PDGFR-ß Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral Stroke.

The neuroprotective agents and induction of endogenous neurogenesis remain to be the urgent issues to be established for the care of cerebral stroke. Platelet-derived growth factor receptor beta (PDGFR-ß) is mainly expressed in neural stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain; however, the role in pathological neurogenesis remains elusive. To this end, we examined the role of PDGFR-ß in the migration and proliferation of NSPCs after stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into the mice with conditional Pdgfrb-gene inactivation, including N-PRß-KO mice where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular pericytes, and E-PRß-KO mice with tamoxifen-induced systemic Pdgfrb-gene inactivation. The migration of the DCX(+) neuroblasts from the subventricular zone toward the ischemic core was highly increased in N-PRß-KO, but not in E-PRß-KO as compared to Pdgfrb-gene preserving control mice. We showed that CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in the ischemic lesion of N-PRß-KO mice. Furthermore, integrin α3 intrinsically expressed in NSPCs that critically mediates extracellular matrix-dependent migration, was upregulated in N-PRß-KO after MCAO. NSPCs isolated from N-PRß-KO rapidly migrated on the surface coated with collagen type IV or fibronectin that are abundant in vascular niche and ischemic core. PDGFR-ß was suggested to be critically involved in pathological neurogenesis through the regulation of lesion-derived chemoattractant as well as intrinsic signal of NSPCs, and we believe that a coordinated regulation of these molecular events may be able to improve neurogenesis in injured brain for further functional recovery.

Clinical significance of hemodynamic cerebral ischemia on cognitive function in carotid artery stenosis: a prospective study before and after revascularization.

BACKGROUND: Carotid stenosis is known to have negative impacts on cognitive function. However, it is still unclear through which mechanisms cognitive function is impaired in patients with carotid stenosis. This study was aimed to clarify the impact of cerebral hemodynamics on cognitive function in carotid stenosis. METHODS: This prospective study included totally 109 patients with carotid stenosis who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS). Using N-isopropyl-p-[123I]-iodoamphetamine SPECT, cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively measured in all patients before and after CEA/CAS. Based on preoperative data, the patients were categorized into three groups: Type 1 (CBF ≥32 mL/min/100 g, CVR ≥10%), Type 2 (CBF ≥32 mL/min/100 g and CVR <10%), and Type 3 (CBF <32 mL/min/100 g and CVR <10%). White matter lesions were categorized according to Wahlund grading. Cognitive function was evaluated with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and 3 months after CEA/CAS. RESULTS: Before CEA/CAS, total RBANS score was significant lower than the age-matched controls, 84±14 in Type 1 group (N.=56), 82±12 in Type 2 group (N.=43), and 70±12 in Type 3 group (N.=10). Especially, Type 3 patients had further lower score than Type 1 (P=0.008) and Type 2 (P=0.039) patients. There were no significant differences in white matter lesions among three groups. Total RBANS scores significantly improved at 3 months after CEA/CAS in all three groups, and the difference among them completely disappeared. CONCLUSIONS: These findings strongly suggest that carotid stenosis itself impairs cognitive function and compromised hemodynamic ischemia further declines it. CEA/CAS significantly improve cognitive function. The beneficial effects are most notable in patients with reduced CBF/CVR.

Neuroendoscopic biopsy and the treatment of tumor-associated hydrocephalus of the ventricular and paraventricular region in pediatric patients: a nationwide study in Japan.

