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K D Barron

Publications and source records attributed to K D Barron.

At least 19 recordsLinked to original sources
PubMed1994

Persistent neuroleptic-induced rigidity and dystonia in AIDS dementia complex: a clinico-pathological case report.

Patients with AIDS dementia complex (ADC) appear to have an increased likelihood of developing acute onset parkinsonism and dystonia when treated with dopamine antagonists. It has been hypothesized, based on clinical evidence, that hypersensitivity to these drugs in ADC is probably related to direct invasion of the basal ganglia by the HIV virus and a secondary alteration in dopaminergic mechanisms. We report the first pathological description of a patient with ADC who developed acute onset, generalized rigidity and dystonia after a brief trial of low dose neuroleptic therapy administered for psychotic symptoms. An unusual clinical feature of this case was the persistence of his movement disorder. Pathological examination revealed a generalized encephalitic process with substantial neuronal loss observed primarily in the medial and lateral globus pallidus. Correlation with a current model of basal ganglia pathophysiology and other disorders with pallidal lesions is discussed. Clinical and pathological features of this case confirm the previous contention and indicate that dopamine antagonists should be utilized with extreme caution in patients with ADC.

AIDS Dementia Complex↗
PubMed1994

Platelet morphology in Parkinson's disease: an electron microscopic study.

There are no peripheral diagnostic markers for Parkinson's disease (PD). However, recent studies of platelets in PD patients indicate that mitochondrial and monoamine oxidase function may be abnormal. This investigation examines platelets in PD from a morphological standpoint utilizing transmission electron microscopy (EM). Fourteen PD patients (seven treated, seven untreated) and seven age matched controls had platelets separated from other blood components, fixed in a standardized fashion and examined by EM. Platelets (in the activated form because they were collected in glass tubes) were evaluated at magnifications of 15,000x and 40,000x. Abnormalities observed in treated and untreated PD patients included the presence of numerous large intracytoplasmic vacuoles formed from the open canalicular system. Morphometric examination performed at 40,000x magnification indicated that the mean area of vacuoles and the cytoplasmic volume percent of platelets occupied by vacuoles were significantly greater in PD (p < 0.05) than controls. However, differences observed between treated and untreated PD groups suggest that these changes could be caused by the disease or the treatment or both. No abnormalities were found in relation to mitochondria, storage granules and glycogen. From EM assessment, we conclude that platelets in PD are morphologically abnormal.

Adult↗
PubMed1993

Report of congenital anaplastic astrocytoma discovered in a newborn.

Reports of congenital anaplastic astrocytoma have been rare, representing less than 2% of all brain tumors. We present a case of a congenital anaplastic astrocytoma discovered during the first 24 hours after delivery. A recent literature review found 12 additional cases since 1972. The presenting signs, most common findings on neuroimaging, treatment, and outcome are examined.

Brain Neoplasms↗
PubMed1992

Myelin deficiency in female rats due to a mutation in the PLP gene.

Myelin deficiency (md) in female rats due to a mutation in the X-linked proteolipid protein (PLP) gene is caused by X-chromosome monosomy. Cytogenetic analysis revealed a single X karyotype [41,X(md/0)]. An immunocytochemical, electron microscopic, and biochemical study was performed on male and female md rats. The central nervous system (CNS) of the female md rat [41,X(md/0)] revealed the same total lack of PLP as the CNS of the affected male littermate [42,XY(md/Y)]. Immunocytochemistry for myelin basic protein (MBP), myelin-associated glycoprotein (MAG), and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) revealed "islands" of myelin sheath-like reaction product in both. Electron microscopy showed great paucity of compact myelin sheaths in 41,X(md/0) and 42,XY(md/Y). Reduced levels of MPB, MAG, and CNP were confirmed for both sexes but MAG and CNP were substantially higher in 41,X(md/0). Sexual differentiation of the brain may account for the observed differences since normal female reproductive organs are present in the md female rat.

Animals↗
PubMed1990

Perineuronal glial responses after axotomy of central and peripheral axons. A comparison.

