The changes of c-Fos expression by motor cortex stimulation in the deafferentation pain model.

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5-3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.

[Leiomyosarcoma of the uterus metastatic to the brain].

A case of 52-year-old female presented with dysarthria and paresis of right upper extremity 3 years after an operation and chemotherapy for uterine leiomyosarcoma. Magnetic resonance imaging showed an enhanced mass in the left corona radiata. Brain biopsy was carried out and pathological examination of the specimen showed features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and its metastasis to the brain is rare. Only 13 other cases have been published. The patient underwent gamma-knife therapy and obtains good quality of life.

Usefulness of acellular dermal graft as a dural substitute in experimental model.

BACKGROUND: Friction injury of cortical surface or cerebrospinal fluid leakage are the major complications of polytetrafluoroethylene (ePTFE) duraplasty because of their strong surface tension and lesser adaptability. Autologous duraplasties are also accompanied by potential donor-site complications and are inappropriate for large defects. Acellular Dermal Graft (ADG), prepared from cadaver human skin, does not have the above-mentioned drawbacks because of its human nature. Moreover, the dermal basement membrane and supporting tissues remain intact, so the rate of cellular migration and transformation to the surrounding host tissue is supposed to be excellent. We studied ADG in canine model to observe the rate of transformation into the surrounding dura mater via collagen synthesis from the invaded fibroblasts to evaluate its usefulness as a duraplasty. METHODS: Dural grafting surgery was performed on 6 adult mongrel dogs weighing from 8 to 12 kgs under general anesthesia. Three dogs were sacrificed after 1 month (acute) of surgery and the other three (chronic) were sacrificed after 3 months with overdose of pentobarbital sodium. Transcardiac perfusion-fixation with 4% paraformaldehyde was done. Hematoxylin-eosin and trichrome masson stains were performed to see the graft cellularity. Thickness of grafts was also assessed along the length of the histologic sections. RESULTS: Duralization, which was microscopically characterized by infiltration with regular array of collagen fibers, was observed at a few places in every high-power field in acute group. But in chronic animals, where dermal side of ADG was facing towards cranium, duralization was excellent. CONCLUSIONS: Our result suggests that ADG can be considered as a useful dural substitute.

Measurement of ankle brachial index for assessment of atherosclerosis in patients with stroke.

BACKGROUND: Though atherosclerosis is generally regarded as a risk factor for stroke, its quantitative assessment in patients with stroke has not yet been reported. Recently, the ankle brachial index (ABI) has been receiving increasing attention as a noninvasive measurement of atherosclerosis. In this study, we investigated ABI to determine the degree of atherosclerosis in patients with stroke. METHODS: ABI was measured in 114 patients who had suffered a stroke, and the significance of differences between the ABI of the stroke subgroups and that of the normal group was investigated. The correlation of ABI with the degree of cerebral artery stenosis was also investigated. RESULTS: There was no significant difference in ABI between the hemorrhagic groups and the normal group, but in the infarction group (p = 0.0002) ABI was significantly less than the normal group. ABI was significantly correlated with the degree of stenosis in the intracranial internal carotid artery and middle cerebral artery (p < 0.0001, respectively). CONCLUSIONS: A strong relationship between ischemic stroke and atherosclerosis was demonstrated quantitatively by ABI measurement. A decrease in ABI may be a risk factor for ischemic stroke.

Assessment of vascular injury in patients with stroke by measurement of pulse wave velocity.

Vascular injury causes various diseases and may be especially important as a risk factor for stroke, and early diagnosis is useful for prevention of stroke. Recently, pulse wave velocity (PWV) has been receiving increasing attention as a noninvasive measurement of vascular injury. In this study, we investigated PWV of patients with stroke to determine the degree of vascular injury. PWV was measured in 114 patients with stroke, and the significance of differences between the PWV of stroke subgroups and that of the control group was investigated in an age- and sex-matched case-control study. In comparison with the control group, PWV was increased significantly in patients with intracerebral hemorrhage (P = .0107) and cerebral infarction (P < .0001). Of risk factors, hypertension and high PWV were independently related to the presence of intracerebral hemorrhage on multivariate analyses. Smoking and high PWV were found to be independent risk factors for cerebral infarction. A strong relationship between stroke and PWV was demonstrated. Measurement of PWV is useful for quantitatively assessing the progression of vascular injury, which may potentially be a risk factor for stroke.

