Advanced magnetic resonance imaging findings of cerebellar hemangioblastomas: A report of three cases and a literature review.

On conventional magnetic resonance imaging (MRI), hemangioblastomas typically appear as mural nodules with an adjacent surrounding cyst or a solid mass in the cerebellum. However, hemangioblastomas sometimes cannot be reliably distinguished using this imaging technique from other tumors, especially pilocytic astrocytomas and metastatic tumors, because of their similar imaging findings and locations. Herein, we report three cases of cerebellar hemangioblastomas and review their findings on conventional and advanced MRI, including diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI), and magnetic resonance spectroscopy (MRS). Solid contrast-enhanced lesions of hemangioblastomas showed increased apparent diffusion coefficient values on DWI, increased relative cerebral blood volume ratio on DSC-PWI, and high lipid/lactate peak on MRS. Therefore, advanced MRI techniques can be helpful in understanding the pathological and metabolic changes of hemangioblastomas and may be useful for their characterization.

Utility of 3T single-voxel proton MR spectroscopy for differentiating intracranial meningiomas from intracranial enhanced mass lesions.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) provides structural and metabolic information that is useful for the diagnosis of meningiomas with atypical radiological appearance. However, the metabolite that should be prioritized for the diagnosis of meningiomas has not been established. PURPOSE: To evaluate the differences between the metabolic peaks of meningiomas and other intracranial enhanced mass lesions (non-meningiomas) using MR spectroscopy in short echo time (TE) spectra and the most useful metabolic peak for discriminating between the groups. MATERIAL AND METHODS: The study involved 9 meningiomas, 22 non-meningiomas, intracranial enhancing tumors and abscesses, and 15 normal controls. The ranking of the peak at 3.8 ppm, peak at 3.8 ppm/Creatine (Cr), ß-γ Glutamine-Glutamate (bgGlx)/Cr, N-acetyl compounds (NACs)/Cr, choline (Cho)/Cr, lipid and/or lactate (Lip-Lac) at 1.3 ppm/Cr, and the presence of alanine (Ala) were derived. The metabolic peaks were compared using the Mann-Whitney U test. ROC analysis was used to determine the cut-off values for differentiating meningiomas from non-meningiomas using statistically significant metabolic peaks. RESULTS: The ranking of the peak at 3.8 ppm among all the peaks, peak at 3.8 ppm/Cr, bgGlx/Cr, Lip-Lac/Cr, and the presence of Ala discriminated meningiomas from non-meningiomas with moderate to high accuracy. The highest accuracy was 96.9% at a threshold value of 3 for the rank of the peak at 3.8 ppm. CONCLUSION: A distinct elevated peak at 3.8 ppm, ranked among the top three highest peaks, allowed the detection of meningiomas.

Relationship between Postmenopausal Estrogen Deficiency and Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is one of the most severe forms of stroke, which results from the rupture of a cerebral aneurysm. SAH is the only type of stroke with a female predominance, suggesting that reproductive factors may play a significant role in the etiology. Estrogen has important effects on vascular physiology and pathophysiology of cerebral aneurysm and SAH and, thus, potential therapeutic implications. There have been growing bodies of epidemiological and experimental studies which support the hypothesis of a significant relationship between estrogen deficiency and cerebral aneurysm formation with subsequent SAH. This hypothesis is the focus of this review as well as possible pathology-based therapeutics with regard to aspects of molecular pathophysiology, especially related to women's health.

