled lesion progression monitoring in the present stroke model.

Hydrogen improves neurological function through attenuation of blood-brain barrier disruption in spontaneously hypertensive stroke-prone rats.

BACKGROUND: Enhanced oxidative stress occurs in spontaneously hypertensive stroke-prone rats (SHRSP), and is important in blood-brain barrier (BBB) disruption. Hydrogen can exert potent protective cellular effects via reduction in oxidative stress in various diseases. The present study investigated whether long-term hydrogen treatment can improve neurological function outcome in the SHRSP model, and the effects of hydrogen on BBB function, especially the oxidative stress and the activity of matrix metalloproteinases (MMPs) in this model. Fifty-six animals were randomly assigned to 2 groups and treated as follows: SHRSP treated with hydrogen-rich water (HRW) (HRW group, n = 28); and SHRSP treated with regular water (control group, n = 28). The effect of HRW on overall survival and neurological function, and the effects of HRW on reactive oxygen species, BBB function, and MMP activities were examined. RESULTS: HRW treatment improved neurological function and tended to improve overall survival but without significant difference. The numbers of bleeds and infarcts were lower in the cortex and hippocampus in the HRW group. The HRW group exhibited a significantly lower number of 8-hydroxy-2'-deoxyguanosine-positive cells and vessels of extravasated albumin in the hippocampus compared with the control group. MMP-9 activity was reduced in the hippocampus in the HRW group compared with the control group. CONCLUSIONS: The present study suggests that ingestion of HRW can improve neurological function outcome in the SHRSP model. This beneficial effect may be due to attenuation of BBB disruption via reduction in reactive oxygen species and suppression of MMP-9 activity in the hippocampus.

Feasibility of the combination of 3D CTA and 2D CT imaging guidance for clipping microsurgery of anterior communicating artery aneurysm.

OBJECTIVE: We report the technique of three-dimensional computed tomography angiography (3D CTA)+two-dimensional computed tomographic (2D CT) imaging as an adjunct in early surgery for a ruptured anterior communicating artery (ACoA) aneurysm by adopting an anterior interhemispheric approach. These combined imaging modalities provide accurate intraoperative anatomical information. METHODS: To produce images for an anterior interhemispheric approach, 3D CTA+2D coronal CT images, which are perpendicular to the direction of the surgical approach at three levels (brain surface, genu of the corpus callosum and aneurysm neck), were constructed. We also produced two 3D CTA+2D CT images of the lamina terminalis, with a horizontal 10-degree difference, to clarify the vascular architecture around the aneurysm stereotactically, as well as the dissection point and direction to open the lamina terminalis. Furthermore, we produced a 3D CTA+2D sagittal CT image at the midline, which allowed us to understand the anatomical architecture of the aneurysm, planum sphenoidale and tuberculum sellae. In addition, four different 3D CTA aneurysm images were produced for deciding the clip size preoperatively. RESULTS: The imaging findings in 28 patients with 28 ACoA aneurysms facilitated early clipping. Based on these 3D CTA+2D CT images, we conducted aneurysm surgery, and successfully performed neck clipping via an anterior interhemispheric approach. CONCLUSION: The combination of 3D CTA and 2D CT images is a feasible and useful method of image guidance for ACoA aneurysm microsurgery.

Acute posterior fossa epidural hematoma in a newborn infant with Menkes disease.

Epidural hematoma (EDH) in newborn infants is rare compared with other types of intracranial hemorrhages. Furthermore, posterior fossa EDH is extremely rare. We present a case of posterior fossa EDH in an infant with Menkes disease with accessory bones in the occiput. A male infant with a condition diagnosed with Menkes disease by prenatal testing was born at 39 weeks via vacuum extraction. The patient presented with a mild tremor at 2 days after delivery. A brain computed tomography (CT) scan showed an acute EDH in the posterior fossa, extending into the occipitoparietal area. Three-dimensional CT and bone window CT scan revealed several accessory bones, diastasis of 1 accessory suture, a communicated fracture, and a linear fracture in the occipital bone. Furthermore, a bone fragment from a communicated fracture displaced toward the inside. The patient was treated conservatively for EDH because of his good general condition. The hematoma gradually resolved, and his tremor did not recur. We suggest the following mechanism of posterior fossa EDH development in our patient: (1) external force was applied to the occiput inside the birth canal during delivery, resulting in diastasis; (2) a communicated fracture occurred, and a bone fragment displaced toward the inside (linear fracture was caused indirectly by the force); (3) a transverse sinus was injured by the fragment; and (4) EDH developed in both the posterior fossa and supratentorial region. Copper deficiency can also cause fragility of connective tissues, vessels, and bones.

