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F R Sharp

Publications and source records attributed to F R Sharp.

At least 37 records · Page 2Linked to original sources
PubMed1990

Hypoxia-ischemia induces heat shock protein-like (HSP72) immunoreactivity in neonatal rat brain.

The expression of heat shock protein immunoreactivity in rat brain was evaluated in a model of neonatal hypoxia-ischemia. One-week-old rats were subjected to left carotid artery coagulation and exposure to 8% O2/92% N2 for 2 h (moderate injury) or 3.5 h (severe injury). Animals were sacrificed 1, 12 and 24 h after the hypoxic insult. Cells immunoreactive for the 72 kDa heat shock protein (HSP72) were observed in ipsilateral cortex as early as 1 h after the termination of the hypoxia. After 12 h, neurons in the ipsilateral hippocampus and cortex stained intensely for HSP72 immunoreactivity in the moderately injured group. In the severely injured brains, bilateral staining was observed in neurons and vessels of the hippocampus and cortex. Therefore, cells containing HSP72 immunoreactivity may serve as an early marker for neuronal injury from hypoxia-ischemia in the neonatal rat brain and more importantly may illustrate previously unrecognized areas of central nervous system vulnerability.

Animals↗
PubMed1990

Neural transplantation using temperature-sensitive immortalized neural cells: a preliminary report.

Current approaches to neural transplantation--adrenal medullary and fetal brain--suffer from limitations in tissue availability, cellular uniformity, and general applicability. The system described here uses temperature-sensitive immortalized clonal neural cells to address these limitations. Cerebellar cells, immortalized with a temperature-sensitive tumor virus, are transformed at 34 degrees C, but differentiate at 38 degrees C. The cells were genetically engineered to express beta-galactosidase, providing a tag to study their fate in the host. The cells were then successfully transplanted to the cerebellum of adult rats.

Animals↗
PubMed1990

c-fos proto-oncogene expression in astrocytes associated with differentiation or proliferation but not depolarization.

Expression of the c-fos proto-oncogene in rat neocortical astrocytes in culture was examined using Northern blotting and immunocytochemistry. Marked induction of c-fos mRNA in astrocytes was observed after treatment with epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), dibutyryl cyclic AMP (db-cAMP), and phorbol diester (TPA; 12-O-tetra-decanoylphorbol 13-acetate), which are known to induce the proliferation or differentiation of astrocytes. Increase of c-fos protein immunoreactivity (IR) was obtained after treatment with fetal calf serum, EGF, bFGF, db-cAMP and TPA. High concentrations of calcium ionophore A23187, which were lethal to cultured astrocytes, also increased c-fos protein-IR. Treatment with lower concentrations of calcium ionophore (which slightly increase Ca2+ uptake), high K+ and nerve growth factor had no detectable effect on c-fos expression. These results show that depolarization does not induce c-fos in astrocytes and suggest that c-fos may play a role in differentiation and proliferation of astrocytes.

Animals↗
PubMed1990

Light induces a Fos-like nuclear antigen in retinal neurons.

Fos, the product of the proto-oncogene c-fos, is a nuclear phosphoprotein thought to participate in transcriptional regulation of target genes. To explore the synaptic induction of Fos and related proteins in vivo, Fos immunohistochemistry was performed in the rabbit retina. Dark-adapted retinas had virtually no Fos immunostaining. Retinas of dark-adapted rabbits that were exposed to 3 Hz diffuse flashing white light for 1 h and sacrificed 2 h later displayed nuclear Fos immunostaining in a minority of neurons. These included presumptive amacrine cells of the inner nuclear layer and either displaced amacrine cells or ganglion cells of the ganglion cells of the ganglion cell layer. Therefore, Fos or a related antigen is expressed in a subset of retinal neurons in response to light and is presumably involved in regulating gene expression of these cells to respond to alterations in synaptic activity.

Animals↗
PubMed1990

The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury.

Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.

Animals↗
PubMed1990

A semiautomated method for measuring brain infarct volume.

An accurate, reproducible method for determining the infarct volumes of gray matter structures is presented for use with presently available image analysis systems. Areas of stained sections with optical densities above that of a threshold value are automatically recognized and measured. This eliminates the potential error and bias inherent in manually delineating infarcted regions. Moreover, the volume of surviving normal gray matter is determined rather than that of the infarct. This approach minimizes the error that is introduced by edema, which distorts and enlarges the infarcted tissue and surrounding white matter.