A neuroendoscopic biopsy is a minimally invasive and useful procedure for the diagnosis and initial management of tumor-associated hydrocephalus. We describe the nationwide investigation of the current status of neuroendoscopic biopsy for intra- and paraventricular tumors in children, as well as the treatment of tumor-associated hydrocephalus in pediatric patients. The main items examined included the patient's age and sex, location of the tumor, pathological diagnosis, complications, treatment and efficacy of treatment of the tumor-associated hydrocephalus, and the dissemination during the postoperative course. Two hundred twenty-one pediatric patients (mean 8.6 years) from 67 institutions were registered. Endoscopic tumor biopsies were performed in 206 patients (93.2 %), and a histopathological diagnosis could be performed in 195 of these 206 patients (94.7 %). The most frequently histopathologically diagnosed tumor was a germ cell tumor (41.5 %), followed by astrocytic tumors (24.1 %) and cystic lesions (15.9 %). Associated hydrocephalus was observed in 177 patients (80.1 %), 101 of whom underwent endoscopic third ventriculostomy (ETV). The efficacy rate of the ETV in the perioperative period was 99.0 %, and the long-term response rate was 90.1 %. Perioperative complications other than fever were found in 24 patients (10.9 %). In the statistical analysis, pediatric long-term response rate to ETV (p = 0.025) showed significantly more favorable results for pediatric than adult patients (p < 0.05). Neuroendoscopic procedures involving pediatric intra- and paraventricular tumors were considered to be very useful, with a low incidence of complication, and were associated with higher safety.

[Neuroendoscopic surgery for intra- and para-ventricular tumors:impacts on biopsy and hydrocephalus treatment].

In this report, the authors retrospectively review and discuss their results for neuroendoscopic surgery for intra- and para-ventricular tumors. This study included 28 patients who were admitted to our hospital for intra- or para-ventricular tumors between January 2005 and March 2013. There were 17 males and 11 females, and their age varied widely from 1 to 75 years. Using a neuroendoscopic technique, tumor biopsy was attempted in all 28 patients. Biopsy was possible in 25 patients(89.3%)but not in the other 3(10.7%)because of hypervascularity or tumor bleeding. Of these 25 patients, pathological diagnosis was possible in 23(92%), but not in other 2(8%)because of incomplete sampling. In 18 of 28 patients, various forms of hydrocephalus were observed. Neuroendoscopic procedures were quite useful to improve cerebrospinal fluid dynamics in 13 of these patients, including endoscopic third ventriculostomy(ETV)in 9(except for 1 patient with ETV failure), septostomy with ventriculoperitoneal shunting(VPS)in 3, and cystostomy in 1. Simple VPS was performed in the other 4 patients. These results suggest that neuroendoscopic surgery is valuable as a minimally invasive procedure for pathological diagnosis and hydrocephalus treatments in patients with intra- and para-ventricular tumors. Further development of neuroendoscopic equipment is warranted to accurately diagnose tumors with hypervascularity and subependymal tumors.

Effect of carotid endarterectomy on cognitive function in patients with asymptomatic carotid artery stenosis.

BACKGROUND: This study was conducted to determine if patients with asymptomatic carotid artery stenosis show cognitive function decline, and if they experience any changes in cognitive function after carotid endarterectomy (CEA). METHOD: Cognitive function was examined in 15 patients (12 males and three females, 70.0 ± 6.5 years) with asymptomatic carotid artery stenosis before and 3 months after CEA. Cognitive function was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), two subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R 2 subtests), and the Japanese version of National Adult Reading Test (JART). The patients' average scores were compared with the normal average by one-sample t-tests, and the before and after scores were compared with paired t-tests. Changes in each patient were calculated from difference before and after CEA using 95 % confidence intervals. RESULTS: Before surgery, patients showed significant cognitive decline in RBANS total scale and immediate memory, language, and attention. At 3 months after CEA, the total scale and the immediate memory were not significantly different from the normal average. The average total scale score, the immediate memory and attention, and the WAIS-R 2 subtests scores were increased after treatment. Changes in each patient were calculated from the scores before and after CEA. At 3 months after CEA, the rate of increase in RBANS scores were 60.0 % of the patients for immediate memory, 26.7 % for visuospatial/constructional, 33.3 % for language and attention, 26.7 % for delayed memory, 47.7 % for total scale and 26.7 % for WAIS-R 2 subtests. Thus, so-called asymptomatic patients exhibit mild cognitive impairment before surgery, but after CEA, patients recover normal memory abilities. CONCLUSIONS: Our findings of mild cognitive dysfunction in asymptomatic patients suggest that they might be symptomatic after all.