Sulfasalazine and temozolomide with radiation therapy for newly diagnosed glioblastoma.

BACKGROUND: A recent phase 1/2 clinical trial argued for caution for the use of sulfasalazine in progressive glioblastoma (GBM). However, the study enrolled patients with recurrent or progressive high-grade glioma indicating that patients recruited probably had severe disease. Thus, the study may not accurately reflect the effectiveness of sulfasalazine for GBM and we hypothesized that earlier sulfasalazine administration may lead to anticancer effects. AIM: The aim of this study was to investigate whether sulfasalazine can improve the outcomes of patients with newly diagnosed GBM. SUBJECTS AND METHODS: A total of 12 patients were treated with temozolomide and sulfasalazine with radiation therapy after surgery. Twelve patients with primary GBM treated with temozolomide and radiation therapy formed the control group. Progression-free survival (PFS), overall survival (OS) and seizure-free survival (SFS) curves were obtained using the Kaplan-Meier method. The survival curves were compared using the log-rank test. RESULTS: The median OS, PFS and SFS did not differ between the groups. Grade 3 or 4 adverse events occurred over the duration of the study in nine (75%) patients. The median SFS was 12 months in nine patients who received sulfasalazine administration for more than 21 days, which was strongly but not significantly longer than the 3 months observed in the control group (P = 0.078). CONCLUSIONS: Sulfasalazine treatment with temozolomide plus radiotherapy for newly diagnosed primary GBM is associated with a high rate of discontinuation due to hematologic toxic effects. This treatment may have no effect on OS or PFS, although it may improve seizure control if an adequate dose can be administered.

An analysis of T2 mapping on brain tumors.

PURPOSE: Vasogenic edema on glioblastoma multiforme (GBM) or a metastatic brain tumor (METS) may have different T2 relaxation time values because it involves an increased water component. In this study, we assessed the diagnostic utility of T2 mapping techniques in distinguishing GBM from METS. MATERIALS AND METHODS: We studied a glioblastoma (GBM) patient and a metastatic brain tumor (METS) patient who had not undergone previous surgery or treatment. All MR imaging was carried out using a 3.0-T whole-body unit, and axial T2 maps were generated with five TEs (TE = 20, 40, 60, 80, and 100 ms). Data were analyzed by using image processing and analysis software. RESULTS: The T2 map of a GBM case showed that the -peritumoral area at a T2 relaxation time of 120-160 ms is prominent compared with the area at 210-240 ms. In contrast, the peritumoral area at 210-240 ms was prominent compared with the area at 120-160 ms in a METS case. CONCLUSION: The distribution of T2 relaxation time in the peritumoral area shows different patterns in glioblastomas and metastatic brain tumors.

Evaluation of the stage of hemorrhage using optical diffuse reflectance spectroscopy: an in vivo study.

Intracerebral hemorrhage (ICH) is a common and often fatal subtype of stroke. Estimation of the stage of hemorrhage allows clinicians to know when the hemorrhage occurred, even in unconscious patients, enabling decisions to be made about the optimal management and treatment strategy. After ICH, oxidative denaturation of the hemoglobin progresses, and deoxyhemoglobin is gradually converted to methemoglobin. MRI has been used to estimate the stage of hemorrhage by evaluating the status of hemoglobin. However, there is currently no bedside device that can be used for the measurement of hemoglobin derivatives in patients with hematomas. The aim of the present study was to investigate the validity of using optical diffuse reflectance spectroscopy (ODRS) for bedside evaluation of the stage of hemorrhage. An ICH model was generated in adult Sprague-Dawley male rats by stereotactically injecting 50 µl of autologous blood into the right caudate nucleus. To analyze the hemoglobin derivatives in the hematomas, ODRS measurement was performed for the rats in vivo. In all rats, we found increased absorption at around 630 nm, which indicated the formation of methemoglobin. In conclusion, the results of the present study suggest that ODRS allows clinicians to more easily evaluate the stage of hemorrhage at the patient's bedside.