The autotaxin-lysophosphatidic acid-lysophosphatidic acid receptor cascade: proposal of a novel potential therapeutic target for treating glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system (CNS). Its prognosis is one of the worst among all cancer types, and it is considered a fatal malignancy, incurable with conventional therapeutic strategies. As the bioactive multifunctional lipid mediator lysophosphatidic acid (LPA) is well recognized to be involved in the tumorigenesis of cancers by acting on G-protein-coupled receptors, LPA receptor (LPAR) antagonists and LPA synthesis inhibitors have been proposed as promising drugs for cancer treatment. Six LPARs, named LPA1-6, are currently recognized. Among them, LPA1 is the dominant LPAR in the CNS and is highly expressed in GBM in combination with the overexpression of autotaxin (ATX), the enzyme (a phosphodiesterase, which is a potent cell motility-stimulating factor) that produces LPA.Invasion is a defining hallmark of GBM. LPA is significantly related to cell adhesion, cell motility, and invasion through the Rho family GTPases Rho and Rac. LPA1 is responsible for LPA-driven cell motility, which is attenuated by LPA4. GBM is among the most vascular human tumors. Although anti-angiogenic therapy (through the inhibition of vascular endothelial growth factor (VEGF)) was established, sufficient results have not been obtained because of the increased invasiveness triggered by anti-angiogenesis. As both ATX and LPA play a significant role in angiogenesis, similar to VEGF, inhibition of the ATX/LPA axis may be beneficial as a two-pronged therapy that includes anti-angiogenic and anti-invasion therapy. Conventional approaches to GBM are predominantly directed at cell proliferation. Recurrent tumors regrow from cells that have invaded brain tissues and are less proliferative, and are thus quite resistant to conventional drugs and radiation, which preferentially kill rapidly proliferating cells. A novel approach that targets this invasive subpopulation of GBM cells may improve the prognosis of GBM. Patients with GBM that contacts the subventricular zone (SVZ) have decreased survival. A putative source of GBM cells is the SVZ, the largest area of neurogenesis in the adult human brain. GBM stem cells in the SVZ that are positive for the neural stem cell surface antigen CD133 are highly tumorigenic and enriched in recurrent GBM. LPA1 expression appears to be increased in these cells. Here, the author reviews research on the ATX/LPAR axis, focusing on GBM and an ATX/LPAR-targeted approach.

Neuroendoscopic surgery for ventriculitis and hydrocephalus after shunt infection and malfunction: Preliminary report of a new strategy.

If not controlled in the early stage, ventriculitis is difficult to treat neurosurgically and can lead to serious sequelae, a long course of treatment, and hospitalization. We report two cases of ventriculitis and progressive hydrocephalus after shunt infection. Both were successfully treated by neuroendoscopic septostomy in combination with thorough intraventricular irrigation through a single burr hole followed by single shunt revision. Although surgical intervention has not been established as a first-choice treatment for ventriculitis, including early-stage ventriculitis, prompt neuroendoscopic surgery appears effective for the management of ventriculitis and hydrocephalus after shunt infection. The strategy described in this report might be useful to avoid recurrent shunt infections and malfunctions, simplify a shunt, and reduce the overall duration of hospitalization.

Traumatic vertebral artery dissection and cerebral infarction following head and neck injury with a lucid interval.

Cases: Two patients with cerebral infarction following head and neck injury who showed a lucid interval are presented. Outcome: A 70-year-old male showed infarctions in the cerebellum bilaterally and the right hypothalamus on the sixth day after an injury with no fracture of the cervical spine, and bilateral dissection of the vertebral arteries was diagnosed. A 74-year-old male showed infarctions in the territory of the right posterior cerebral artery and posterior inferior cerebellar artery 2 days after injury with fractures of the cervical spine (C2 and C3) and was diagnosed as having artery-to-artery embolism based on dissection of the right vertebral artery. Conclusion: Head and neck injury is a very common presentation in the emergency department. Three-dimensional computed tomography angiography is an effective screening imaging method for vertebral artery dissection that should be carried out on arrival in every patient with fracture of the cervical spine, and even considered in doubtful cases with no fracture.

Auditory dysfunction in patients with cerebrovascular disease.

Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked.

