bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain
Authors: Prunell Giselle F. , Svendgaard Niels-Aage , Alkass Kanar , Mathiesen Tiit 
Published: May 2009

Object. The authors tested the hypotheses that subarachnoid hemorrhage (SAH) leads to delayed cell death with the participation of apoptotic-like mechanisms and is influenced by the degree of acute decrease in the cerebral blood flow (CBF) following hemorrhage.
Methods. Subarachnoid hemorrhage was induced in rats by endovascular perforation of the internal carotid artery or injection of blood into the prechiasmatic cistern. Cerebral blood flow was measured using laser Doppler flowmetry for 60 minutes. Brain sections stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) showed DNA fragmentation at 2 and 7 days after both methods of inducing SAH in one third to two thirds of the surviving animals in the different experimental groups. More than 80% of the TUNEL-positive cells were neuron-specific nuclear protein—positive (neurons), but immunoreactivity to glial fibrillary acidic protein (astrocytes) and transferrin (oligodendrocytes) were markedly decreased in TUNEL-positive areas. Most of the TUNEL-positive cells displayed chromatin condensation and/or blebs and immunostained for increased Bax; approximately 50% of them were immunoreactive to cleaved caspase-3 and a few to Bcl-2. The duration of the acute CBF decrease below 30% of the baseline level was related to the degree of TUNEL staining.
Conclusions. Subarachnoid hemorrhage resulted in delayed cell death in a large proportion, but not all, of the surviving animals. The acute CBF decrease was related to the degree of subsequent cell death. These findings indicated the relevance of apoptotic-like pathways. There appears to be a temporal therapeutic window during which adequate treatment might reduce the final damage following SAH.
Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats
Authors: Lee E-Jian , Lee Ming-Yang , Chang Guan-Liang , Chen Li-Hsuan , Hu Yu-Ling , Chen Tsung-Ying , Wu Tian-Shung 
Published: May 2009

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion.
Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died.
Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively.
Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.
Acute microvascular platelet aggregation after subarachnoid hemorrhage
Authors: Sehba Fatima A. , Mostafa Gulam , Friedrich Victor , Bederson Joshua B. 
Published: May 2009

Object. The mechanisms underlying acute cerebral ischemia after subarachnoid hemorrhage (SAH) are not well established. Platelets aggregate within major cerebral vessels hours after SAH, but this has not been studied in the microvasculature. Platelet aggregates within the microvasculature could mechanically obstruct the lumen and initiate events that injure vessel structure. In the present study the authors examined the hypothesis that platelets aggregate within the cerebral microvasculature acutely after SAH.
Methods. Subarachnoid hemorrhage was induced in the rat by using the endovascular perforation model. The animals were killed between 10 minutes and 48 hours after SAH. Immunostaining for the platelet surface receptor glycoprotein (GP)IIb/IIIa, which mediates platelet aggregation, was used to detect platelet aggregation. Sham-operated animals were used as controls.
The GPIIb/IIIa immunoreactive platelet aggregates were abundant in the microvasculature of the basal and frontal cortex, striatum, and hippocampus 10 minutes after SAH. These aggregates decreased in number from 1 to 6 hours post-SAH and then increased to a peak at 24 hours. No immunoreactive aggregates were observed 48 hours after SAH.
Conclusions. The data indicate that widespread platelet aggregation occurs very rapidly in response to SAH followed by a decrease within 6 hours and a subsequent increase 24 hours after SAH. Microvascular platelet aggregates may contribute to decreased cerebral blood flow and ischemic injury after SAH via a number of mechanisms.
Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction
Authors: Vatter Hartmut , Zimmermann Michael , Tesanovic Veronika , Raabe Andreas , Schilling Lothar , Seifert Volker 
Published: May 2009

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature.
Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2).
The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−).
Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.
Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist shown to be clinically effective for the treatment of cerebral vasospasm. Part II: Effect on endothelinB receptor—mediated relaxation
Authors: Vatter Hartmut , Zimmermann Michael , Tesanovic Veronika , Raabe Andreas , Seifert Volker , Schilling Lothar 
Published: May 2009

