bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotection by the stable nitroxide 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia
Authors: Hu Guohan , Lyeth Bruce G. , Zhao Xueren , Mitchell James B. , Watson Joe C. 
Published: May 2009

Object. Nitroxides mimic superoxide dismutase (SOD) biochemically and may prevent free radical oxidative injury in settings in which endogenous SOD is overwhelmed. The authors have previously shown the efficacy of a nitroxide, Tempol, in reducing stroke infarct size. Of the nitroxides, 3-carbamoyl-proxyl (3-CP) is especially promising for clinical use, because it does not cause hypotension in animals. Its efficacy in brain ischemia, however, is untested. The goal of this study was to ascertain whether 3-CP would reduce brain damage in a rat ischemia—reperfusion model.
Methods. The authors performed a blinded, dose—response study of the effect of different amounts of 3-CP (1, 10, and 100 mg/kg) on infarct size at 24 hours after focal ischemia and reperfusion. The 3-CP was given intravenously during reperfusion, which followed 1 hour of reversible ischemia induced by a thread placed intraluminally in the middle cerebral artery of rats. Brain infarcts, measured with 2,3,5-triphenyltetrazolium chloride staining in six 3-CP groups, were compared with those measured in controls (animals given an equal volume of saline).
Edema-corrected infarct sizes (mean ± standard deviation) were as follows: 146 ± 64 mm3 in controls; 107 ± 18 mm3 in rats given 1 mg/kg 3-CP; 40 ± 20 mm3 in those given 10 mg/kg 3-CP; and 44 ± 17 mm3 in those given 100 mg/kg 3-CP. A statistically significant reduction in infarct size was achieved in the 10- and 100-mg/kg 3-CP—treated groups (p < 0.01). A reduction in infarct size was also seen in the 1 mg/kg 3-CP—treated group, but this did not reach statistical significance. The authors observed no effects of 3-CP on blood pressure or brain temperature.
Conclusions. Given at reperfusion, 3-CP significantly decreases brain infarct size at doses of 10 and 100 mg/kg without causing hypotension. The authors found that 3-CP is well suited for further laboratory and clinical use in brain ischemia and reperfusion.
Reduced brain infarct volume and improved neurological outcome by inhibition of the NR2B subunit of NMDA receptors by using CP101, 606-27 alone and in combination with rt-PA in a thromboembolic stroke model in rats
Authors: Yang Yi , Li Qiu , Yang Tao , Hussain Munawar , Shuaib Ashfaq 
Published: May 2009

Object. A novel postsynaptic antagonist of N-methyl-d-aspartate (NMDA) receptors, CP-101,606-27 may attenuate the effects of focal ischemia. In current experiments, the authors investigated its neuroprotective effect alone and in combination with recombinant tissue plasminogen activator (rt-PA) in thromboembolic focal cerebral ischemia in rats.
Methods. Forty-eight male Wistar rats underwent embolization of the right middle cerebral artery to produce focal cerebral ischemia. After random division into six groups (eight rats in each group), animals received: vehicle; low-dose (LD) CP-101,606-27, 14.4 mg/kg; high-dose (HD) CP-101,606-27, 28.8 mg/kg; rt-PA, 10 mg/kg; low-dose combination (LDC) CP-101,606-27, 14.4 mg/kg plus rt-PA, 10 mg/kg; or high-dose combination (HDC) CP-101,606-27, 28.8 mg/kg plus rt-PA, 10 mg/kg) 2 hours after induction of embolic stroke. Animals were killed 48 hours after the onset of focal ischemia. Brain infarction volume, neurobehavioral outcome, poststroke seizure activity, poststroke mortality, and intracranial hemorrhage incidence were observed and evaluated. Compared with vehicle-treated animals (39.4 ± 8.6%) 2 hours posttreatment with CP-101,606-27 or rt-PA or in combination a significant reduction in the percentage of brain infarct volume was seen (LD CP-101,606-27: 20.8 ± 14.3%, p < 0.05; HD CP-101,606-27: 10.9 ± 3.2%, p < 0.001; rt-PA: 21.1 ± 7.3%, p < 0.05; LDC, 18.6 ± 11.5%, p < 0.05; and HDC: 15.2 ± 10.1%, p < 0.05; compared with control: 39.4 ± 8.6%). Combination of CP-101,606-27 with rt-PA did not show a significantly enhanced neuroprotective effect. Except for the control and LDC treatment groups, neurobehavioral outcome was significantly improved 24 hours after embolic stroke in animals in all other active therapeutic groups receiving CP-101,606-27 or rt-PA or in combination. The authors also observed that treatment with HD CP-101,606-27 decreased poststroke seizure activity.
Conclusions. The data in this study suggested that postischemia treatment with CP-101,606-27 is neuroprotective in the current stroke model; however, the authors also note that although rt-PA may offer modest protection when used alone, combination with CP-101,606-27 did not appear to enhance its effects.
Improvement in brainstem auditory evoked potentials after suboccipital decompression in patients with Chiari I malformations
Authors: Anderson Richard C. E. , Emerson Ronald G. , Dowling Kathryn C. , Feldstein Neil A. 
Published: May 2009