Chronic subdural hematoma in patients over 90 years old in a super-aged society.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgical practice, particularly among aged patients. With the continuing increase in the aged population, further increases in incidence are expected. However, few studies have focused on CSDH in super-aged patients over 90 years old. METHODS: We retrospectively reviewed medical records for 20 consecutive patients over 90 years old with CSDH treated in our department between 2007 and 2013. The diagnosis of CSDH was confirmed by computed tomography (CT). Patients were divided into a surgery group and a conservative group. Surgical procedures included burr-hole surgery followed by insertion of a subdural drain under local anesthesia. Clinical data were compared and analyzed. Neurological status was evaluated according to the modified Rankin Scale at three time points: before suffering from CSDH; at the time of referral or admission to our department; and at discharge or 1 month after the first referral. Statistical tests were used to analyze data and values of P < 0.05 were considered significant. RESULTS: Mean age for the 20 cases was 92.6 years (range, 90 - 96 years). The leading symptoms in this population were hemiparesis and gait disturbance, followed by disturbance of consciousness and speech disturbance. Twelve patients underwent burr-hole surgery. Mean maximum thickness of subdural hematoma as measured on CT was significantly higher in the surgery group (28.2 ± 5.4 mm) than in the conservative group (17.0 ± 3.8 mm; P < 0.01). Postoperatively, mean neurological status was significantly improved in the surgery group (P < 0.01). After surgery, 66.7% of patients could return home directly from hospital. No significant perioperative complications directly related to surgery were encountered in the surgery group, except for transient postoperative restlessness and bruising of extremities due to falls. CONCLUSIONS: Surgery for CSDH is safe and positively recommended even in super-aged patients over 90 years old if the patient's physical status is fair. Pre-illness status is the most important factor for considering operative indications and represents a limiting factor for postoperative outcomes in this age population.

Ruptured aneurysm at the fenestration of the middle cerebral artery detected by magnetic resonance angiography in a patient with systemic lupus erythematosus and renal failure: a case report.

INTRODUCTION: A cerebral aneurysm arising at the fenestration of the middle cerebral artery is extremely rare, with one report describing subarachnoid hemorrhage due to this type of lesion. There have been no reports of this type of lesion occurring in a patient with systemic lupus erythematosus. CASE PRESENTATION: A 47-year-old Japanese woman with 23 years' history of systemic lupus erythematosus and chronic renal failure had sudden onset of subarachnoid hemorrhage. We avoided using contrast medium due to her chronic renal failure. Magnetic resonance angiography showed her ruptured aneurysm arising at the site of fenestration of her middle cerebral artery. Successful clipping, perioperative management avoiding the cerebral vasospasm, renal dialysis initiated after the acute phase and placement of a ventriculoperitoneal shunt were performed, and she was discharged home with no complications. CONCLUSIONS: This is the first report of ruptured aneurysm associated with middle cerebral artery fenestration in a patient with systemic lupus erythematosus as detected by magnetic resonance angiography. The presence and anatomical relationship of fenestration accompanied by aneurysm could be noninvasively and accurately evaluated preoperatively using three-dimensional time-of-flight magnetic resonance angiography with the volume rendering method in a case in which contrast medium was contraindicated.

Primary Central Nervous System Lymphoma of the Cerebellopontine Angle That Initially Occurred as Neurolymphomatosis of the Acoustic Nerve.

