bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary motor neurons fail to up‐regulate voltage‐gated sodium channel Nav1.3/brain type III following axotomy resulting from spinal cord injury
Authors: Hains Bryan C. , Black Joel A. , Waxman Stephen G. 
Published: October 2002

AbstractEpilepsy occurs in a small proportion of patients with spinal cord injury (SCI), but whether it is due to concomitant traumatic head injury or to changes in cortical motor neurons secondary to axotomy within the spinal cord is not known. Nav1.3/brain type III sodium channel expression is up‐regulated following peripheral axotomy of dorsal root ganglion (DRG) and facial motor neurons, but, to date, Nav1.3 expression has not been examined in upper (cortical) motor neurons following axotomy associated with SCI. In the present study, we examine Nav1.3 expression in upper motor neurons within rat primary motor cortex following midthoracic (T9) dorsal column transection, which severs the axons of those cells. Axotomized pyramidal cells were identified by retrograde transport of fluorogold. Immunolabeled cells were confined to layer V of the primary motor cortex and exhibited low levels of Nav1.3 staining. After axotomy, no significant changes were detected in Nav1.3 density or distribution in injured or uninjured cells, compared with control brains, in contrast to up‐regulation of Nav1.3 in ipsilateral DRG neurons after sciatic nerve transection. These results do not preclude a role for voltage‐gated sodium channels in post‐SCI epilepsy but suggest that up‐regulated expression of Nav1.3 channel is not involved. © 2002 Wiley‐Liss, Inc.
Single cell activity patterns of pedunculopontine tegmentum neurons across the sleep‐wake cycle in the freely moving rats
Authors: Datta Subimal , Siwek Donald F. 
Published: October 2002

AbstractMicroinjections of the excitatory amino acid, L‐glutamate into the cholinergic cell compartment of the pedunculopontine tegmentum (PPT) of the rat induces both wakefulness and/or rapid eye movement (REM) sleep depending on the glutamate dosage. However, no studies have systematically recorded the electrical activity of these cells in the freely moving rat across the sleep‐wake cycle. In this study, we have recorded the spontaneous activity patterns of single PPT cells (n = 70) in the freely moving rat across the sleep‐wake cycle. PPT neurons were classified into three groups based on patterns in their spontaneous activity. The first group of cells (12.86%) was more active during REM sleep than they were during wakefulness or slow‐wave sleep (SWS). The second group of cells (60.0%) was more active during REM and wakefulness than during SWS. The firing rate of the third group of cells (27.14%) did not change as a function of behavioral state. This study also demonstrated that the level of activity within the cholinergic cell compartment of the PPT during SWS drops to 7.4% of that observed during wakefulness and that during REM sleep it changes to 65.5% of wakefulness levels. These findings indicate that in the freely moving rat, the discharging of PPT neurons correlates with wakefulness and REM sleep. Additionally, these neurons may be an integral part of the brainstem wakefulness and REM sleep‐generating mechanisms in the rat. © 2002 Wiley‐Liss, Inc.
Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S‐nitrosothiols and with changes in glutathione levels
Authors: Calabrese Vittorio , Scapagnini Giovanni , Ravagna Agrippino , Bella Rita , Foresti Roberta , Bates Timothy E. , Giuffrida Stella Anna‐Maria , Pennisi Giovanni 
Published: October 2002