The effect of hydrogen gas on a mouse bilateral common carotid artery occlusion.

In recent studies, molecular hydrogen selectively reduced the levels of hydroxyl radicals in vitro and exerted a therapeutic anti-oxidant activity in a rat middle cerebral artery occlusion model. The aim of this study was to investigate the effect of hydrogen gas on a mouse bilateral common carotid artery occlusion (BCCAO) model. Male C57BL/6J mice were subjected to transient BCCAO with a nontraumatic aneurysm clip. The mice were divided into three groups: sham, BCCAO, and BCCAO treated with 1.3 % hydrogen gas. Cerebral blood flow (CBF) in the cortex was measured sequentially for both hemispheres with a non--invasive and noncontact laser Doppler blood perfusion imager during the procedure. Vital signs were also recorded. Oxidative stress evaluated by measuring the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), neuronal injury in the hippocampal CA1 sector, and brain water content were assessed 24 h after ischemia. The hydrogen gas treatment had no significant effect on vital signs or CBF values. However, the reduction of the expression of 8-OHdG, the decrease in the neuronal injury in the hippocampal CA1 sector, and the attenuation in brain water content were observed in hydrogen-treated mice. In conclusion, hydrogen gas might be effective in a mouse BCCAO model.

A better mild traumatic brain injury model in the rat.

The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI.

Adiponectin and traumatic brain injury.

Adiponectin, a circulating adipose-derived hormone regulating inflammation and energy metabolism, has beneficial actions on cardiovascular disorders. Recent studies have suggested that adiponectin might be a potential molecular target for ischemic stroke therapy; however, little is known about the effects of adiponectin on traumatic brain injury. The present study examined the immunoactivity of adiponectin.Adult male Sprague-Dawley rats were subjected to lateral fluid percussion injury using the Dragonfly device. Immuno-histochemical studies showed that the adiponectin expression was increased in the cerebral cortex at 24 h after injury and in the hippocampus at 72 h after injury. Our findings suggest that adiponectin might participate in the pathophysiological process occurring after traumatic brain injury.

Traumatic hematoma of the posterior fossa.

Posterior fossa injury is rare, occurring in less than 3 % of head injuries. We retrospectively reviewed patients' clinical and radiological findings, management, and outcomes. The aim of the present study was to investigate the features of posterior fossa hematoma, including posterior fossa epidural hematoma (EDH), posterior fossa subdural hematoma (SDH), and intracerebellar hematoma. From January 1995 to January 2009, 4,315 patients with head trauma were hospitalized at our institution. The -present study focused on 41 patients (1.0 %) with traumatic hematomas of the posterior fossa. Eighteen patients had EDH, 10 patients had SDH, and 17 patients had intracerebellar hematomas. In each type of injury, occipital bone fractures were seen in many patients, and hematoma enlargement was often observed within a few days of the injury. In addition, a high frequency of associated lesions and a high poor outcome rate were features of intracerebellar hematomas and -posterior fossa SDH. The present study suggests that repeat CT imaging and careful management are necessary until the lesion is stabilized, and patients showing lesions with mass effects should therefore be immediately treated with surgery.

Traumatic basal ganglia hematomas: an analysis of 20 cases.

Twenty patients with traumatic basal ganglia hematoma (TBGH) were studied. Of the 20 patients, 16 were male and 4 were female, with an age range of 4-89 years (mean, 54.4 years). The causes of injury were traffic accidents in 12 patients and falls in 8. The mean admission GCS score was 7.5. Skull fractures were revealed in five patients (25 %). The hematoma was found in the putamen in 15 patients (80 %), the thalamus in 4, and the caudate in 1. The mean hematoma volume was 10.7 mL. The CT findings indicated focal contusions in 9 patients, subdural hematoma in 5, intraventricular hemorrhage in 4, subarachnoid hemorrhage in 10, and diffuse axonal injury in 5. Six patients (30 %) underwent surgery. The final outcomes were poor: 7 patients (35 %) died, 1 was in a vegetative state, 4 experienced severe disabilities, and 8 patients (40 %) made a favorable recovery. The statistical analysis identified the GCS score and midline shift as prognostic factors.Our study revealed interesting characteristics of TBGH, including a high frequency of putaminal involvement, a low frequency of skull fractures, a high frequency of associated intracranial lesions, and a high poor outcome and mortality rate.