In each of 6 mature rats, unilateral rubrospinal tractotomy and hypoglossal neurectomy were done at one operative sitting. Paired operated animals were killed by formaldehyde and ethanol-acetic acid perfusion 3, 14 and 28 days later. One pair of unoperated control rats was perfused also. All rats were injected i.p. with [3H]thymidine 24 h before death. Immunohistochemical methods were applied to paraffin sections to visualize glial fibrillary acidic protein (GFAP) and transferrin in astrocytes and oligodendroglia, respectively. Microglia were demonstrated by both lectin-binding and histoautoradiographic methods. Neuroglia and nerve cells were counted in hematoxylin-eosin and azure B stains. Cell areas and the RNA concentration of hypoglossal neurons were determined by the Zeiss Image Scan System. Three days after hypoglossal neurectomy, increased astroglial staining (GFAP) and microglial hyperplasia (radiolabeled nuclei) were evident in the ipsilateral hypoglossal nucleus (HN). Microglial hyperplasia waned rapidly after 3 days and microglial numbers decreased. However, astroglial hypertrophy, demonstrable by GFAP staining, persisted 4 weeks postoperatively when astroglial processes were concentrated in a perineuronal position. Oligodendroglia were unaltered. In contrast to the HN, the axotomized red nucleus (RN) contained few radiolabeled microglia while a slight increase in GFAP-positive astroglial processes was seen only in animals killed 28 days postoperatively. Again, oligodendroglia were unchanged. In neither HN nor RN did axotomy cause nerve cell death. Although axotomized rubral neurons atrophy and become depleted of RNA, no statistically significant changes in somal size and RNA content of axotomized hypoglossal neurons occurred. The apparent absence of a neuroglial response of putatively supportive nature in the environs of axotomized rubral neurons may relate to their failure to regenerate. The neuroglial response likely is originated by the axotomized neuron and its absence may be an innate defect in the reaction of intrinsic neurons to axonic severance. Somas of axotomized peripherally projecting nerve cells appear to have the capacity to summon a neuroglial response.

Animals↗
PubMed1990

Axonal regrowth in the amyelinated optic nerve of the myelin-deficient rat: ultrastructural observations and effects of ganglioside administration.

It has been postulated that myelin degradation products may inhibit regrowth of mammalian central axons and that central nervous system (CNS) myelin and oligodendrocytes may constitute a "nonpermissive substrate" for axonal growth. To address these issues, we utilized an X-linked rat mutant, myelin-deficient or md. In the optic nerve of this mutant, 40 days and more postnatally, normal myelin is absent and oligodendrocytes are few (Dentinger et al. Brain Res. 344:255-266, 1985). Twenty-eight days before sacrifice, we operated on four groups of 50-day-old md rats and age-matched normal littermates according to the following protocols: 1) unilateral intraorbital optic nerve crush; 2) beginning within 1 hour of nerve crush, daily intraperitoneal injection of GM1 ganglioside (20 mg/kg) dissolved in phosphate-buffered saline (PBS); 3) daily intraperitoneal injection of PBS alone, also begun within 1 hour of nerve crush; 4) severance of the optic nerve immediately behind the papilla 16 or 21 days after the primary crush lesions. Additionally, normal and md rats were killed 4 and 14 days after unilateral optic nerve injury. Nerves of unoperated md rats and their normal littermates were also processed. In the operated animals that did not receive GM1, ultrastructural analysis 4, 14, and 28 days after lesioning revealed that md optic nerves contained significantly greater numbers of regenerating axons, including growth cones and varicosities, than nerves of normal rats. Notably, 28 days postoperatively, (group 1), regenerating axons were still abundant in md nerve, whereas, in nerves of normally myelinated littermates, axonal numbers were diminished markedly. Regenerating optic axons of both md and normally myelinated rats were oriented by linear astrocytic arrays and often were enclosed by astrocytic cytoplasm. In normal littermates, GM1 administration (group 2) induced a significant increase in the number of axons within the operative lesion. Paradoxically, GM1 inhibited the ordinarily robust regeneration of md axons. PBS-injected md and normal rats (group 3) showed no significant differences from noninjected, operated animals. Severance of the nerve at the papilla (group 4) 7-12 days before sacrifice confirmed the origination of axonal regrowth by retinal ganglion cells. The data provide in vivo support for a role of myelin breakdown products or the secretory products of oligodendroglia in the inhibition of regenerative axonal sprouting within mammalian CNS.