Clear cell meningioma with histologically aggressive appearance and clinically aggressive behavior: a case report.

Clear cell meningioma (CCM) is an uncommon variant of meningioma, corresponding to WHO grade II. We present a case of CCM with histologically aggressive appearance and clinically aggressive behavior. The tumor demonstrated rapid regrowth and brain metastasis. The histological progression from the ordinal CCM to the atypical area and higher MIB-1 index was observed. We assume that the short time of recurrence and metastasis may result from atypical histological features in our case. If the CCM has a histologically aggressive appearance as in our case, we suggest that postoperative adjuvant radiotherapy should be performed despite total resection of the tumor.

A proposal for standardized analysis of the results of microvascular decompression for trigeminal neuralgia and hemifacial spasm.

BACKGROUND: The purpose of this study was to evaluate and analyze overall postoperative results from microvascular decompression (MVD) by combining the cure rate of symptoms with the complication rate. A new scoring system for obtaining objective surgical results from MVD for trigeminal neuralgia (TN) and hemifacial spasm (HFS) is proposed to document treatment results using consistent criteria in a standardized manner. METHOD: Surgical results combining complications , if any, were obtained from a questionnaire sent to patients who had undergone surgery for TN or HFS in recent years and had been followed-up for more than 1 year after surgery (TN patients, n = 54; HFS patients, n = 81) When surgical outcome is complete resolution of symptoms, the efficacy of surgery (E) is designated E-0, but when moderate symptoms are still persist postoperatively, the score is designated E-2. When no complications are seen after surgery, the complication score (C) is C-0, while the score is C-2 if troublesome complications remain. In addition, total evaluation of the results (T) is judged by combining the E and C scores. For example, when E is 0, and C is C-2, the total evaluation is scored as T-2, which is diagnosed as fair. FINDINGS: The response rate of the questionnaire was 80.7% (109/135). Overall surgical data were evaluated and analyzed using our new scoring system. Analysis of the collected data revealed an outcome of T-0 was 70% (35/50 patients) and T-1 was 24% (12/50) and T-2 was 6% (3/50) in TN, whereas in HFS, T-0 was 61% (36/59) and T-1 was 27.1% (16/59) and T-2 was 6.8% (4/59) and T-3 was 5.1% (3/59). CONCLUSION: The total results of MVD should be evaluated and analyzed by combining the cure rate of symptoms together with the complication rate. This new scoring system could allow much more objective analysis of the results of following MVD. Adopting this scoring system to objectively judge treatment results for TN and HFS, individual surgeons can compare their own overall surgical results with those of other institutes. Comparative results of MVD can also be provided to patients considering therapy to allow informed decision-making on the basis of good quality evidence.

Bilateral subthalamic deep brain stimulation for camptocormia associated with Parkinson's disease.

BACKGROUND: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson's disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. OBJECTIVE: We treated 4 Parkinson's disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. METHODS: The 2 female and 2 male patients in this study were 60-69 years old, with a disease duration from onset to surgery of 7-13 years and a follow-up period of 18-40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. RESULTS: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. CONCLUSIONS: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

Basic training model for supermicrosurgery: a novel practice card model.

Supermicrosurgery has been developed and reported the anastomosis of vessels with diameters of about 0.5 mm or less. The anastomosis of vessels of about 0.5 mm or less in diameter is technically more difficult than 1.0 mm or larger. This article describes a novel practice card model for acquiring basic supermicrosurgical techniques. A practice card is composed of very small-caliber silicone tubes simulating very small-caliber vessels and a thick paper. The silicone tube external diameters are 0.3, 0.5, or 0.7 mm. The thickness of the tube wall is 0.05 mm. Microsurgeons can easily begin to practice and warm up the supermicrosurgical suturing and anastomosing techniques using this nonvital practice card under a personal desk stereomicroscope in the office and an operating microscope in the operating room. This training model is a simple system for practicing basic supermicrosurgical techniques repeatedly and for warming up before a supermicrosurgical operation. This article also describes basic training regarding its use at high magnifications. This training-based supermicrosurgical skill may become a valuable technique for microsurgeons in many specialties.