AbstractNitric oxide (NO) is hypothesized to play a role in the immunopathogenesis of multiple sclerosis (MS). Increased levels of NO metabolites have been found in patients with MS. Peroxynitrite, generated by the reaction of NO with superoxide at sites of inflammation, is a strong oxidant capable of damaging tissues and cells. Inducible NO synthase (iNOS) is up‐regulated in the CNS of animals with experimental allergic encephalomyelitis (EAE) and in patients with MS. In this study, Western blots of cerebrospinal fluid (CSF) from patients with MS demonstrated the presence of iNOS, which was absent in CSF from control subjects. There was also NOS activity present in both MS and control CSF. Total NOS activity was increased (by 24%) in the CSF from MS patients compared with matched controls. The addition of 0.1 mM ITU (a specific iNOS inhibitor) to the samples did not change the activity of the control samples but decreased the NOS activity in the MS samples to almost control levels. The addition of 1 mM L‐NMMA (a nonisoform specific NOS inhibitor), completely inhibited NOS activity in CSF from control and MS subjects. Nitrotyrosine immunostaining of CSF proteins was detectable in controls but was greatly increased in MS samples. There were also significant increases in CSF nitrate + nitrite and oxidant‐enhanced luminescence in MS samples compared with controls. Additionally, a significant decrease in reduced glutathione and significant increases in oxidized glutathione and S‐nitrosothiols were found in MS samples compared with controls. Parallel changes in NO metabolites were observed in the plasma of MS patients, compared with controls, and accompanied a significant increase of reduced glutathione. These data strongly support a role for nitrosative stress in the pathogenesis of MS and indicate that therapeutic strategies focussed on decreasing production of NO by iNOS and/or scavenging peroxynitrite may be useful in alleviating the neurological impairments that occur during MS relapse. © 2002 Wiley‐Liss, Inc.
Calpain and calpastatin expression in primary oligodendrocyte culture: Preferential localization of membrane calpain in cell processes
Authors: Ray Swapan K. , Neuberger Timothy J. , Deadwyler Gail , Wilford Gloria , DeVries George H. , Banik Naren L. 
Published: October 2002

AbstractThe cellular localization of calpain is important in understanding the roles that calpain may play in physiological function. We, therefore, examined calpain expression, activity, and immunofluorescent localization in primary cultures of rat oligodendrocytes. The mRNA expression of m‐calpain was 64.8% (P = 0.0033) and 50.5% (P = 0.0254) higher than that of μ‐calpain and calpastatin, respectively, in primary culture oligodendrocytes. The levels of mRNA expression of μ‐calpain and calpastatin were not significantly different. As revealed by Western blotting, cultured oligodendrocytes contained a 70 kD major band identified by membrane m‐calpain antibody, a 80 kD band recognized by cytosolic m‐calpain antibody, and calpastatin bands ranging from 45 to 100 kD detected by a calpastatin antibody. Calpain activity in oligodendrocytes was determined by Ca2+‐dependent 71.2% degradation of endogenous myelin basic protein compared with control; this activity was inhibited significantly (P = 0.0111) by EGTA and also substantially by calpeptin. Localization of calpain in cultured oligodendrocytes revealed strong membrane m‐calpain immunofluorescence in the oligodendrocyte cell body and its processes. In contrast, the cytosolic antibody stained primarily the oligodendrocyte cell body, whereas the processes were stained very weakly or not at all. These results indicate that the major form of calpain in glial cells is myelin (membrane) m‐calpain. The dissimilar localization of cytosolic and membrane m‐calpain may indicate that each isoform has a unique role in oligodendrocyte function. © 2002 Wiley‐Liss, Inc.
Expression of glutamate receptor subtypes in the spinal cord of control and mnd mice, a model of motor neuron disorder
Authors: Mennini Tiziana , Bigini Paolo , Ravizza Teresa , Vezzani Annamaria , Calvaresi Novella , Tortarolo Massimo , Bendotti Caterina 
Published: October 2002

AbstractWe studied the expression and distribution of glutamate receptor subtypes in the spinal cord of mnd mice, a model of motor neuron disorders and neuronal ceroid lipofuscinosis, and control mice using immunocytochemistry and in situ hybridization. The constitutive subunit of the NMDA ionotropic glutamate receptor, NMDAR1, was expressed in all neurons of the grey matter and was not modified in the spinal cord of mnd mice in either its normal or phosphorylated form. The immunoreactivity of GluR2, but not its mRNA, was increased mainly in the substantia gelatinosa both in presymptomatic and in 8‐month‐old symptomatic mice, suggesting compensatory changes aimed at reducing the Ca2+ permeability of the receptor channel. In spinal cord of mnd mice, mRNA, and protein levels of GluR3 were low only at the symptomatic stage, possibly as a consequence of motor neuron dysfunction. This was not due to motoneuron degeneration, because the number of choline acetyltransferase (ChAT) immunopositive lumbar motor neurons and the ChAT activity in the spinal cord and hind leg muscles of symptomatic mnd mice were no different from control mice. GluR4 mRNA was increased throughout the grey matter, presumably in relation to the marked microglia activation reported in the grey matter of the lumbar spinal cord in mnd mice. These changes in ionotropic glutamate receptors may alter glutamatergic neurotransmission and play some role in the pathology of mnd mice. © 2002 Wiley‐Liss, Inc.
Modeling Alzheimer's disease immune therapy mechanisms: Interactions of human postmortem microglia with antibody‐opsonized amyloid beta peptide
Authors: Lue Lih‐Fen , Walker Douglas G. 
Published: October 2002