Animals↗
PubMed1990

Neurological evaluation of chronic headache patients: is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.

Adult↗
PubMed1990

Brain anti-cytoxic edema agents.

The work described in this chapter has indicated that improved outcome from an experimental head injury model can be achieved by drugs which are non-diuretic derivatives of loop diuretics, namely indanyl and fluorenyl compounds which are derivatives of ethacrynic acid. These drugs were originally identified by us on the basis of their efficacy in inhibiting [K+]-stimulated, HCO3(-)-dependent swelling of brain cerebrocortical slices. Swelling of glial cells (astrocytes) has long been known to be associated with such slice swelling and astrocyte swelling is a major locus of cytotoxic or cellular brain edema. Qualitative and quantitative electron microscope studies have shown that L644,711, a particularly effective member of the fluorenyl class of drugs, inhibits astrocytic swelling associated with an experimental animal head injury model. We have suggested that astrocytic swelling in pathological states may be partly due to activation of Cl-/HCO3- and Na+/H+ exchange systems driven by increased astrocytic intracellular hydration of CO2, and recent work has indeed shown that the ability of the indanyl and fluorenyl drugs to inhibit brain slice swelling and protect against head injury correlates closely with their ability to inhibit Cl-/HCO3- exchange. All these data suggest that astrocytic swelling, which seems to precede neuronal degeneration and breakdown of the blood-brain barrier, is deleterious and that prevention of such swelling can lead to effective therapy. We have used primary astrocytic cultures to explore reasons why astrocytic swelling could be harmful. Exposing such astrocytes to hypotonic medium causes rapid swelling with a slower return to normal volume in the continued presence of hypotonic medium, a process known as regulatory volume decrease or RVD. Such RVD is associated with marked release of several amino acids, including L-glutamate. L644,711 and other Cl-/HCO3- transport inhibitors such as SITS and furosemide, but not the selective Na+ + K+ + 2Cl- co-transport inhibitor bumetanide, inhibit such swelling-induced release of L-glutamate. Thus, L644,711 and other drugs may be effective in promoting recovery from head injury and other pathological states in which astrocytic swelling occurs either by initially preventing the swelling or inhibiting the release of excitotoxic excitatory amino acids if swelling does occur, perhaps depending at what time the drug is given.

Animals↗
PubMed1989

Cytological and cytochemical (RNA) studies on rubral neurons after unilateral rubrospinal tractotomy: the impact of GM1 ganglioside administration.

The rubrospinal tract (RST) was cut unilaterally at C2-3 segment in 21 rats that were killed 3, 7, 10, 14, 28, 60, and 90 days later. Additionally, 14 rats, killed 14 or 28 days after lesioning, were treated postoperatively by daily intraperitoneal injections of GM1 ganglioside. Six unoperated, untreated rats served as controls. In untreated animals, axotomized neurons of the magnocellular division of the red nucleus (RN) exhibited cytoplasmic, nuclear, and nucleolar atrophy 7-10 days postoperatively. Atrophy progressed through the 90th postoperative day. Regression analyses disclosed a bimodal pattern to cytoplasmic and nucleolar atrophy, with an initial rapid phase changing to a slower but progressive mode from 14 days postoperatively. Nuclear atrophy proceeded in a unimodal manner. GM1 treatment did not affect these atrophic processes. Neuronal loss did not occur in the axotomized RN through the 60th postoperative day. Axotomized neurons of untreated rats showed significant and progressive reductions in mean somal (cytoplasmic) and nucleolar RNA from, respectively, the 7th and 14th postoperative day. GM1 partly prevented these RNA losses. Both in treated and untreated rats, spinal cord lesions contained many axonal sprouts 2 to 4 weeks after surgery, but newly generated axons did not traverse the rostro-caudal extent of any lesion.