Object. The disturbed balance between nitric oxide and endothelin (ET)—1 in the cerebrovasculature seems to play a major role in the development of cerebral vasospasm after subarachnoid hemorrhage. Endothelin-1 represents the contractile part in this balance. In addition to the prevailing ETA receptor—dependent contractile effect, ET-1 also has ETB receptor—mediated vasodilatory attributes. The aim of the present study was to define the actual selectivity of clazosentan, the first putative highly ETA receptor—selective antagonist clinically proven to be effective in the treatment of vasospasm in the cerebrovasculature.
Methods. Rat basilar artery ring segments with endothelial function were used for the measurement of isometric force. Concentration effect curves were constructed by cumulative application of sarafotoxin S6c, ET-1, or big ET-1 in the presence or absence of clazosentan (10−9 to 10−6 M) after a precontraction was induced by prostaglandin F2α. The inhibition by clazosentan was estimated by the value of the affinity constant (pA2).
The relaxation induced by sarafotoxin S6c, ET-1, and big ET-1 was inhibited in a competitive manner by clazosentan, yielding pA2 values of 7.1, 6.7, and 6.5, respectively. The selectivity to the ETA receptor in the cerebrovascular system was approximately two logarithmic units.
Conclusions. The present investigation shows a competitive inhibition of ETB receptor—mediated relaxation in cerebral vessels by clazosentan in therapeutically relevant concentrations. Thus, additional clinical trials should be undertaken to evaluate clazosentan concentrations in cerebrospinal fluid. Furthermore, the present data may be taken to describe the pharmacological properties for an ET receptor antagonist specifically tailored for the treatment of pathological conditions of impaired cerebral blood flow.
Suppression of secondary generalization of limbic seizures by stimulation of subthalamic nucleus in rats
Authors: Usui Naotaka , Maesawa Satoshi , Kajita Yasukazu , Endo Otone , Takebayashi Shigenori , Yoshida Jun 
Published: May 2009

Object. Deep brain stimulation (DBS) of subcortical nuclei such as the subthalamic nucleus (STN) or the substantia nigra pars reticulata (SNR) may provide an alternative therapy for intractable epilepsy. The authors attempted to evaluate the antiepileptic effects of DBS to these structures in an experimental seizure model.
Methods. Three groups of rats were prepared. In the first two groups, the rats underwent unilateral implantation of stimulation electrodes in the STN (six rats) or the SNR (six rats). A control group received no electrodes (six rats). Kainic acid (KA) was systemically administered to induce limbic seizures, which started with focal seizures and became generalized secondarily. High-frequency electrical stimulation of the STN or SNR was begun immediately after KA administration, and changes on electroencephalography (EEG) and the magnitude of clinical seizures were evaluated. Results showed that STN stimulation significantly reduced the duration of generalized seizures on EEG, although the total duration of seizures (generalized plus focal seizures) was unchanged. The duration of focal seizures on EEG was prolonged by STN DBS, a result possibly due to the suppression of secondary generalization. In addition, STN DBS reduced the severity of clinical seizures. On the other hand, stimulation of the SNR demonstrated no effect.
Conclusions. Unilateral STN DBS showed significant suppression of the secondary generalization of limbic seizures. Note, however, that SNR DBS was less effective, which implies that in addition to the nigral control of the epilepsy system, another antiepileptic mechanism such as antidromic stimulation of the corticosubthalamic pathway should be considered.
Prolonged intrathecal baclofen withdrawal syndrome
Authors: Douglas Andrea F. , Weiner Howard L. , Schwartz David R. 
Published: May 2009