A case of definitely congenital glioblastoma manifested by intratumoral hemorrhage.

BACKGROUND: A female infant was born with a left-sided glioblastoma that manifested clinically with weakened crying and feeding on day 1 of life, fever and bulging anterior fontanel on day 4, and right hemiparesis by day 10. METHODS: Preoperative magnetic resonance imaging showed hemosiderin intensity indicating that hemorrhage had occurred during the prenatal period. Radical surgical removal of the tumor was performed on the 22nd postnatal day. RESULTS: Postoperatively, the right hemiparesis did not worsen and the patient did not have any new neurological deficits. The right hemiparesis gradually improved after her initial surgery, and she was able to stand by herself at 18 months of age. Adjuvant chemotherapy and radiation were administered. This patient survived for 27 months following birth, which is a relatively long time for glioblastoma cases. Radical removal at the first operation with reliance on the plasticity of infant cerebral function was the key point in the long survival.

Role of a decreased expression of the local renin-angiotensin system in the etiology of cerebral aneurysms.

BACKGROUND: Local renin-angiotensin systems (RAS) have been implicated as playing an important role in vascular remodeling. The relationship of this system to the etiology of cerebral aneurysm was investigated. METHODS AND RESULTS: The aneurysmal wall from patients with a ruptured or unruptured cerebral aneurysm and the cortical cerebral artery in control patients with head trauma or a glioma were taken during surgery for study. Local RAS were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and/or immunohistochemistry. RT-PCR analysis revealed a significantly decreased expression of angiotensin-converting enzyme (ACE), angiotensin type 1 (AT1) receptor, basic fibroblast growth factor, platelet-derived growth factor-AA, and tissue inhibitor of matrix metalloproteinases-1 mRNA in the aneurysmal wall as compared with the control cortical arterial wall. Immunohistochemistry also revealed a decreased expression of ACE, AT1 receptor, and angiotensin II in the aneurysmal wall. CONCLUSIONS: Expression of local RAS was decreased in the aneurysmal wall, which may induce aneurysm formation caused by a lack of vascular remodeling that prevents the arterial wall from thickening under increased hemodynamic stress. This is the first report that suggests that a decreased expression of local RAS plays a part in the pathogenesis of any disease.

Phenotypic modulation of smooth muscle cells and vascular remodeling in intraparenchymal small cerebral arteries after canine experimental subarachnoid hemorrhage.

Cerebral microcirculatory changes are an important factor regulating cerebral blood flow. The aim of this study was to investigate the possibility of phenotypic modulation of smooth muscle cell (SMC) and vascular remodeling of intraparenchymal small cerebral arteries after subarachnoid hemorrhage (SAH). Seven to 14 days after canine experimental SAH, in intraparenchymal perforating arteries, the amount of beta-actin mRNA evaluated by Northern blot analysis increased, the structural change of the 3' untranslated region of beta-actin mRNA detected by polymerase chain reaction analysis was enhanced, and immunohistochemistry showed marked induction of the embryonal isoform of myosine heavy chain accompanied by decreased expression of smooth muscle myosin heavy chain (SM2). Histological morphometric analysis showed an increase in the area of the arterial wall without changes in the number of nuclei of SMC. This is the first report suggesting that vascular remodeling accompanied by phenotypic modulation occurs in intraparenchymal small arteries. These changes may affect cerebral blood flow after SAH by inducing increased cerebrovascular resistance.

In vitro effects of new generation fungal derived nitric oxide donors on rabbit basilar artery.

The fungal derived nitric oxide donors, (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1-yl]-3-pyridinecarboxamide (FR144420), were evaluated for the treatment and prevention of cerebral vasospasm induced by subarachnoid hemorrhage (SAH) by an in vitro study using rabbit basilar artery. The tension-relaxation of a 3 mm-long artery segment was carried out in a micro-tissue organ bath with a real-time recorder to record the tension-relaxation curve. Steady contraction of the specimens was induced by KCI (n = 12) and oxyhemoglobin (oxyHb) (n = 12). Sodium nitroprusside was used for comparison. Each of the agents was added in ascending concentration. Relaxation caused by FK409 and FR144420 was significantly greater (p < 0.05) than that by sodium nitroprusside. Relaxation effects of FK409 and FR144420 on the KCl-induced steady contraction were better than those on the oxyHb-induced contraction. FK409 and FR144420 have potential uses for the treatment and prevention of SAH-induced cerebral vasospasm.