Animals↗
PubMed1989

Astrocytic swelling in traumatic-hypoxic brain injury. Beneficial effects of an inhibitor of anion exchange transport and glutamate uptake in glial cells.

Swelling of brain slices is shown to occur in response to elevated potassium levels or glutamate, which is accompanied by astrocytic swelling. Cl-/HCO3- anion exchange inhibitors, such as SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid) or furosemide, but not the specific cotransport inhibitor bumetanide, inhibit swelling or increased ion uptake in rat brain slices caused by elevated potassium although there were marked species differences in sensitivity. A novel anion exchange inhibitor, L-644,711, inhibits swelling and increased ion uptake caused by glutamate in rat and cat brain slices, as well as inhibiting [3H]glutamate uptake in primary rat astrocyte cultures. Possible mechanisms of action of the inhibitors are discussed. L-644,711 was also found to be effective in promoting recovery from a trauma plus hypoxia head injury model in cats. Marked perivascular astrocytic swelling is associated with this head injury model, and L-644,711 also inhibited such astroglial swelling as determined ultrastructurally. The significance of these findings in relation to possible connections between astrocytic swelling and brain pathology is discussed.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1988

Ultrastructural features of a brain injury model in cat. I. Vascular and neuroglial changes and the prevention of astroglial swelling by a fluorenyl (aryloxy) alkanoic acid derivative (L-644,711).

We present qualitative and quantitative ultrastructural observations on the changes induced in neuroglia and blood vessels of gray matter of cat brain by an experimental acceleration-deceleration injury which, when used alone, causes negligible morbidity and mortality, but, when combined with systemic hypoxia, leads to coma and delayed death in approximately 50% of experimental subjects. An increase in the proportion of neuropil occupied by astrocytic cytoplasm is detectable qualitatively in layer Vb of pericruciate cortex 20 min after injury without hypoxia, and is maximal (22%, as measured morphometrically, vs 11.4% in controls) 40 min afterward. Near-normal values (14.1%) are obtained 100 min following the insult. If trauma is succeeded 40 min later by a 60-min period of hypoxia, there is prolongation of astrocytic edema and other neuroglial accompaniments of the traumatic lesion, such as aggregation of nuclear nucleoprotein granules and, in astrocytes, fusion of rosette ribosomes and enlargement of mitochondria. A decrease in luminal area occurs in capillaries 40 min after trauma applied alone. Hypoxia without trauma leads to a significant increase in capillary luminal area, which, however, is abolished when trauma precedes the hypoxic interlude. Intravenous injection of a non-diuretic, fluorenyl derivative (L-644,711) of (aryloxy)alkanoic acid loop diuretics, completely prevents the astrocytic swelling ordinarily present 40 min after acceleration-deceleration injury. Also, L-644,711 improves mortality and morbidity scores in cats subjected to trauma with hypoxia. We suggest that astroglial swelling may be a critical step in the evolving pathology of this head injury model and its prevention, as by L-644,711 administration, may have relevance to the treatment of cerebral edema in human head injury and other clinical disorders accompanied by astrocytic swelling.

Animals↗
PubMed1988

Comparative immunocytochemistry of Pelizaeus-Merzbacher disease, the jimpy mouse, and the myelin-deficient rat.