Object. The optimal treatment for patients with symptoms related to Chiari I malformation remains controversial. Although a suboccipital decompression with duraplasty is most commonly performed, there may be a subset of patients who improve in response to bone decompression alone. In an initial attempt to identify such patients, we performed a continuous study of intraoperative brainstem auditory evoked potentials (BAEPs) in patients undergoing a standard decompression with duraplasty and compared conduction times at three different time points: 1) baseline while the patient is supine (before positioning); 2) immediately after opening of the bone and release of the atlantooccipital membrane (that is, the dural band); and 3) after opening of the dura mater.
Methods. Eleven children and young adults (mean age 9.8 years) with symptoms related to Chiari I malformation underwent suboccipital decompression and duraplasty with intraoperative monitoring of BAEPs and somatosensory evoked potentials (SSEPs). Six patients (55%) had associated syringomyelia.
At baseline, the I to V interpeak latency (IPL) for both sides (total 21 BAEPs) was 4.19 ± 0.22 msec (mean ± standard deviation). After complete bone decompression and before the dura mater was opened, the I to V IPL decreased to 4.03 ± 0.25 msec (p = 0.0005). When the dura was opened, however, no further decrease in the I to V IPL was detected (4.03 ± 0.25 msec; p = 0.6). The SSEPs remained stable throughout the procedure.
Conclusions. In children and young adults undergoing suboccipital decompression with duraplasty for Chiari I malformation, the vast majority of improvement in conduction through the brainstem occurs after bone decompression and division of the atlantooccipital membrane, rather than after opening of the dura. Additional studies are needed to establish whether the improvement seen with BAEP monitoring during bone decompression will predict long-term clinical improvement in these patients.
Localization of language function in children: results of electrical stimulation mapping
Authors: Ojemann Steven G. , Berger Mitchel S. , Lettich Ettore , Ojemann George A. 
Published: May 2009

Object. The authors examined the localization of language sites and the frequency of naming errors at these sites in a population of children undergoing electrical stimulation mapping during surgeries in which epileptic foci and dominant hemisphere neoplasms were resected. The frequency with which essential language sites were found (that is, “the frequency of language sites”) in children was compared with that of a population of adults who had undergone this procedure, to assess the relationship of age to the distribution of essential areas for language.
Methods. The results of electrical stimulation mapping to determine sites of naming and speech arrest in 26 children ranging in ages from 4 to 16 years are presented in this report. Mapping was performed in the intraoperative setting in eight patients and in the extraoperative setting, by stimulation across a subdural grid, in 18 patients. The frequency and distribution of essential language areas were analyzed in populations of different ages and according to the method used to obtain the map.
Considerable variability was found in the localization of language sites. When the language site distribution in pediatric patients was compared with the language site distribution found previously in a population of patients older than 16 years of age, a relative paucity of language sites was found in all perisylvian cortices in the younger age group. This relationship was also found within the group of patients 16 years of age and younger, when segregated into two groups: those patients 8 years of age or younger, and those patients between 9 and 16 years of age. These findings are relevant to theories of the intrahemispheric organization of the cortex devoted to language function.
Conclusions. The differences found between groups of younger and older patients in the frequencies of sites where stimulation produces naming errors was identified suggests the possibility that, with advancing age, maturational processes contribute new foci of cortex essential for language.
Clinical experience with the use of a shunt with an adjustable valve in children with hydrocephalus
Authors: Zemack Göran , Bellner Johan , Siesjö Peter , Strömblad Lars-Göran , Romner Bertil 
Published: May 2009