Effects of thrombin inhibitor on thrombin-related signal transduction and cerebral vasospasm in the rabbit subarachnoid hemorrhage model.

BACKGROUND AND PURPOSE: Thrombin is activated in the cerebrospinal fluid (CSF) after a subarachnoid hemorrhage (SAH). However, the relationship between thrombin and cerebral vasospasm has not yet been fully established. The aim of this study was to investigate the possibility of thrombin as a causative factor for cerebral vasospasm and to delineate the signal transduction mechanism that results in thrombin-inducing sustained vasoconstriction in cerebral vasospasm. METHODS: In the SAH group, SAH was simulated by the 2-hemorrhage rabbit model. In the treatment group, antithrombin III (AT-III) was injected into the cisterna magna just before production of the SAH. CSF samples were obtained serially to measure d-dimer with latex photometric immunoassay. On day 4, the basilar artery was excised after perfusion-fixation. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar arterial lumen, and the expression of mitogen-activated protein kinase (MAPK) in the vascular wall was examined with an immunohistochemical technique. RESULTS: In the treatment group, the value of d-dimer on day 4 was 0.83+/-0.07 microg/mL, which was statistically significantly lower than that in the nontreated SAH group (2.49+/-0.09 microg/mL, P<0.01). The cross-sectional area of the arterial lumen in the treatment group was 3.67x10(5)+/-1.58x10(4) square pixels, which was statistically significantly larger than that in the nontreated SAH group (2.60x10(5)+/-2.29x10(4) square pixels; P<0.01). MAPK was detected diffusely in the vascular smooth muscle cell layer in the nontreated SAH group, but it was absent in the treatment group. CONCLUSIONS: Inhibition of thrombin activity leads to amelioration of cerebral vasospasm and suppression of MAPK diphosphorylation. This suggests that thrombin and its related signal transduction, including the MAPK cascade, appear to play an important role in the pathogenesis of cerebral vasospasm after SAH.

Spontaneously ruptured craniopharyngioma cyst without meningitic symptoms --two case reports.

Two cases of spontaneous rupture of cystic craniopharyngioma without chemical meningitis are described. A 70-year-old woman complained of headache and visual field disturbance in July 1993. The tumor was extirpated in November 1993 and again in December 1996. After regular periodic follow-up evaluation, she was hospitalized for reoperation because of expansion of the cyst on magnetic resonance (MR) imaging in November 1998. However, preoperative MR imaging taken 8 weeks later revealed spontaneous reduction of the cyst. A 69-year-old woman noticed deteriorating vision and bitemporal hemianopsia in November 1998. The tumor was removed in December 1998, and 50.4 Gy postoperative radiotherapy was administered. MR imaging in May 2000 demonstrated an enlargement of the cyst, so she was hospitalized again for operation. However, preoperative MR imaging taken 7 weeks later showed spontaneous reduction of the cyst. Neither of the cases of cyst rupture were accompanied by symptoms of chemical meningitis. The signal intensity of the tumors on T1-weighted MR imaging declined after cyst reduction. Thereafter, the cysts increased in size again at 7 months and 5 months. Regular follow-up on MR imaging is necessary, since the cyst size can increase rapidly, even after spontaneous rupture.

Neuroradiologic and clinical features of arterial dissection of the anterior cerebral artery.