Patients with Pelizaeus-Merzbacher disease (PM), hemizygous mice with the jimpy mutation (jp/Y), and hemizygous rats with X-linked myelin deficiency (md/Y) share a profound lack of proteolipid protein (PLP) in their central nervous systems (CNS). The peripheral nervous system is normal. These X-linked disorders are associated with or actually caused by the lack of normal oligodendrocytes. Vibratome sections of brain were incubated with antisera to myelin basic protein (MBP), myelin-associated glycoprotein (MAG), 2':3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) (EC 3.1.4.37), PLP, a synthetic PLP-peptide, glial fibrillary acidic protein (GFAP), and transferrin. Reaction product was developed by sequential incubation with biotinylated second antibodies, the avidin-biotin-peroxidase complex (ABC), and diaminobenzidine (DAB) plus hydrogen peroxide as chromogenic substrates. In PM, jp/Y and md/Y, islands of myelin-like structures were revealed by antisera to MBP, MAG, and CNP. Reaction product after application of anti-PLP was absent. Reaction product after anti-PLP-peptide was restricted to infrequent bizarre cells possibly representing abnormal oligodendroglia. The lack of oligodendrocytes in jp/Y and md/Y could also be confirmed by immunocytochemistry for transferrin.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1988

Neurons of layer Vb of rat sensorimotor cortex atrophy but do not die after thoracic cord transection.

Albino rats six weeks (wk) of age underwent transection of the spinal cord at the level of the seventh thoracic vertebra. They were killed ten wk later by several schedules of formaldehyde-glutaraldehyde, formaldehyde and formaldehyde-ethanol-acetic acid perfusion-fixation. Layer Vb of the sensorimotor cortex, the site of origin of corticospinal axons severed by the operation, was searched by light and electron microscopic methods for evidence of neuronal necrosis. Cord-transected rats were compared with control, unoperated animals of identical age. Nerve cell death was not evident to qualitative study, although shrunken, deeply-staining neurons of artefactitious origin occurred capriciously in paraffin sections when fixation was initiated with a dilute formaldehyde-glutaraldehyde solution. Quantitative light and electron microscopic studies were also negative for indications of neuronal death. However, mild somal atrophy could be substantiated for layer Vb neurons of cord-transected rats by light microscopic, morphometric methods. Neuronal atrophy was unaccompanied by qualitative or quantitative ultrastructural alterations. Subcellular organelles and the per cent of neuronal plasma membrane apposed by axosomatic boutons were unchanged. Neuroglia and neuronal processes always had a normal electron microscopic appearance.

Animals↗
PubMed1987

Abnormalities of central axons in a dysmyelinative rat mutant.

The absence of normal myelin from the CNS of the dysmyelinative rat mutant, md, is associated with axonal abnormalities including organelle-poor and organelle-rich spheroids (OPS and ORS, respectively), wrinkling of the axolemma, persistence of glycogen aggregates and vacuoles in cerebellar mossy fiber terminals, and coalescence of synaptic vesicles in terminal boutons of the nucleus interpositus. OPS have a special predilection for medullary pyramid and the axons of Purkinje cells and further differ from ORS in their possession of nematosomes and in their lack of neurofilaments, microtubules, and degenerating mitochondria. Purkinje cells of md fail to increase in size after 30 days postnatal age and, unlike these neurons in normal neonatal rats, may have massed or dispersed granules of cytoplasmic glycogen which persist for at least 86 days postnatally. Morphometric study of axons of medullary pyramid and cervical corticospinal tract at 19-43 days of age shows a shift in frequency to axons of smaller size in md, as compared to age-matched controls, except that approximately 1% of md axons are larger than any encountered in controls. Finally, the pyramidal axons of md at 43 days of age have a significantly larger area of axoplasm occupied by mitochondria than obtains for the control condition. We conclude that the described abnormalities are secondary to the lack of a myelin investment and/or the loss of oligodendrocytes.

Animals↗
PubMed1987

Regional variation in the levels of transferrin in the CNS of normal and myelin-deficient rats.