Animals↗
PubMed1990

Light regulates expression of a Fos-related protein in rat suprachiasmatic nuclei.

Mammalian circadian rhythmicity is endogenously generated by a pacemaker in the suprachiasmatic nuclei and precisely entrained to the 24-hr day/night cycle by periodic environmental light cues. We show that light alters the immunoreactive levels of a transcriptional regulatory protein, Fos, in the suprachiasmatic nuclei of albino rats. Photic regulation of Fos immunoreactivity does not occur in other retino-recipient brain areas except for the intergeniculate leaflet, which appears to be involved in mediating some of the complex effects of light on expressed circadian rhythms. Our results point to a promising new functional marker for the cellular effects of light and suggest that the expression of Fos or a related nuclear protein may be part of the mechanism for photic entrainment of the circadian clock to environmental light/dark cycles.

Animals↗
PubMed1990

Glutamate increases glycogen content and reduces glucose utilization in primary astrocyte culture.

The glycogen content of primary cultured astrocytes was approximately doubled by incubation with 1 mM L-glutamate or L-aspartate. Other amino acids and excitatory neurotransmitters were without effect. The increase in glycogen level was not blocked by the glutamate receptor antagonist kynurenic acid but was completely blocked by the glutamate uptake inhibitor threo-3-hydroxy-D,L-aspartate and by removal of Na+ from the medium. Incubation with radiolabeled glucose and glutamate revealed that the increased glycogen content was derived almost entirely from glucose. Glutamate at 1 mM was also found to cause a 53 +/- 12% decrease in glucose utilization and a 112 +/- 69% increase in glucose-6-phosphate levels. These results suggest that the glycogen content of astrocytes is linked to the rate of glucose utilization and that glucose utilization can, in turn, be affected by the availability of alternative metabolic substrates. These relationships suggest a mechanism by which brain glycogen accumulation occurs during decreased neuronal activity.

Animals↗
PubMed1990

Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion.

The methionine analogue methionine sulfoximine was administered to 10 rats 24 hours before occlusion of the proximal left middle cerebral artery. Three days later the rats were decapitated and the brain infarct volumes were compared with those in 10 control rats that received saline before middle cerebral artery occlusion. The mean volume of the infarct in the cerebral cortex was reduced by 33% in the group treated with methionine sulfoximine (p less than 0.01). This protective effect may be mediated by a presynaptic mechanism; methionine sulfoximine profoundly inhibits brain glutamine synthetase, thereby interrupting the astrocyte-neuron glutamate shuttle and impairing neuronal glutamate release. Methionine sulfoximine also increases brain glycogen stores, and this increased energy reserve may benefit penumbral tissue during the peri-infarct period. Further study of the mechanisms by which methionine sulfoximine decreases infarct volume could lead to new therapeutic approaches for stroke.

Animals↗
PubMed1990

Induction of fos-like immunoreactivity in hypothalamic corticotropin-releasing factor neurons after adrenalectomy in the rat.

To identify brain sites responding to the removal of corticosterone feedback by adrenalectomy (ADX), rat brains were processed for fos immunocytochemistry 1, 3, and 7 days after ADX, sham-ADX, or no surgery using a polyclonal antiserum to fos residues 132-154. Compared to SHAM, ADX rats exhibited strong fos-like immunoreactivity (FLI) only in the parvocellular neurons of the paraventricular hypothalamic nuclei (PVN) 1, 3, and 7 days after surgery. Replacement with a corticosterone pellet at the time of adrenalectomy (ADX + B) prevented this increase in PVN FLI in three of four rats at 1 day, all rats at 3 days, and two of seven rats 7 days after surgery; 100 micrograms/ml corticosterone in the drinking water for 2 days before perfusion reversed ADX-induced increases in PVN FLI in 7-day ADX rats. Providing 25 micrograms/ml corticosterone in the drinking water to ADX rats for 5 days after surgery did not prevent expression of PVN FLI, even though this dose has been shown to normalize morning basal ACTH levels in ADX rats. Virtually all parvocellular PVN neurons expressing FLI after ADX costained for CRF. Some parvocellular neurons also expressed both fos and vasopressin. In all rats, many brain regions expressed FLI that was not related to adrenalectomy. We conclude that the changes in neuronal FLI correlate with demonstrated changes in neuroendocrine activity after ADX; however, suppression of ADX-induced FLI may require higher replacement levels of corticosterone than inhibition of ADX-induced ACTH secretion.