[Cerebral infarction suspected due to dissection of intracranial carotid artery in 2 children].

Intracranial cerebral artery dissection in children is very rare. We report 2 children who were diagnosed as having cerebral infarction which was suspected to be due to dissection of intracranial cerebral artery. Case 1: An 11-year-old girl presented with conscious disturbance and hemiparesis after seizure. Computed tomography (CT) showed cerebral infarction in the right frontal lobe. Her symptoms did not change, but angiography demonstrated reversible change. She received conservative therapy. Case 2: A 10-year-old boy complained of headache, and presented nausea and monoparesis of the left upper extremity. CT showed cerebral infarction in the right frontal lobe. He received superficial temporal artery-middle cerebral artery anastomosis because his symptoms fluctuated. In both cases, cerebral angiography showed string sign from the supraclinoid portion of the internal carotid artery to the middle and the anterior cerebral artery. Follow-up angiography showed improvement of stenosis. In pediatric cases of cerebral artery dissection, improvement with conservative therapy is frequently reported. It is necessary to follow-up such patients closely using magnetic resonance angiography or conventional angiography to determine whether or not surgery is indicated.

Induction of autophagic cell death and radiosensitization by the pharmacological inhibition of nuclear factor-kappa B activation in human glioma cell lines.

OBJECT: The intrinsic radioresistance of certain cancer cells may be closely associated with the constitutive activation of nuclear factor-kappa B (NF-kappaB) activity, which may lead to protection from apoptosis. Recently, nonapoptotic cell death, or autophagy, has been revealed as a novel response of cancer cells to ionizing radiation. In the present study, the authors analyzed the effect of pitavastatin as a potential inhibitor of NF-kappaB activation on the radiosensitivity of A172, U87, and U251 human glioma cell lines. METHODS: The pharmacological inhibition of NF-kappaB activation was achieved using pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Growth and radiosensitivity assays were performed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining, supravital acridine orange staining, and electron microscopy were performed utilizing 3 glioma cell lines with or without pitavastatin pretreatment to identify apoptosis or autophagy after irradiation. RESULTS: The growth of these 3 glioma cell lines was not significantly inhibited by pitavastatin at a concentration of up to 1 microM. Treatment with 0.1 microM of pitavastatin enhanced radiation-induced cell death in all glioma cell lines, with different sensitivity. Apoptosis did not occur in any pretreated or untreated (no pitavastatin) cell line following irradiation. Instead, autophagic cell changes were observed regardless of the radiosensitivity of the cell line. An inhibitor of autophagy, 3-methyladenine suppressed the cytotoxic effect of irradiation with pitavastatin, indicating that autophagy is a result of an antitumor mechanism. Using the most radiosensitive A172 cell line, the intracellular localization of p50, a representative subunit of NF-kappaB, was evaluated through immunoblotting and immunofluorescence studies. The NF-kappaB of A172 cells was immediately activated and translocated from the cytosol to the nucleus in response to irradiation. Pitavastatin inhibited this activation and translocation of NF-kappaB. CONCLUSIONS: Autophagic cell death rather than apoptosis is a possible mechanism of radiation-induced and pitavastatin-enhanced cell damage, and radiosensitization by the pharmacological inhibition of NF-kappaB activation may be a novel therapeutic strategy for malignant gliomas.

Brain cortical mapping by simultaneous recording of functional near infrared spectroscopy and electroencephalograms from the whole brain during right median nerve stimulation.

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5-15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.

Malignant transformation of supratentorial clear cell ependymoma.