Transferrin (Tf), the iron mobilization protein, is synthesized mainly in the liver. Recently, both Tf and a mRNA for Tf have been demonstrated in oligodendrocytes in the rat brain. The present study used a biochemical assay for determining the levels of Tf in various brain regions of normal rats compared with the level of those obtained from rats with a genetic mutation characterized by an almost complete failure to develop myelin. In myelin-deficient (md) rats, no Tf-positive oligodendrocytes were seen immunohistochemically in the gray or white matter of the CNS. Quantitatively, levels of Tf throughout the CNS of the md rat were decreased to approximately 5% of the normal values despite a normal hepatic synthetic rate. In the normal rat brain, the cerebellum contained the highest concentration of Tf, followed by the pons, the cerebral cortex, and the caudate-putamen, with the latter two sites being similar. Regional variation in the amount of Tf was in general agreement with published reports on the variation of iron and Tf receptor levels in the CNS. Immunohistochemical examination with antiserum to galactocerebroside (a myelin-specific lipid) was used for extending biochemical reports that glycolipid-synthesizing enzymes are deficient in md rats. No immunostaining in the md rat was observed following immunoreaction for galactocerebroside, whereas white matter oligodendrocytes were intensely marked in the normal rat. Robust astrogliosis was present in both the gray and white matter of the md rats. It is not known at present whether the ability to accumulate Tf is necessary for oligodendrocytic survival or if Tf accumulation is more directly related to myelinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mitochondrial encephalomyopathy and partial cytochrome c oxidase deficiency.

A 52-year-old man had slowly progressive weakness and wasting of limb-muscles, sensorineural hearing loss, and complex partial seizures. CT showed cerebral atrophy, but he was not demented. Muscle biopsy showed ragged-red fibers and decreased histochemical stain for cytochrome c oxidase. Biochemical studies showed decreased cytochrome c oxidase activity in crude muscle extracts and in isolated mitochondria (44 and 30% of normal), while other mitochondrial enzymes were normal. A comparable decrease of immunologically reactive enzyme protein was shown by immunotitration with antibodies against human heart cytochrome c oxidase. Partial defects of cytochrome c oxidase may cause adult-onset, slowly progressive mitochondrial encephalomyopathies.

Atrophy↗
PubMed1986

Qualitative and quantitative ultrastructural observations on retinal ganglion cell layer of rat after intraorbital optic nerve crush.

Rat retinal ganglion cell layer (GCL) was examined ultrastructurally 1-180 days after intraorbital crushing of one optic nerve. It was confirmed quantitatively that axotomized ganglion cells lost cisternal membranes of the rough endoplasmic reticulum (RER) and showed disintegration of Nissl bodies and ribosomal rosettes 3 days postoperatively. Between 60 and 180 days after neurotomy there was partial reversion of the RER towards normal. At postoperative intervals of 14-60 days, chromatin aggregation became conspicuous and some nuclei were prominently furrowed and contained electron-dense inclusions. Concurrently, profiles of dead ganglion cells were encountered. Mean mitochondrial area increased in axotomized neurons but mitochondrial density declined, while the Golgi apparatus, lamellar specializations of the RER and the size of nuclei did not change significantly. Cytoplasmic atrophy was profound, however. Small nerve cells of the GCL appeared morphologically distinct from ganglion cells and did not undergo appreciable alteration. A decline in neuronal density, approximating 35%, occurred between the third and seventh postoperative day and progressed slowly thereafter. Neuronal density was 32% of normal 180 days postoperatively. A temporary increase in glial density 3-28 days after operation was due to microglial hyperplasia. Müller cell and astrocytic processes hypertrophied, infiltrated nerve fibre bundles, and surrounded and intruded into neuronal somata. Bundles of unmyelinated small axons, invested by astrocytes and basal lamina, were present within the necrotic cavity of the lesioned nerve 28-90 days postoperatively and had cytologic features of regenerative axonal sprouts. We conclude that intraorbital optic nerve crush is followed by a noteworthy degree of regenerative axonal sprouting which occurs and persists against a background of slow but relentless decline in the retinal ganglion cell population. This slow decline follows a rapidly-sustained loss of approximately one-third of the axotomized retinal ganglion cells during the first postoperative week. Intraorbital, as opposed to intracranial, injury of the optic nerve appears, paradoxically, to induce both a greater degree of ganglion cell death and a greater amount of regenerative axonal sprouting. Cytologic changes in axotomized retinal ganglion cells resemble those described for other populations of mammalian intrinsic neurons subjected to like injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