✓ The authors describe a patient who experienced a prolonged course of intrathecal baclofen withdrawal syndrome after removal of an implantable baclofen pump for treatment of pump infection and meningitis. The current literature outlines management options for the acute management of this syndrome. In this report the authors discuss the long-term presentation of this syndrome and suggest a treatment strategy for management of the syndrome.
A 37-year-old man who presented with a baclofen pump infection and meningitis experienced acute onset of intrathecal baclofen withdrawal syndrome 12 hours after the pump had been surgically removed. The patient's symptoms evolved into a severe, treatment-refractory withdrawal syndrome lasting longer than 1 month.
Oral baclofen replacement with adjunctive administration of parenteral γ-aminobutyric acid agonists only served to stabilize the patient's critical condition throughout his hospital course. Replacement of the baclofen pump and restoration of intrathecal delivery of the medication was necessary to trigger the patient's dramatic recovery and complete reversal of the withdrawal syndrome within approximately 48 hours.
These findings indicate that a more direct method of treating infected baclofen pumps than immediate surgical removal is necessary to prevent the onset of intrathecal baclofen withdrawal syndrome. Various options for preventing the onset of the syndrome while simultaneously treating the infection are discussed.
Resolution of neurogenic arterial hypertension after suboccipital decompression for Chiari malformation
Authors: Naderi Sait , Acar Feridun , Acar Göksemin , Men Süleyman 
Published: May 2009

✓ A Chiari malformation Type I may remain asymptomatic until the patient has reached adulthood and acute presentation of symptoms occurs. In several clinical and experimental studies it has been shown that essential hypertension is associated with vascular compression of the brainstem, particularly of the rostral ventrolateral medulla oblongata. Nevertheless, two cases of Chiari malformation and neurogenic arterial hypertension have been reported. In this article the authors describe a patient with Chiari malformation Type I and neurogenic arterial hypertension. A simple suboccipital decompression not only provided neurological improvement, but also led to resolution of the hypertension.
In cases of Chiari malformation and concomitant neurogenic arterial hypertension careful preoperative clinical and neuroimaging assessments may reveal the cause of the arterial hypertension. Resolution of neurogenic arterial hypertension may be expected even in a case of simple suboccipital decompression.
Computational model for the estimation of the extracranial doses received during Leksell gamma knife model C treatment
Authors: Majali Mustafa , Novotny Josef , Novotny Josef 
Published: May 2009

Object. Extracranial doses received by patients undergoing Leksell gamma knife surgery (GKS) can be of clinical concern. Therefore, the ability to preestimate peripheral doses received outside the treatment field during the GKS would be beneficial and could be used for the optimization of treatment planning by providing a reference for practitioners to calculate the extracranial dose burden to the body before the start of treatment.
Methods. A dose of 40 Gy was delivered to the Rando phantom in a single fraction to a midline hypothetical target close to the center of the skull. Treatment planning was performed for multiple isocenters with a prescription to the 50% isodose of each collimator. Treatment plans were produced for 1, 5, 10, 15, and 20 shots, keeping the same dose and dose distribution at different target volumes. An automatic positioning system was used for positioning the phantom during the treatment. The doses to different organs were measured during GKS using a thermoluminescent dosimeter. In vivo measurements were also made in 200 patients who underwent GKS with the model C unit for different diagnoses at Na Homolce Hospital.
Conclusions. The peripheral dose depended on the collimator size with a logarithmic dependence on collimator size and a linear dependence on the number of shots. This model can be used for the estimation of peripheral doses with a total error less than 20%. This information can help clinicians with treatment planning optimization, especially in patients with long survival expectancy.
Low-grade gliomas treated by fractionated gamma knife surgery
Authors: Simonová Gabriela , Novotny Josef , Liscák Roman 
Published: May 2009

Object. The authors sought to evaluate local tumor control, complications, and progression-free survival in patients harboring low-grade gliomas who were treated with Leksell gamma knife surgery (GKS).
Methods. During a 6-year period 70 patients were treated for verified low-grade gliomas (Grade I or II) by GKS. Statistical analysis was based on 68 patients; two patients were lost to follow up. The median patient age was 17 years. The median target volume was 4200 mm.3 The median prescription dose was 25 Gy. The median number of fractions was five. Ninety-five percent of patients were treated in five daily fractions.
Partial or complete tumor regression was achieved in 83% of patients with a median time to response of 18 months. There was moderate acute or late toxicity in not more than 5% of patients. In this series the progression-free survival was 92% at 3 years and 88% at 5 years.
Conclusions. Relatively high local tumor control with minimal complications was achieved.
A comparison of the gamma knife model C and the Automatic Positioning System with Leksell model B
Authors: Tlachacova Daniela , Schmitt Michal , Novotny Josef , Novotny Josef , Majali Mustafa , Liscak Roman 
Published: May 2009