AbstractThe induction of an antibody response to amyloid beta (Aβ) peptide has become a strategy for the treatment of Alzheimer's disease (AD). This has proven effective in reducing the plaque burden in transgenic mice that develop Aβ plaques similar to human AD patients. The mechanism for enhanced clearance of Aβ is partly due to the interaction of immunoglobulin Fcγ receptor‐expressing microglia and specific antibody‐opsonized Aβ deposits. This interaction can stimulate Fcγ receptor‐mediated phagocytosis, but also results in inflammatory activation of these cells. Consequently, interaction of microglia with antibody‐antigen complexes could exacerbate the existing inflammation in the brains of AD patients. In this study, we used substrate‐bound Aβ and cultured human microglia from AD and non‐demented cases to model interaction of microglia and antibody‐opsonized plaques in AD brains. Enhanced production of tumor necrosis factor‐α, macrophage colony stimulating factor, interleukin‐10, and superoxide ions was detected. We also demonstrated enhanced uptake of opsonized Aβ by microglia, which was reduced significantly in the presence of excess IgG, indicative of the involvement of Fcγ receptor‐mediated mechanisms. Human microglia were shown in this study to express mRNA for Fcγ receptors I, IIa, IIb, and III. The expression of Fcγ receptor II was augmented by proinflammatory stimulation. These results suggest that initial interactions of human microglia with antibody‐opsonized amyloid could result in increased inflammation. The consequence of this on inflammatory pathology in AD brains needs to be considered before immunization is used as a strategy for treating AD. © 2002 Wiley‐Liss, Inc.
Effects of intrauterine inflammation on developing rat brain
Authors: Bell Michael J. , Hallenbeck John M. 
Published: October 2002

AbstractDamage to the white matter in the brain during development can lead to cerebral palsy (CP), a heterogeneous group of clinical syndromes that results in life‐long disorders of movement and posture. Periventricular leukomalacia (PVL) is a pathological process within the white matter characterized by oligodendrocyte loss and is associated with the development of CP. Clinically, CP and PVL are associated with intrauterine infection and inflammation, but mechanisms involved are not well understood. We developed a model of intrauterine inflammation in Lewis and Fischer 344 rats to study the effects of intrauterine inflammation on developing glia. Pregnant rats were intracervically injected with lipopolysaccharide (LPS) at 15 days of gestation (E15) and a dose of LPS that caused low fetal mortality was determined. At E20, treated fetuses had increased TUNEL+ nuclei and tumor necrosis factor (TNF)‐α‐immunoreactive areas within the brains. In a second series of animals allowed to survive until postnatal day 21 (PND 21), immunostaining was performed against several glial markers. Staining for the oligodendrocyte‐specific proteins 2′, 3′‐cyclic nucleotide phosphodiesterase (CNP) and myelin proteolipid protein (PLP) was decreased in treated pups compared to shams within the corpus callosum, a white matter structure used as a representative area of developing white matter. Treated pups had activated astrocytes lining cerebral blood vessels, as observed by glial fibrillary acidic protein (GFAP) staining, while sham pups did not. Activated microglia were not detected using OX42 as a cell marker. Our model of intrauterine inflammation causes increased TUNEL and TNF‐α staining early after injury, suggesting increased apoptotic cell death, possibly by cytokine‐related mechanisms. © 2002 Wiley‐Liss, Inc.
Type‐2 astrocyte‐like cells are more resistant than oligodendrocyte‐like cells against non‐N‐methyl‐D‐aspartate glutamate receptor‐mediated excitotoxicity
Authors: Yamaya Yoko , Yoshioka Akira , Saiki Shinji , Yuki Natsuko , Hirose Genjiro , Pleasure David 
Published: October 2002