BACKGROUND AND PURPOSE: Case reports of nontraumatic arterial dissection of the anterior cerebral artery (ACA) have recently increased. The aim of this study was to investigate the neuroradiologic and clinical features of ACA dissection based on a series of collected cases. METHODS: The cases of 18 patients with a diagnosis of ACA dissection based on clinical signs and neuroradiologic findings from 46 stroke centers during a 5-year period were collected. The neuroradiologic and clinical records were analyzed. RESULTS: The mean patient age was 52.8 +/- 9.8 years. Five cases presented with subarachnoid hemorrhage, nine with cerebral ischemia, and four with both ischemic symptoms and subarachnoid hemorrhage. In cases presenting with ischemia, the main site of the lesion was the A2 portion and the main angiographic finding was stenosis with or without dilation. Follow-up angiography showed progression of the stenosis in the acute stage and resolution of the stenosis in the chronic stage. Hyperintensity around the flow void due to intramural hematoma on T1-weighted MR images was often seen during the second week. In all cases, the findings of MR angiography corresponded to the findings of cerebral angiography. Eight of nine cases showed a good prognosis. In three of the patients with bleeding, in whom the site of the lesion was at the A1 portion, a diffuse thick subarachnoid hemorrhage was present and surgical treatment was required but resulted in a poor prognosis. In the other patients with bleeding, in whom the site of the lesion was at the distal ACA, the prognosis was good and no rebleeding or need for surgical treatment occurred. CONCLUSION: ACA dissection presenting with ischemia has several identifiable neuroradiologic and clinical characteristics, which suggests that it may be classified as a unique clinical entity.

Effect of topically applied basic fibroblast growth factor on injured cochlear nerve.

OBJECTIVE: Trauma-induced hearing loss after cerebellopontine angle manipulation has been regarded as having a hopeless natural course once it occurs. To challenge such a pessimistic view, we investigated whether pharmacological interventions with basic fibroblast growth factor (bFGF) could ameliorate trauma-induced cochlear nerve degeneration. METHODS: The cerebellopontine angle portion of the cochlear nerve of rats was quantitatively compressed, and bFGF was topically administered for 2 weeks with a bFGF-soaked absorbable sponge and an osmotic minipump. The animals were killed 2 weeks after the compression procedure. The effect of bFGF in ameliorating cochlear neuronal death was evaluated from the residual number of spiral ganglion cells. RESULTS: Cerebellopontine angle cisternal application of bFGF ameliorated cochlear nerve degeneration after the compression. Immunocytochemical studies of FGF receptors indicated that topically administered bFGF was internalized by a receptor-mediated mechanism through FGF receptor-1 and/or FGF receptor-2. CONCLUSION: This report demonstrated that therapeutic application of bFGF was feasible to ameliorate trauma-induced cochlear nerve degeneration. Recent technological advances for deafened ears, such as cochlear implants and auditory brainstem implants, in combination with neurotrophic and/or growth factor therapeutic intervention, would be of great potential benefit for patients with hearing loss.

Pituitary abscess showing high uptake of thallium-201 on single photon emission computed tomography--case report.

A 32-year-old female presented with a rare case of pituitary abscess manifesting as homonymous hemianopsia. Serum prolactin level was slightly high (40.8 ng/ml). Magnetic resonance (MR) imaging showed the content of the lesion as homogeneously isointense on the T1-weighted images and hyperintense on the T2-weighted images. The capsule of the lesion, which appeared thin and smooth, was enhanced by gadolinium. Dural enhancement around the sella turcica was also recognized. Thallium-201 single photon emission computed tomography (201Tl SPECT) showed homogeneous high accumulation in the pituitary region on both the early and delayed images. The lesion was treated via a transnasaltranssphenoidal approach. The cystic lesion contained pus and the capsule consisted of normal pituitary gland with inflammatory changes. The patient was treated with antibiotics for 3 weeks and the pituitary abscess was cured completely. Pituitary abscess can be differentiated from pituitary adenoma as lesion with a homogeneous high uptake on 201Tl SPECT on both the early and delayed images, and no enhancement of the central portion on MR images.

Cortical blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage: three-dimensional N-isopropyl-p-[(123)I]iodoamphetamine single photon emission CT findings.