We report a rare case of a primary central nervous system lymphoma (PCNSL) of the cerebellopontine angle (CPA) with infiltration into the pyramidal tract that initially presented as neurolymphomatosis (NL) of the acoustic nerve. A 60-year-old male suffered from right-side deafness and was referred to an otolaryngologist. Magnetic resonance imaging (MRI) showed fusiform enlargement of the right acoustic nerve with a hyperintense signal on a T2-weighted image (T2WI) and with gadolinium (Gd) enhancement, without an evidence of parenchymal CNS involvement. Although he was treated with steroids, his symptoms deteriorated. MRI was performed again and showed the mass lesion at the right CPA with enhancement. In addition to this, a lesion with slightly high intensity on a T2WI with Gd enhancement was observed along the right pyramidal tract. Despite steroid pulse therapy, the lesion rapidly progressed. We performed a tumor biopsy, and the histological diagnosis was diffuse large B-cell lymphoma. Pelvic, abdominal, and chest computed tomography scans, gallium cintigraphy, and bone marrow biopsy failed to detect any other evidence of lymphomatous involvement of other organs. We attempted high-dose methotrexate therapy (3.5 g/m2). We found a discrepancy in the therapeutic effect between the CPA lesion and the infiltrated lesion along the pyramidal tract; the lesions were chemo-resistant and chemo-sensitive, respectively. After completion of the second courses of chemotherapy, we began radiotherapy (total dose: 36 Gy). Four months after radiotherapy, the CPA tumor completely disappeared. Thirty-three months after the biopsy, he is doing well with a normal daily life and no signs of recurrence.

Hydrocephalus with panventricular enlargement as the primary manifestation of neurosarcoidosis: a case report.

INTRODUCTION: Hydrocephalus is very uncommon in neurosarcoidosis. To date, there have been only five reported cases of hydrocephalus occurring as the first manifestation of neurosarcoidosis. Such a presentation in a previously healthy patient is challenging to diagnose. CASE PRESENTATION: A 31-year-old Japanese man who had no relevant past history other than sinusitis was admitted to our institution complaining of low-grade fever and mild headache. He was alert and neurologically intact. No respiratory symptoms were observed. Laboratory examination revealed mild elevation of erythrocyte sedimentation rate and serum CD4/CD8 ratio. Serum angiotensin-converting enzyme level was in the normal range. His cerebrospinal fluid showed mild pleocytosis and increased protein level. A chest X-ray revealed bihilar lymphadenopathy with normal lung parenchyma. Computed tomography of his head showed remarkable hydrocephalus with dilatation of all ventricles, particularly the fourth. Gadolinium-enhanced magnetic resonance imaging demonstrated leptomeningeal millet seed-like enhancement and multiple small enhancing lesions along the Virchow-Robin spaces. These findings strongly suggested a chronic inflammatory disease such as neurosarcoidosis. To treat the hydrocephalus, a ventriculoperitoneal shunt was inserted. The postoperative course was satisfactory. After surgery, nasal and skin biopsies were performed and pathological analysis revealed non-caseating granulomas consistent with sarcoidosis. The findings of gallium scintigraphy also supported the diagnosis of sarcoidosis. We obtained the definitive diagnosis of sarcoidosis 3 weeks after admission from the pathological findings by the nasal and skin biopsies, and corticosteroid therapy was started after that. CONCLUSION: We present a rare case of neurosarcoidosis manifesting as acute hydrocephalus with dilatation of all ventricles, particularly the fourth. As hydrocephalus due to neurosarcoidosis has high morbidity and mortality, early diagnosis and proper treatment are particularly important.

Usefulness of 320-row area detector computed tomography for the diagnosis of cystic falx meningioma.

We present a case of cystic falx meningioma. Cystic meningioma is rare and not easy to diagnose preoperatively; it is often misdiagnosed as other tumors, including glial or metastatic tumors with cystic or necrotic changes. This study showed the potential impact of 320-row computed tomography (CT) on image-based diagnostic evaluation of cystic meningioma with special attention to the novel techniques of 4-dimensional CT angiography (4D-CTA) and CT whole-brain perfusion (CTP). 4D-CTA showed the arterial supply feeding the tumor and late enhancement of the tumor nodule, similar to that seen in meningioma by conventional angiography. CTP showed that the tumor had a higher cerebral blood flow and cerebral blood volume and a longer mean transit time than adjacent brain tissue. These findings were consistent with meningioma and reinforced the other imaging findings, resulting in the correct preoperative diagnosis. The new techniques available for 320-row CT can potentially be used to improve differential diagnosis and preoperative assessment of cystic tumors with nodules.