Object. The goal of this study was to assess the value of making adjustments in the opening pressure of a shunt valve and to determine shunt survival in children and young adults in whom an adjustable valve was used to manage cerebrospinal fluid drainage.
Methods. The authors conducted a single-center retrospective study of 158 children and young adults who had received 199 Codman Hakim programmable valves (noninvasively adjustable to settings in the range of 30–200 mm H2O). The mean age at which the patients underwent shunt implantation was 4.4 years (median 0.4 years, maximum 18 years); 94 patients were younger than 2 years of age, including 14 patients with a gestational age younger than 38 weeks at the time of implantation. In 84 (53.2%) of the 158 patients, valve pressure adjustment was required at least once (mean 1.3 times, maximum 16 times). Among the 202 adjustments made in patients the reason for adjustment was underdrainage in 74 adjustments (36.6%) and overdrainage in 119 (58.9%). The clinical status of the patient improved after 121 (69.1%) of 175 adjustments and after 58 (73.4%) of 79 minor adjustments (less than or equal to ± 20 mm H2O). The shunt infection rate was 13 (10.9%) of 119 patients. Shunt survival was 60.5% at 1 year, 47.1% at 2 years, and 43.9% at 3 years of follow-up review.
Conclusions. Adjustment of the valve's opening pressure further improves outcome in pediatric patients.
Endovascular therapy for stenosis of the petrous or cavernous portion of the internal carotid artery: percutaneous transluminal angioplasty compared with stent placement
Authors: Terada Tomoaki , Tsuura Mitsuharu , Matsumoto Hiroyuki , Masuo Osamu , Tsumoto Tomoyuki , Yamaga Hiroo , Itakura Toru 
Published: May 2009

Object. The effects of percutaneous transluminal angioplasty (PTA) and stent placement for stenosis of the petrous or cavernous portion of the internal carotid artery (ICA) were compared.
Methods. Twenty-four patients with symptomatic, greater than 60% stenosis of the petrous or cavernous portion of the ICA were treated using PTA or stent placement; 15 were treated with PTA and nine with stent insertion. Initial and follow-up results (> 3 months posttreatment) were compared in each group.
Stenotic portions of the ICA were successfully opened in 13 of 15 patients in the PTA group, and in all nine patients in the stent-treated group. In one case in the PTA group stent delivery was attempted; however, the device could not pass through the vessel's tortuous curve, and PTA alone was performed in this case. Postoperatively, the mean stenotic ratio decreased from 72.1 to 29.6% in the PTA group, and from 75.6 to 2.2% in the stent-treated group. In four patients in the PTA group, stenoses greater than 50% were demonstrated on follow-up angiography performed at 3 to 6 months after PTA. In the stent-treated group, no restenosis was encountered, although in one case acute occlusion of the stent occurred; the device was recanalized with PTA and infusion of tissue plasminogen activator. This case was the only one of the 24 in which any neurological deficits related to the endovascular procedure occurred. Stent placement brought a greater gain in diameter than did PTA at the initial and late follow-up period; this gain was statistically significant.
Conclusions. Stent placement is more effective than PTA for stenosis of the petrous or cavernous portion of the ICA from the viewpoint of initial and late gain in diameter.
Regulation of aquaporin-4 in a traumatic brain injury model in rats
Authors: Sun Ming-Chieh , Honey Christopher R. , Berk Caglar , Wong Norman L. M. , Tsui Joseph K. C. 
Published: May 2009