Recurrence of clear cell ependymoma is not a rare condition, but malignant transformation of clear cell ependymoma has not yet been well presented. The authors report a 44-year-old man who presented with progressive right hemiparesis. A brain tumor in the left frontal premotor area was removed and an initial pathological diagnosis of oligodendroglioma was made. The tumor recurred 4 months later, and reoperation of the tumor and adjuvant local radiotherapy were performed. The patient subsequently underwent surgical removal of recurrent tumors on another four occasions (6 times in total) during a period of 11 years and finally died of the original disease. Histopathological studies of all surgical and autopsy specimens were carried out. The first and second surgical specimens did not contain any ependymal rosettes or pseudorosettes, and thus a diagnosis of oligodendroglioma was made. However, the third surgical specimen showed pseudorosettes. At this time, the tumor had an ultrastructural appearance compatible with ependymoma. Thereafter, the recurrent tumors showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopallisading. The autopsy specimens resembled a feature of glioblastoma but the tumor was sharply demarcated from the surrounding parenchyma.

Folliculostellate cell tumor in pituitary gland.

A 33-year-old woman presented with visual field defects. Magnetic resonance imaging demonstrated a pituitary tumor with suprasellar extension. The tumor was partially removed by trans-sphenoidal surgery. Histologically, the tumor was composed of fascicles of spindle cells which were immunohistochemically positive for S-100 protein, Galectin-3, vimentin and EMA. Based on the morphology and immunostaining pattern, diagnosis of folliculostellate cell tumor in the pituitary gland was given.

Changes in cognitive function during the 1-year period following endarterectomy and stenting of patients with high-grade carotid artery stenosis.

BACKGROUND: In patients with severe carotid artery stenosis, cognitive decline and changes in cognitive function before to after treatment have been noted, though the true effects of treatment in such patients remain unclear. A convenient and repeatable neuropsychological test battery is needed for such patients. METHODS: In 26 patients with severe carotid artery stenosis treated by carotid endarterectomy (CEA) and stenting (CAS), cognitive function was examined before and 1 week, 3 months, 6 months, and 1 year after treatment. RBANS and MMSE were selected as a test battery, and changes in test scores and long-term results of revascularization were evaluated. RESULTS: RBANS was useful and suitable for neuropsychological testing in such patients, and yielded the following results: (1) Patients before treatment had, on average, RBANS scores rated low average, with mild but relatively diffuse cognitive impairment; (2) RBANS scores were increased significantly at 3 months after CEA and CAS, and cognitive improvement was maintained over 1 year; and (3) scores were decreased temporarily at 1 week after CEA, but not after CAS. CONCLUSIONS: Patients with severe carotid artery stenosis exhibited mild decline in cognitive function, which was improved after CEA and CAS. RBANS is a suitable test battery for this type of patient.

A development of atheromatous plaque is restricted by characteristic arterial wall structure at the carotid bifurcation.

BACKGROUND: It is said atheromatous plaque is located very focally, but there have been few reports regarding this matter. Various aspects of the pathogenesis of the development of atheromatous plaque at the carotid bifurcation have previously been discussed. We have noted the correlation of plaque localization with characteristics of the cervical carotid artery wall. METHODS: Morphological and histopathologic changes in the carotid bifurcation were examined in 72 cadaver cases with or without atheromatous plaque. We determined the level at which the wall structure changed to muscular artery from elastic artery and analyzed its influence on the development of atheromatous plaque. RESULT: Atheromatous plaques at the distal site of the ICA extended within 0 to 37 mm from the carotid bifurcation. The proximal side of the CCA more than 5 mm away from the bifurcation was elastic artery, whereas the distal side of the ICA more than 15 mm from the bifurcation was muscular artery. The area of the carotid bifurcation between elastic artery and muscular artery was a transitional zone. Approximately 80% of them were located within 15 mm, and these areas were coincident with the transitional zone. CONCLUSION: Most atheromatous plaque was located in the transitional zone. The arterial wall structure is related to the development of atheromatous plaque at the cervical carotid bifurcation.