Emergency superficial temporal artery to middle cerebral artery bypass after intravenous recombinant tissue plasminogen activator administration for acute cerebral ischemia in a patient with moyamoya disease.

There are few study data to help in the decision whether to perform aggressive surgical revascularization, such as emergency bypass, after intravenous recombinant tissue plasminogen activator (rt-PA) administration in patients with progressive symptoms due to acute cerebral ischemia. A 33-year-old healthy male with no known previous medical history developed right hemiparesis and motor aphasia. No acute lesion was observed on admission computed tomography. According to the treatment protocol, emergency intravenous rt-PA administration was indicated within 3 h. After rt-PA administration, symptoms progressed to complete right hemiplegia. Emergency magnetic resonance imaging (MRI) showed an acute ischemic lesion in the left basal ganglia. MR angiography showed severe stenosis of the bilateral terminal portion of the internal carotid artery and occlusion of the left middle cerebral artery (MCA). Obvious diffusion-perfusion mismatch was detected. We performed digital subtraction angiography and diagnosed this condition as acute cerebral ischemia induced by moyamoya disease. We decided to perform emergency superficial temporal artery (STA)-MCA bypass to prevent further damage. The operation began 7 h after the administration of rt-PA and successful bypass was achieved. Symptoms stabilized and improved postoperatively. The majority of the area with preoperative hypoperfusion was rescued. Four months after surgery, the patient resumed his previous employment and continues to do well after 1.5 years of follow-up. This is the first report of emergency STA-MCA bypass performed after intravenous rt-PA administration for acute cerebral ischemia in a patient with moyamoya disease. We conclude that emergency STA-MCA bypass is a viable option for patients with moyamoya disease even after administration of rt-PA.

Application of phase sensitive imaging (PSI) for hemorrhage diagnosis in pituitary adenomas.

OBJECTIVE: Intratumoral hemorrhaging is a common occurrence in pituitary adenomas. Asymptomatic pituitary apoplexies have become more frequently diagnosed due to recent advances in magnetic resonance (MR) imaging. The purpose of this study was to investigate the usefulness of phase sensitive imaging (PSI) in the diagnosis of hemorrhages within pituitary adenomas. PATIENTS AND METHODS: PSI methodology was applied to 28 patients with surgically diagnosed pituitary macroadenomas, and compared with conventional methods. No patients presented with sudden onset of apoplectic symptoms. A 3.0 T MR unit was used to examine all patients before surgery. RESULTS: Seventeen of 28 cases exhibited a hemorrhage component on PSI. However, hemorrhaging was demonstrated in 13 of 28 cases by T2-weighted imaging (T2WI). Hemorrhaging was detected in pituitary adenomas by PSI, but not by T2WI, in four of 17 cases. Poor visualization of the hemorrhage in the sellar turcica was a drawback, which was due to PSI artifacts. CONCLUSION: We suggest that PSI be used to provide diagnostic assistance for pituitary apoplexies.

Cerebral ischemia promotes rich pseudopalisading necrosis in the rat c6 glioblastoma model.

The effect of hypoxia on glioma growth including pathological changes was investigated in an experimental model of brain ischemia in the rat C6 glioma model. C6 glioma cells were inoculated into the subcortex of adult Wistar rats. Focal cerebral ischemia near the implanted glioma area was induced by permanent middle cerebral artery occlusion (PMCAO). Ten days later, the rats were sacrificed to compare tumor volume of C6 glioma without PMCAO (control group) versus C6 glioma with PMCAO (hypoxia group). The histological features were also observed. The mean tumor volume in the hypoxia group was significantly larger than that in the control group. The most prominent histological finding in the hypoxia group was abundant formation of pseudopalisading around the necrotic areas. Immunohistological examinations showed intensive staining for vascular endothelial growth factor and hypoxia-inducible factor in these pseudopalisading cells. These findings suggest that cerebral ischemia positively modulates glioma mass growth by the formation of pseudopalisading necrosis, a characteristic histological finding of glioblastoma.