Object. Aquaporin-4 (AQP4) plays a significant role in the regulation of brain water homeostasis. In this study the authors investigated the regulation of AQP4 following a focal cortical contusion injury in rats.
Methods. Thirty-three adult male Wistar rats received a focal cortical contusion of the parietal cortex. An additional nine rats underwent a craniectomy, but no trauma was inflicted (sham injury). Animals were killed 1, 4, and 24 hours later. The rat brains were examined for water content by comparing the wet and dry weights of each hemisphere. Aquaporin-4 messenger (m)RNA was measured by reverse transcription—polymerase chain reaction. A ratio of AQP4 mRNA expression in the lesioned hemisphere compared with that in the contralateral control hemisphere was calculated for each animal at the injury site (parietal cortex) and at sites adjacent to (occipital cortex) and distant from the injury (frontal pole cortex).
Brain edema was significantly increased at the injury site. The expression of AQP4 mRNA was significantly increased at the injury site, significantly decreased adjacent to the injury site, and not significantly different at a site distant from the injury. The magnitude of AQP4 mRNA upregulation at the injured parietal cortex correlated with the degree of downregulation in the adjacent occipital cortex.
Conclusions. Data from this study demonstrate that an upregulation of AQP4 occurs at the site of traumatic brain injury and that a downregulation of this molecule occurs adjacent to the site of injury. Understanding the physiology of AQP4 and its regulation following brain injury may allow for the development of novel treatments for cerebral edema that accompanies head injury.
Camptothecin analogs in malignant gliomas: comparative analysis and characterization
Authors: Sampath Prakash , Amundson Eric , Wall Monroe E. , Tyler Betty M. , Wani Mansukh C. , Alderson Lloyd M. , Colvin Michael , Brem Henry , Weingart Jon D. 
Published: May 2009

Object. The authors compared and characterized several new classes of camptothecin (CPT) analogs (a total of 22 drugs) directed against human and murine glioma cell lines in vitro, trying to identify CPT analogs that can be used for local therapy in future clinical trials. Camptothecin is a naturally occurring alkaloid that inhibits the DNA-replicating enzyme topoisomerase I. Moreover, CPT and its analogs have shown promising antitumor activity against both systemic and intracranial neoplasms. Because the CPTs have poor bioavailability and are unable to cross the blood—brain barrier, they may best be delivered to the central nervous system by polymers. The authors have previously shown that local delivery of Na-CPT by implantable polymers prolongs survival in a rat intracranial glioma model. In recent years, a number of newly synthesized CPT analogs have been developed that exhibit more potency and stability than Na-CPT.
Methods. Cytotoxicities of the drugs were tested using modified clonogenic and monotetrazolium assays in three glioma cell lines. A potassium chloride—sodium dodecyl sulfate coprecipitation assay was used to determine the frequency of drug-stabilized cleavable complexes. Of the CPT analogs analyzed, the 10,11-methylenedioxy (MD) class consistently demonstrated the greatest cytotoxicity. Three of these analogs, 10,11-MD-20(RS)-CPT, 10,11-MD-20(S)-CPT-glycinate ester (Gly).HCl, and 9-amino-10,11-MD-20(S)-CPT-Gly, exhibit significantly greater antiproliferative activities than CPT, Na-CPT, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) against all three glioma cell lines. In addition, the 10,11-MD20(RS)-CPT analog induces more cleavable complexes than Na-CPT at every concentration.
Conclusions. The increased potency and greater stability of CPT analogs hold promise for more effective local antitumor treatments against malignant intracranial brain tumors. The greater cytotoxicity of 10,11-MD CPTs in comparison with other CPT analogs as well as CPT, BCNU, or Na-CPT, may present an ideal candidate drug class for development against both primary and metastatic brain tumors.
Convective distribution of macromolecules in the primate brain demonstrated using computerized tomography and magnetic resonance imaging
Authors: Nguyen Tung T. , Pannu Yashdip S. , Sung Cynthia , Dedrick Robert L. , Walbridge Stuart , Brechbiel Martin W. , Garmestani Kayhan , Beitzel Markus , Yordanov Alexander T. , Oldfield Edward H. 
Published: May 2009