AbstractGlutamate causes excitotoxicity via non‐N‐methyl‐D‐aspartate (NMDA) glutamate receptors (GluR) in oligodendrocytes. Because both oligodendrocytes and type 2 astrocytes are differentiated from oligodendrocyte‐type 2 astrocyte (O‐2A) progenitor cells, we investigated whether astrocytes are also vulnerable to non‐NMDA GluR‐mediated excitotoxicity. For these studies, oligodendrocyte‐like cells (OLC) and type 2 astrocyte‐like cells (2ALC) were derived from CG‐4 cells, an immortalized rat O‐2A progenitor cell line. About 50% of 2ALC were positive for glial fibrillary acidic protein and 90% were positive for A2B5, verifying that these cells have an type 2 astrocytic phenotype. A 24‐hr exposure of OLC to 2 mM kainate, an activator of non‐NMDA GluR, caused cell damage as shown by the release of lactate dehydrogenase. The extent of kainate‐induced OLC damage was increased by cyclothiazide. In contrast, exposure of 2ALC to 2 mM kainate alone did not induce injury, though mild 2ALC injury was elicited by exposure to 2 mM kainate plus 100 μM cyclothiazide. Furthermore, we found that the kainate induced Ca2+ uptake by 2ALC was 27.5% of that induced by kainate in OLC. Finally, both OLC and 2ALC expressed non‐NMDA GluR subunit mRNAs, including GluR2, GluR3, GluR4, GluR6, GluR7, KA1, and KA2, but quantitative Western blot analysis revealed higher immunodetectable GluR2 and lower immunodetectable GluR3 and GluR4 in 2ALC than in OLC. Together, these results suggest that astrocytes are relatively resistant to non‐NMDA GluR‐mediated excitotoxicity because they have a higher expression of GluR2 and lower expression of GluR3 and GluR4. © 2002 Wiley‐Liss, Inc.
In vivo model for visualizing flap microcirculation of ischemia‐reperfusion
Authors: Ichioka Shigeru , Minh Trinh Cao , Shibata Masahiro , Nakatsuka Takashi , Sekiya Naomi , Ando Joji , Harii Kiyonori 
Published: October 2002

AbstractSince ischemia‐reperfusion injury continues to be a major problem in reconstructive microsurgery, improvement of experimental models is still desirable. We developed a model that allows direct visualization of flap microcirculation in mice by intravital microscopic techniques. A newly designed skinfold chamber was installed on the dorsum of mice, and microcirculation was inspected with an intravital microscope. An island flap, nourished by the deep circumflex iliac arteries, was elevated after implantation of the chamber, allowing visualization of the microcirculation in the island flap. The island flap was exposed to global ischemia by clamping the pedicles, and the clamps were then released to allow reperfusion. Various microcirculatory responses induced by ischemia‐reperfusion were visualized. This model accurately simulated the clinical situation in reconstructive surgery and successfully realized chronic visualization of the flap microcirculation in vivo. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:304–310 2002
Absorptive properties of synovium harvested from the carpal tunnel
Authors: Sud Vipul , Tucci Michelle A. , Freeland Alan E. , Smith William T. , Grinspun K. 
Published: October 2002

AbstractIschemia‐induced reperfusion injury seems to play an important role in the pathophysiology of “idiopathic” carpal tunnel syndrome (CTS). The common final pathway in this developmental sequence is thought to be an intermittent increase in interstitial pressure, leading to degenerative changes in the flexor tenosynovium and fibrotic changes in the perineural tissue. We hypothesize that this concurrently leads to alteration in the physical properties of the synovium, leading to its rapid and persistent swelling. A prospective study was conducted on synovial tissue obtained from 27 CTS patients. The in vitro synovial absorption rate of CTS patients was significantly higher in the first hour compared to controls (n = 7). This difference was maintained up to 5–6 h, albeit at a slower rate. Rapid absorption and retention of fluid by the synovium led to increased interstitial pressure and nerve compression, resulting in early and persistent manifestation of symptoms in sensitized patients. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:316–319 2002
Monitoring free flaps using laser‐induced fluorescence of indocyanine green: A preliminary experience
Authors: Holm C. , Tegeler J. , Mayr M. , Becker A. , Pfeiffer U.J. , Mühlbauer W. 
Published: October 2002