Cerebrospinal fluid congestion in the perioptic space.

Recent attention has been paid to the -cerebrospinal fluid (CSF) dynamics between the intracranial subarachnoid space (SAS) and the SAS around the optic nerve (ON-SAS). We experienced three patients who had an expanded ON-SAS associated with mass lesions extending into the optic canal, and studied their MRI findings after decompressive surgery. In all three patients, decompressive surgery of the optic canal resulted not only in the disappearance of the expanded ON-SAS, but also in improvement of the visual function. The present study may indicate that normalization of the ON-SAS can be considered to be the achievement of "effective" decompression. Therefore, we suggest that, in patients with an expanded ON-SAS associated with mass lesions, the state of the ON-SAS should be evaluated by pre- and postoperative MRI, in addition to the degree of tumor resection.

Surgical results after primary decompressive craniectomy in poor-grade aneurysmal subarachnoid hemorrhage.

It is well known that patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) have poor outcomes owing to significant mass effect and brain stem compression. On the other hand, decompressive craniectomy (DC) has shown efficacy in reducing morbidity and mortality in patients with intracranial hypertension. Here, we study the efficacy of DC in poor-grade SAH with attention to surgical outcome. A total of 38 consecutive patients with poor-grade SAH was treated in our hospital between 1 August 2005 and 30 July 2010. Among these 38 patients, we involved 15 patients with DC in the present study. We retrospectively reviewed medical charts and radiological findings. Glasgow Outcome Scale score on discharge showed good response in 1 (6.7 %), moderate disability in 6 (40.0 %), severe disability in 4 (28.1 %), vegetative state in 2 (1.3 %), and death in 2 (13.3 %). In particular, 3 grade IV patients (50.0 %) had a favorable outcome. Recent several experimental studies also indicated that DC significantly improves outcome owing to increased perfusion pressure or reduced intracranial pressure. We suggest that the DC provided the efficacy in reducing mortality in poor-grade SAH patients.

Decompressive craniectomy with hematoma evacuation for large hemispheric hypertensive intracerebral hemorrhage.

Hemispheric hypertensive intracerebral hemorrhage (ICH) has a high mortality rate. Decompressive craniectomy (DC) has generally been used for the treatment of severe traumatic brain injury, aneurysmal subarachnoid hemorrhage, and hemispheric cerebral infarction. However, the effect of DC on hemispheric hypertensive ICH is not well understood. To investigate the effects of DC for treating hemispheric hypertensive ICH, we retrospectively reviewed the clinical and radiological findings of 21 patients who underwent DC for hemispheric hypertensive ICH. Eleven of the patients were male and 10 were female, with an age range of 22-75 years (mean, 56.6 years). Their preoperative Glasgow Coma Scale scores ranged from 3 to 13 (mean, 6.9). The hematoma volumes ranged from 33.4 to 98.1 mL (mean, 74.2 mL), and the hematoma locations were the basal ganglia in 10 patients and the subcortex in 11 patients. Intraventricular extensions were observed in 11 patients. With regard to the complications after DC, postoperative hydrocephalus developed in ten patients, and meningitis was observed in three patients. Six patients had favorable outcomes and 15 had poor outcomes. The mortality rate was 10 %. A statistical analysis showed that the GCS score at admission was significantly higher in the favorable outcome group than that in the poor outcome group (P = 0.029). Our results suggest that DC with hematoma evacuation might be a useful surgical procedure for selected patients with large hemispheric hypertensive ICH.

Is decompressive craniectomy a risk factor for ventriculomegaly?