Reversible cortical auditory dysfunction caused by cerebral vasospasm after ruptured aneurysmal subarachnoid hemorrhage and evaluated by perfusion magnetic resonance imaging. Case report.

A 52-year-old woman developed subarachnoid hemorrhage (SAH) caused by a ruptured right internal carotid artery (ICA) aneurysm. Because of the aneurysm configuration, the authors decided to delay surgery and instead undertook serial imaging studies of the aneurysm. The patient remained alert but developed acute bilateral deafness on Day 7. Audiological examination and auditory brainstem responses suggested that the hearing disturbance was cortical in origin. Three-dimensional computed tomography (CT) angiography showed severe vasospasm in the right middle cerebral artery (MCA) and moderate vasospasm in the left ICA and MCA. Three-tesla magnetic resonance (MR) imaging was performed 2 days after the onset of symptoms. Diffusion-weighted and T2-weighted MR images showed an acute infarction in the right insular cortex caused by vasospasm. Perfusion-weighted MR imaging, particularly mean transit time mapping, revealed hypoperfusion in both temporal lobes including the auditory cortex and right auditory radiation. The vasospasm was treated with induction of mild hypertension and hypervolemia. Follow-up MR images, 3D CT angiograms, and audiometry performed 2 weeks after the first examination showed recovery of vasospasm and resolution of perfusion abnormality and hearing disturbance. On Day 26, the aneurysm was successfully occluded with clips and the patient was discharged with no deficits. To the authors' knowledge, this is the first reported case of reversible cortical auditory dysfunction purely due to bilateral cerebral vasospasm detected using perfusion MR imaging after SAH.

Relationship of hypotension and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Changes in systemic arterial blood pressure and the degree of cerebral vasospasm were investigated in 125 patients with aneurysmal subarachnoid hemorrhage. METHODS: Systemic arterial blood pressure was measured every 2 hours in each patient for a period of more than 2 weeks, and a fall in systemic blood pressure (FBP) was defined as a decrease of >40 mmHg of systolic blood pressure between two consecutive measurements. RESULTS: A total of 91 FBPs occurred in 52 (41.6%) of 125 patients despite specific post-operative management to prevent hypovolemia. Five (5.5%) of the 91 FBPs occurred just before the onset of symptomatic vasospasm. Symptomatic vasospasm was observed in 36 (69.2%) of 52 patients with FBP and in 32 (43.8%) of 73 patients without FBP (p<0.01, chi-squared test). A hypodense area on computed tomographic scans in association with cerebral vasospasm was observed in 25 (48.1%) of 52 patients with FBP and in 21 (28.8%) of 73 patients without FBP (p<0.05). DISCUSSION: We conclude that FBP might result from delayed cerebral vasospasm and/or brain dysfunction owing to subarachnoid hemorrhage itself.

Surgical treatment of arteriovenous malformation in a patient with human immunodeficiency virus infection and hemophilia a: case report.

This case illustrates surgical treatment of an arteriovenous malformation (AVM) in a patient with hemophilia A also infected with human immunodeficiency virus (HIV). A 31-year-old man was admitted to our hospital with right parietal intracerebral hemorrhage. He had previously been diagnosed with hemophilia A and HIV. Carotid angiography revealed an AVM. As the hematoma enlarged and clinical symptoms progressed, we resected the hematoma and the AVM while providing supplemental infusion of Factor VIII before, during, and after the operation. The patient did not experience abnormal postoperative bleeding, and he was discharged with mild motor weakness of the left lower extremity. We discuss the surgical indications, risk, and patient management in relation to hemophilia and HIV infection.

Spatial resolution of calpain-catalyzed proteolysis in focal cerebral ischemia.