AbstractIn a prospective, clinical study, the clinical utility of indocyanine green for intraoperative monitoring of free tissue transfer was evaluated. The study comprised 20 surgical patients undergoing elective microsurgical procedures. Indocyanine green angiography was performed intraoperatively, immediately after flap inset, and the operating team was blind to the fluoremetric findings. Thereafter, postoperative monitoring was done exclusively by clinical examination (color, temperature, time for recapillarization, and bleeding after puncture). Final outcome was compared with results of perioperative indocyanine (ICG)‐imaging, and classified either as total flap loss, partial flap loss, or successful tissue transplantation. A total of 2 (10%) complications was recorded, and included one partial and one total flap loss. Both complications were detected by intraoperative ICG imaging. Another case of intraoperative subclinical arterial spasm at the place of microvascular anastomosis was revealed by dynamic ICG‐videography. This flap did not develop postoperative complications. In conclusion, evaluation of perfusion by ICG imaging is feasible in all kinds of microsurgical flaps, irrespective of the type of tissue. Even though not meeting all the criteria of an ideal monitoring device, significant additional information can be obtained. In this study, cases with arterial spasm, venous congestion, and regional hypoperfusion were revealed by intraoperative ICG‐videography. There was a strong correlation between intraoperative findings and clinical outcome. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:278–287 2002
Neurotrophins and their receptors in early axonal regeneration along muscle‐vein‐combined grafts
Authors: Pagnotta Alessia , Tos Pierluigi , Fornaro Michele , Gigante Antonio , Geuna Stefano , Battiston Bruno 
Published: October 2002

AbstractExperimental and clinical studies have shown that a vein segment filled with skeletal muscle used to bridge a peripheral nerve defect (muscle‐vein‐combined graft) leads to good nerve repair. However, the molecular basis of the nerve fiber regeneration process along this type of graft still remains to be elucidated. The aim of this study was to verify the expression of two neurotrophins, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF), as well as their receptors, trkA and p75, in an early stage of axonal regeneration in muscle‐vein‐combined grafts. Severed rat sciatic nerves were repaired by means of 1‐cm‐long muscle‐vein‐combined grafts and withdrawn immediately after surgery (control grafts) and 5 days after surgery. Longitudinal sections of grafts were immunostained by means of the following antibodies: anti‐NGF, anti‐BDNF, anti‐trkA, and anti‐p75. An anti‐glial fibrillar acid protein (anti‐GFAP) antibody was used to recognize Schwann cells. Results showed the presence of a number of GFAP‐positive Schwann cells inside the muscle‐vein grafts. Many of these cells reacted for NGF, BDNF, and p75, but not trkA. In control grafts, i.e., immediately after surgery, no immunostaining was detected for any of the antibodies used in this study. These observations suggest that, very early after surgery, the muscle‐vein‐combined graft offers to growing axons an environment particularly favorable for regeneration, providing us with a possible explanation for the efficacy of this grafting technique for peripheral nerve repair. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:300–303 2002
Effect of long‐term application of epinephrine on rat skin vasculature: Experimental study
Authors: Karacaoğlu Ercan , Çermik Hakan , Yurdun Türkan , Zienowicz Richard J. 
Published: October 2002

AbstractAs a potent vasoconstrictor, epinephrine is used ubiquitously in plastic surgery. It is typically delivered subcutaneously in very low concentrations over a brief time interval. We are aware of no reports describing the long‐term release of epinephrine as an independent agent to the soft tissues for the purpose of causing prolonged local vasoconstriction. This study was designed to address two goals: first, to investigate the effect of long‐term local release of epinephrine from a drug delivery system on rat abdominal skin vasculature; secondly, to evaluate the pharmacological properties of this drug delivery system (DDS). Thirty male Sprague‐Dawley rats, weighing 300–400 g, were included in the study. Animals were subdivided into two groups of 15 each. Group A (control group) and Group B (experimental group) were treated with saline and epinephrine‐loaded microspheres (msps), respectively. The manufacturing process and formulation studies of the DDS are described. In vivo assays revealed a 7‐day sustained release of epinephrine. After 7 days, neither residual nor supraphysiologic release of epinephrine was shown with high‐performance liquid chromatography (HPLC). Histological studies with hematoxylin‐eosin and periodic acid Schiff revealed a statistically significant increase in number of vessels as well as their diameter and wall thickness (P <0.05). Epinephrine release via this msp/DDS predictably induces local vasoconstriction over a time sequence known to be optimally associated with hypoxia and promotion of vascular augmentation. This model can be valuable in sustaining hemostasis during long‐lasting (more than a few hours) surgical procedures by its long‐acting vasoconstructive effect. The system's ability to intentionally cause vascular augmentation also bodes great potential in flap and graft surgery. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:288–294 2002