Object. Convection-enhanced delivery (CED), the delivery and distribution of drugs by the slow bulk movement of fluid in the extracellular space, allows delivery of therapeutic agents to large volumes of the brain at relatively uniform concentrations. This mode of drug delivery offers great potential for the treatment of many neurological disorders, including brain tumors, neurodegenerative diseases, and seizure disorders. An analysis of the treatment efficacy and toxicity of this approach requires confirmation that the infusion is distributed to the targeted region and that the drug concentrations are in the therapeutic range.
Methods. To confirm accurate delivery of therapeutic agents during CED and to monitor the extent of infusion in real time, albumin-linked surrogate tracers that are visible on images obtained using noninvasive techniques (iopanoic acid [IPA] for computerized tomography [CT] and Gd—diethylenetriamine pentaacetic acid for magnetic resonance [MR] imaging) were developed and investigated for their usefulness as surrogate tracers during convective distribution of a macromolecule. The authors infused albumin-linked tracers into the cerebral hemispheres of monkeys and measured the volumes of distribution by using CT and MR imaging. The distribution volumes measured by imaging were compared with tissue volumes measured using quantitative autoradiography with [14C]bovine serum albumin coinfused with the surrogate tracer. For in vivo determination of tracer concentration, the authors examined the correlation between the concentration of the tracer in brain homogenate standards and CT Hounsfield units. They also investigated the long-term effects of the surrogate tracer for CT scanning, IPA-albumin, on animal behavior, the histological characteristics of the tissue, and parenchymal toxicity after cerebral infusion.
Conclusions. Distribution of a macromolecule to clinically significant volumes in the brain is possible using convection. The spatial dimensions of the tissue distribution can be accurately defined in vivo during infusion by using surrogate tracers and conventional imaging techniques, and it is expected that it will be possible to determine local concentrations of surrogate tracers in voxels of tissue in vivo by using CT scanning. Use of imaging surrogate tracers is a practical, safe, and essential tool for establishing treatment volumes during high-flow interstitial microinfusion of the central nervous system.
Recombinant activated factor VII for cerebral injury—induced coagulopathy in pediatric patients
Authors: Morenski John David , Tobias Joseph D. , Jimenez David F. 
Published: May 2009

✓ Brain injury remains one of the leading causes of death and disability in children. Appropriate therapy involves aggressive management of intracranial pressure (ICP) and cerebral perfusion pressure, which often requires placement of an intraparenchymal ICP monitor or intraventricular catheter. These potentially life-saving interventions require normal coagulation function; however, several factors may lead to coagulopathy in the head-injured patient. Standard therapies, which often include multiple doses of fresh frozen plasma (FFP), have a number of drawbacks when used in the pediatric population. The use of FFP requires time to type and crossmatch, thaw, and administer. It imposes a significant volume load on a child in whom cerebral edema remains a problem. Success in using recombinant activated factor VII (rFVIIa) in the hemophiliac population suggests an alternative therapy.
Three patients suffered severe coagulopathy after cerebral injury. One patient received rFVIIa after repeated doses of FFP had failed to correct the coagulopathy; the other two patients received rFVIIa as the initial therapy. Treatment with rFVIIa consisted of a bolus of 90 µg/kg. Recombinant activated factor VII rapidly corrected the patients' coagulopathies, which allowed placement of intraparenchymal fiberoptic lines and intraventricular catheters to monitor ICP. The patients suffered no complication from the placement of ICP monitoring devices, as demonstrated on computerized tomography scans obtained within 24 hours after placement.
Brain injury—induced coagulopathy may lead to significant secondary injury and delays the invasive monitoring necessary for the aggressive management of intracranial hypertension. Fresh frozen plasma takes time to administer, may require repeated doses of significant volume for the pediatric patient, and may ultimately fail. Preliminary data indicated that rFVIIa provides a rapid and successful correction of coagulopathy in the head-injured patient.
The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings
Authors: Lin Julian , Hanigan William C. , Tarantino Michael , Wang John 
Published: May 2009

Object. In this report the authors describe the use of the hemostatic agent recombinant activated factor VII (rFVIIa) in the perioperative treatment of hemorrhages in the central nervous system that are associated with warfarin therapy.
Methods. Two patients sustained hemorrhages within the spinal canal, and the other two had acute intracranial subdural hematomas. All patients had normal platelet counts, activated partial thromboplastin times, and fibrinogen levels, and all received fresh frozen plasma in conjunction with rFVIIa. The initial international normalized ratios (INRs) ranged from 1.9 to 5.6. Each dose of rFVIIa was 1200 µg, ranging from 16 to 22 µg/kg of body weight. Two patients received two perioperative doses of rFVIIa; the others required just one dose before surgery. The INR normalized within 2 hours of administration of rFVIIa in all patients. There were no thromboembolic complications, and surgical blood loss was less than 100 ml for all operations.
Conclusions. This clinical experience indicates that rFVIIa may be safe and effective as the initial hemostatic agent for rapid reversal of orally administered anticoagulation medications in patients who require urgent neurosurgical intervention.