A new training method to improve deep microsurgical skills using a mannequin head.

Neurosurgeons need fine and special microsurgical techniques, such as the ability to suture deep microvasculature. Intensive training is required to perform microsurgery, especially in deep microvascular anastomosis. There have been many previous reports of training methods for typical microsurgical techniques, including suturing of surgical gloves, Silastic tubes, living animals, and chicken wing arteries. However, there have been no reports of training methods to improve deep microsurgical skills under the various hand positions specific to neurosurgical operation. Here, we report a new training method using a mannequin head, water balloons, and clay to mimic actual deep microsurgery in the brain. This method allows trainees to experience microsurgery under various hand positions to approach the affected areas located at various depths in the brain from various angles.

Involvement of meteorological factors and sex in the occurrence of subarachnoid hemorrhage in Japan.

The sex difference in the seasonal occurrence of subarachnoid hemorrhage (SAH) and the association of meteorological factors in Japan were analyzed in 1006 consecutive patients with SAH in Toyama, Japan from 1996 to 2000. The study investigated whether these meteorological factors could explain the seasonality of the incidence of SAH in each sex. Seasonal variation of SAH occurrence peaked in spring in men, but peaked in spring and winter in women. The difference between maximum temperature and minimum temperature was the greatest on the day previous to SAH occurrence in multiple individuals in men, whereas mean humidity was the greatest on that day in women. Interestingly, the difference between maximum temperature and minimum temperature peaked in spring and mean humidity in winter from the meteorological data over the 5 years. The relationship between humidity and occurrence of SAH may explain the sex difference of the incidence of aneurysmal SAH. The humidity change may be a specific and additional meteorological factor for the incidence of SAH in women.

Enzymatic and biochemical properties of a novel human serine dehydratase isoform.

A cDNA clone similar to human serine dehydratase (SDH) is deposited in the GenBank/EMBL databases, but its structural and functional bases remain unknown. Despite the occurrence of mRNA, the expected protein level was found to be low in cultured cells. To learn about physicochemical properties of the protein, we expressed the cDNA in Escherichia coli, and compared the expressed protein with that of a hepatic SDH. The purified protein showed l-serine and l-threonine dehydratase activity, demonstrating to be an isoform of SDH. However, their Km and Vmax constants were different in a range of two-order. Removal of Pro128 from the hepatic SDH consisting of 328 residues, which is missing in the corresponding position of the isoform consisting of 329 residues, significantly changed the Michaelis constants and Kd value for pyridoxal 5'-phosphate, whereas addition of a proline residue to the isoform was without effect. These findings suggest the difference in the structures of the active sites of the two enzymes. Another striking feature was that the expressed level of the isoform in E. coli was 7-fold lower than that of the hepatic SDH. Substitution of Val for Leu287 in the isoform dramatically increased the protein level. The high yield of the mutated isoform was also confirmed by the in vitro transcription and translation experiment. The poor expression of the isoform could be explained by the more stable secondary structure of the mRNA than that of the hepatic SDH mRNA. The present findings may provide a clue as to why the protein level in cultured cells is low.

Neuroprotective role of transgenic PAF-acetylhydrolase II in mouse models of focal cerebral ischemia.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. METHODS: Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. RESULTS: Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P<0.05) lower in transgenic mice (1.30+/-0.72, 1.12+/-0.04, and 14.0+/-7.7%, respectively) than in wild-type mice (2.56+/-0.93, 1.23+/-0.12, and 31.9+/-9.7%, respectively). Percentages of apoptotic cells were also significantly (P<0.001) lower in transgenic mice (cortex, 5.2+/-3.3%; hippocampus, 3.4+/-7.0%) than in wild-type mice (cortex, 41.1+/-16.9%; hippocampus, 58.9+/-15.3%). CONCLUSIONS: These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.