BACKGROUND AND PURPOSE: The relationship between regional cerebral blood flow (rCBF) during cerebral vasospasm after subarachnoid hemorrhage (SAH) and angiographic vasospasm and the value of rCBF in predicting vasospasm and the prognosis are not fully delineated. Our aim was to investigate the changes in extent of vasospasm-induced decreased cortical rCBF on three-dimensional (3D) displays of single photon emission CT (SPECT) findings. The clinical usefulness of these assessments was analyzed. METHODS: In 58 cases of SAH, SPECT and digital subtraction angiography were performed on the same day, 5-9 days after SAH or within 24 hours after the onset of delayed ischemic neurologic deficit (DIND). Cerebral blood flow data were assessed by measuring the area of decreased cortical rCBF on 3D SPECT images. RESULTS: The area of decreased cortical rCBF on the 3D images was significantly increased in cases with DIND (P <.001), in cases with a large infarction due to vasospasm (P =.006), and in cases with a poor prognosis after vasospasm (P =.045). These increases were also related to the type of angiographic vasospasm; the greatest decrease in cortical rCBF occurred in the combined type (combination of the peripheral and proximal types) of vasospasm, followed by cases with the peripheral type, proximal type, and no angiographic vasospasm. In cases with DIND, patchy decreased cortical rCBF areas were seen before the onset of DIND. CONCLUSION: Combined-type vasospasm leads to reductions in CBF greater than those due to isolated peripheral or proximal vasospasm. Two-dimensional and mean-hemispheric CBF analyses are less sensitive for this change than is 3D SPECT.

Risk factors for aneurysmal subarachnoid hemorrhage in Aomori, Japan.

BACKGROUND AND PURPOSE: Japan is known to have an incidence of aneurysmal subarachnoid hemorrhage (SAH) as high as that in Finland, where SAH is especially common. However, the risk factors for SAH in Japan are unknown. The purpose of this study was to identify the risk factors and then examine their possible roles in cases of SAH in Japan. METHODS: Case-control data were collected in the Aomori prefecture between June 2000 and May 2001 and in the Shimokita area between 1989 and 1998. A history of hypertension, cigarette smoking, alcohol consumption, hypercholesterolemia, and diabetes mellitus were examined as possible risk factors for SAH by using stepwise logistic regression analysis. RESULTS: Stepwise logistic regression analysis showed that a history of hypertension and current smoking increased the risk of SAH and that a history of hypercholesterolemia decreased the risk of SAH. Alcohol consumption and a history of diabetes mellitus were excluded from the model, because their log-likelihood ratios were not significant. The adjusted odds ratios, obtained by forcing matching factors, were 2.29 for a history of hypertension (95% CI, 1.66 to 3.16), 3.12 for current smoking (95% CI, 2.05 to 4.77), and 0.41 for a history of hypercholesterolemia (95% CI, 0.24 to 0.71). The prevalence of hypertension in control subjects was 27% in men and 31% in women, whereas the prevalence of cigarette smoking in control subjects was 46% in men and 9% in women. CONCLUSIONS: Hypertension and cigarette smoking seem to be independent risk factors for SAH in Japan. The high prevalence of hypertension in both sexes and the high prevalence of cigarette smoking in men in the general population might contribute to the high incidence of SAH in Japan.

Apoptosis of auditory neurons following central process injury.

Although apoptotic changes in auditory neurons induced by injury to peripheral processes (dendrites) have been intensively studied, apoptotic changes in auditory neurons induced by injury to central processes (axons of spiral ganglion cells, SGCs) have not been reported previously, probably due to lack of an experimental model. The present study reports for the first time the appearance, extent, and time course of SGC apoptosis following injury to the central processes. Apoptosis was studied in a rat model that consisted of compression of the auditory nerve in the cerebellopontine (CP) angle cistern with intraoperative recordings of auditory nerve compound action potentials (CAPs) to ensure highly reproducible results. Rats were killed between day 0 and day 14 after compression and apoptosis of SGCs was evaluated quantitatively as well as qualitatively by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, anti-activated caspase-3 immunostaining, Hoechst 33342 staining, and electron microscopy. The average number of TUNEL-positive apoptotic SGCs in each cochlear turn increased from day 1 to day 5 and then decreased gradually to an undetectable level on day 14 after compression. The average proportion of apoptotic SGCs identified in any cochlear turn on any day was always lower than 10%. The results of our present study should be useful in determining the therapeutic time window for rescuing auditory neurons undergoing apoptosis due to injury during surgery in the CP angle.

Nimodipine ameliorates trauma-induced cochlear neuronal death.

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.