Object.The authors sought to compare the quality of treatment planning, radiation protection, and the time taken for treatment in the Leksell gamma knife model B with that using the model C Automatic Positioning System (APS).Methods.Data were obtained in 463 patients treated with the B model and 518 patients treated with the C model. Data were analyzed in patients in whom the following diagnoses had been made: vestibular schwannoma, pituitary adenoma, meningioma, solitary metastasis, and other benign and malignant solitary tumors. Patients with arteriovenous malformations, ocular lesions, and functional diagnoses were excluded from this study.Conclusions.With the C model there was a better conformity for most treated targets, such as vestibular schwannomas (p = 0.005) and meningiomas (p = 0.015). The level of radiation exposures to personnel was significantly decreased when using the model C (p < 0.001). There was no significant difference in radiation exposure of extracranial structures for the same number of shots in patients treated by both models. The mean time saved using the C model with the APS was 41 minutes per treatment. It would seem that the gamma knife model C permits better dose conformity, shorter treatment times, and less radiation exposure to personnel.
Treatment of essential trigeminal neuralgia with gamma knife surgery
Authors: Urgosik Dusan , Liscak Roman , Novotny Josef , Vymazal Josef , Vladyka Vilibald 
Published: May 2009

Object.The authors present the long-term follow-up results (minimum 5 years) of patients with essential trigeminal neuralgia (TN) who were treated with gamma knife surgery (GKS).Methods.One hundred seven patients (61 females and 46 males) underwent GKS. The median follow up was time was 60 months (range 12–96 months). The target was the trigeminal root, and the maximum dose was 70 to 80 Gy. Repeated GKS was performed in 19 patients for recurrent pain, and the same dose was used.Initial successful results were achieved in 96% of patients, with complete pain relief in 80.4%. Relief was achieved after a median latency of 3 months (range 1 day–13 months). Gamma knife surgery failed in 4% of patients. Pain recurred in 25% of patients after a median latent interval of 36 months (6–94 months). The initial success rate after a second GKS was 89% and 58% of patients were pain free. Pain relapse occurred in only one patient in this group. Hypesthesia was observed in 20% of patients after the first GKS and in 32% after the second GKS. The median interval to hypaesthesia was 35 months (range 3–94 months) after one treatment and 21 months (range 1–72 months) after a second treatment.Conclusions.The initial success rate of pain relief was high and comparable to that reported in other studies. A higher than usual incidence of sensory impairment after GKS could be the long duration of follow-up study and due to the detailed neurological examination.
The effect of gamma knife irradiation on functions of striatum in rats
Authors: Tokumaru Osamu , Tomida Mihoko , Katayama Yoko , Hayashi Mootohiro , Kawakami Yoriko , Kouyama Nobuo 
Published: May 2009

Object.An animal model has been developed to study the effect of gamma knife surgery(GKS) on cerebral function.Methods.A rat was fixed in a newly developed Régis—Valliccioni frame that enables the target region to be planned directly on the magnetic resonance images. The left striatum was irradiated with 150 Gy via a 4-mm collimator of the Leksell gamma knife. Apomorphine (dopamine agonist) was administered to elicit a circling behavior (apomorphine test) after the GKS so as to examine the time course of the changes in dopaminergic functions of irradiated striatum. After a series of behavioral analyses, irradiated brains were subjected to histological examination.Necrosis was observed in the irradiated area surrounded by hemorrhage and gliosis. The distance between the histologically estimated and planned centers of the irradiation areas was 1.0 ± 0.5 mm. The extent of the distance was due to errors along dorsoventral axis. The distribution of the irradiation areas influenced the activity and the circling behaviors in apomorphine test, which was suggestive of involvement of the nigrostriatal pathway.Conclusions.Targeting by using the Régis—Valliccioni frame was very accurate compared with targeting with coordinates based on brain maps used hitherto. Although targeting improved the accuracy, further effort will still be necessary to reduce errors along dorsoventral axis. The apomorphine test indicated a reduced dopaminergic function of the irradiated area including striatum, which accompanied histological changes after a high dose of irradiation (150 Gy).