Transient forebrain ischemia induces calpain-mediated degradation of the neuronal cytoskeleton, alpha-fodrin, and this results in ischemic neuronal death. In this study, we investigated the spatial distribution and temporal changes of calpain-catalyzed alpha-fodrin proteolysis in focal cerebral ischemia and examined the effects of a calpain inhibitor. Ischemia was induced in gerbils by 3-h middle cerebral artery occlusion followed by reperfusion. Animals were divided into four groups: a sham-operated group, an ischemic group, a vehicle-treated group, and a calpain inhibitor-treated group. Intravenous injections of vehicle or calpain inhibitor I were administered 30 min before ischemia. Infarct volumes were measured 1 day after reperfusion and the spatial distribution of calpain-catalyzed alpha-fodrin proteolysis was investigated by immunohistochemistry 15 min, 1 h, 4 h, and 1 day after reperfusion. Infarct volume (mean +/- SD) in the ischemic group and the vehicle-treated group was 204.6 +/- 19.1 mm3 and 212.4 +/- 16.3 mm3, respectively, and the calpain inhibitor I reduced the infarct volume [149.4 +/- 25.2 mm3 (P < 0.05)]. Immunoblot analysis demonstrated that calpain inhibitor reduced proteolysis. Ischemia induced fodrin proteolysis in the ischemic core and the peri-infarct zone within 15 min after reperfusion, with proteolysis developing quickly in the ischemic core and more slowly in the peri-infarct zone. Proteolysis preceded neuronal death in the peri-infarct zone. Calpain inhibitor I ameliorated neuronal death in the peri-infarct zone but not in the ischemic core. Thus, calpain plays a pivotal role on focal ischemia as well as in global ischemia.

A non-enzymatic derived arachidonyl peroxide, 8-iso-prostaglandin F2 alpha, in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage participates in the pathogenesis of delayed cerebral vasospasm.

We performed serial measurements of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a non-enzymatic derived arachidonyl peroxide, in the cerebrospinal fluid (CSF) of 34 patients with subarachnoid hemorrhage (SAH). Patients were treated with open or endovascular surgery within 48 h of onset. Delayed cerebral vasospasm was verified by the presence of a low-density area on CT scan indicating focal cerebral infarction occurring after symptomatic delayed vasospasm. Concentrations of 8-iso-PGF2alpha in the CSF of 15 patients exhibiting delayed cerebral vasospasm were compared with those of 19 patients who did not exhibit vasospasm. The concentrations of 8-iso-PGF2alpha in the CSF of patients showing vasospasm were 42.4+/-37.1 pg/ml (mean+/-S.D., n=12) on Days 0-2, 66.4+/-41.0 pg/ml (n=14) on Days 3-5, 118.5+/-89.9 pg/ml (n=15) on Days 6-8, 86.2+/-70.2 pg/ml (n=11) on Days 9-11, 48.8+/-31.8 pg/ml (n=10) on Days 12-14, 27.8+/-20.1 pg/ml (n=7) after Day 20, while the concentrations in patients not showing vasospasm were 24.8+/-12.0 pg/ml (n=18) on Days 0-2, 25.7+/-15.2 pg/ml (n=19) on Days 3-5, 47.5+/-52.3 pg/ml (n=18) on Days 6-8, 56.7+/-72.0 pg/ml (n=13) on Days 9-11, 34.2+/-53.1 pg/ml (n=15) on Days 12-14, 20.1+/-18.2 pg/ml (n=10) after Day 20. CSF concentrations of 8-iso-PGF2alpha on Days 3-5 and Days 6-8 were significantly higher in patients showing vasospasm as compared to patients not showing vasospasm. CSF levels of 8-iso-PGF2alpha in patients showing vasospasm gradually increased in the days after onset of SAH and peaked on Days 6-8. Levels returned to normal after Day 20. These values on Days 3-5, Days 6-8, and Days 9-11 were significantly higher than the value after Day 20. Considering these data and the biological activities of 8-iso-PGF2alpha, such as development of inflammation, membrane perturbation and vasoconstriction, we conclude that 8-iso-PGF2alpha may play a role in delayed cerebral vasospasm after SAH.