OBJECTIVE: Decompressive craniectomy (DC) is an established therapeutic option following severe traumatic brain injury (TBI). However, several delayed complications of DC have been reported, including ventriculomegaly, which can lead to poor patient outcomes. Nevertheless, ventriculomegaly can occur after TBI even without DC. The aim of the present study was to investigate the influence of DC on ventriculomegaly. MATERIAL AND METHODS: Adult male Sprague-Dawley rats (300-400 g) were subjected to lateral fluid percussion injury using a fluid percussion device. Rats were randomly divided into four groups: sham, craniectomized without trauma (D group), traumatized without DC (FPI group), and craniectomized immediately after trauma (FPI + D group). On day 28 of recovery, ventricular volumes were measured by image analysis. RESULTS: There was no significant difference in ventricular size between the sham group and the D group animals or between the FPI group and the FPI + D group animals. CONCLUSION: These data suggest that DC may not be a risk factor for ventriculomegaly after TBI.

Hydrocephalus following decompressive craniectomy for ischemic stroke.

Numerous studies on hydrocephalus after decompressive craniectomy (DC) for severe traumatic brain injury have been reported, whereas there have been only two reports on DC for hemispheric cerebral infarction. Here, we present the clinical details of 23 patients who underwent DC for hemispheric cerebral infarction and the incidence of hydrocephalus following DC. Of the 23 patients, 13 were male and 10 were female, with an age range from 34 to 75 years (mean, 60.8 years). The areas of hemispheric infarctions were those of the middle cerebral arteries in 12 patients and of the internal carotid arteries in 11 patients. The mean preoperative GCS score was 6. Nineteen patients (82.6 %) underwent cranioplasty. Pre-cranioplasty hydrocephalus was observed in 11 (47.8 %) patients. Four patients who had precranioplasty hydrocephalus were transferred or died without cranioplasty, and post-cranioplasty hydrocephalus occurred in 7 (36.8 %). Only one patient underwent a shunt procedure after cranioplasty. We consider that the explanation for the discrepancies between our study and the previous studies might lie in the definition of hydrocephalus and the indications for shunting.

A suitable formula for estimating the volume gained by decompressive craniectomy in malignant hemispheric infarction.

Decompressive craniectomy (DC) improves the survivability and functional outcome in patients with malignant hemispheric infarction (MHI). The decompressive effect of DC depends on the decompressive volume (DV). The value of the formulas for estimating DV has not been reported to date. We have investigated the value of the formulas to estimate DV in patients with MHI. We analyzed the head CTs of six patients who underwent DC for MHI. We examined 1/2ABC, 1/3ABC, π/6ABC, and 2/3Sh formulas to determine the formula that gives the closest estimation of DV compared with computer-assisted volumetric analysis (gold standard). The mean volume values of the gold standard, 1/2ABC, 1/3ABC, π/6ABC, and 2/3Sh formulas were 100.2, 102.4, 68.3, 105.2, and 109.2 mL respectively. Spearman's correlation coefficient was assessed for DV obtained by each of the four different formulas relative to the gold standard. These were as follows: 1/2ABC = 0.8095 (p < 0.05), 1/3ABC = 0.8095 (p < 0.05), π/6ABC = 0.7381 (p < 0.05), and 2/3Sh = 0.4524 (p > 0.05). In conclusion, the 1/2ABC formula is the most useful and the closest estimation of DV in patients with MHI after DC.

Anterior cerebral artery dissecting aneurysm associated with untreated craniopharyngioma.

Coexistence of cerebral aneurysm and untreated craniopharyngioma is extremely rare. We present an extremely rare case of anterior cerebral artery dissecting aneurysm associated with untreated craniopharyngioma, and discuss the relationship between these two lesions.

L-Leucine induces growth arrest and persistent ERK activation in glioma cells.

Glioma is the most common type of brain tumor, and has the worst prognosis in human malignancy. Experimental evidence suggests that the use of high concentrations of various amino acids may perturb neoplastic cell growth. Thus, the aim of this study was to investigate whether essential amino acids can alter the growth and proliferation of glioma cells. Studies were performed using C6 rat glioma cell lines. High concentration of L-leucine induced growth arrest of glioma cell lines. Terminal transferase uridyl nick end labeling assay and cell cycle analysis showed that the effect of L-leucine on glioma cells growth was not cytotoxic, but rather cytostatic. Additionally, the extracellular signal-regulated protein kinase was activated in L-leucine-treated glioma cells, and inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK) enhanced the effect of L-leucine on glioma cell growth. These data suggest that high concentration L-leucine combined with inhibition of MEK is a potential strategy for glioma cell growth arrest.