Adrenalectomy↗
PubMed1990

14C-2-deoxyglucose uptake in the ground squirrel brain during entrance to and arousal from hibernation.

Neuronal activity underlying various phases of the mammalian hibernation cycle was investigated using the 14C-2-deoxyglucose (2DG) method. Relative 2DG uptake (R2DGU) values were computed for 96 brain regions across 7 phases of the hibernation cycle: euthermia, 3 body temperature (Tb) intervals during entrance into hibernation, stable deep hibernation, and 2 Tb intervals during arousal from hibernation. Multivariate statistical techniques were employed to identify objectively groups of brain regions whose R2DGU values showed a similar pattern across all phases of hibernation. Factor analysis revealed that most of the variability in R2DGU values for the 96 brain regions across the entire cycle could be accounted for by 3 principal factors. These factors could accurately discriminate the various phases of hibernation on the basis of the R2DGU values alone. Three hypothalamic and 3 cortical regions were identified as possibly mediating the entrance into hibernation because they underwent a change in R2DGU early in entrance into hibernation and loaded strongly on one of the principal factors. Another 4 hypothalamic regions were similarly identified as possibly causally involved in the arousal from hibernation. These results, coupled with characteristic changes in ordinal rank of the 96 brain regions in each phase of hibernation, support the concept that mammalian hibernation is an active, integrated orchestration of neurophysiological events rather than a state entered through a passive process.

Animals↗
PubMed1989

c-fos expression and (14C) 2-deoxyglucose uptake in the caudal cerebellum of the rat during motor/sensory cortex stimulation.

Fos, the protein product of the c-fos gene, is induced in neurons in response to a variety of stimuli. In order to see if Fos could be used to map activity in the brain, the pattern of Fos staining was compared to the pattern of (14C) 2-deoxyglucose (2DG) uptake in the seventh and eighth lobules of the cerebellum during electrical stimulation of the cerebral cortex. Electrical stimulation of hindlimb motor/sensory cortex of awake rats increased 2DG uptake in the contralateral and ipsilateral cerebellum. The largest increases occurred in granule cell patches in the contralateral copula pyramidis (Cop P) and pyramis (P), the hemispheric and vermal portions of the eighth cerebellar lobule, respectively. The granule cell patches formed parasagittal bands that extended short distances mediolaterally, and extended long distances anteroposteriorly over much of the Cop P. Forelimb motor/sensory cortex stimulation increased 2DG uptake bilaterally in the seventh, paramedian (PM) cerebellar lobule. The greatest increases occurred in the granule cell layer contralateral to the stimulation. These and the above results generally agree with classical studies that localize forelimb on the seventh lobule anterior to the hindlimb on the eighth lobule. However, hindlimb cortical stimulation activated parts of the PM, and forelimb cortical stimulation activated portions of the rostral Cop P. In general, nonoverlapping portions of Cop P and PM were activated during the two types of cortical stimulation. These results are consistent with a fractured somatotopy (Welker and Shambes, '85) in which nonadjacent body parts are consistently represented in adjacent granule cell patches on each lobule, with the fractured somatotopy being different for every lobule. No region of cerebellum expressed Fos in unstimulated, electrode implanted, control subjects. However, following 15 minutes of electrical stimulation of hindlimb cortex, Fos was expressed 4 hours later in patches of granule cell nuclei in Cop P and P. These patches of Fos immunostained granule cells occurred in similar locations in Cop P to the patches of highest glucose metabolism observed with the 2DG method. Zones of Purkinje cell nuclei also expressed Fos. These Purkinje cell zones were often directly over similar sized granule cell patches in P. In the hemisphere however, the zones of Purkinje cells in ventrolateral Cop P expressing Fos only partially overlapped underlying granule cell patches that expressed Fos. Moreover, Fos was not unduced in any Purkinje cells adjacent to the Fos- stained granule cell patch in dorsolateral Cop P.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Induction of the c-fos gene product in rat forebrain following cortical lesions and NGF injections.

Neocortical lesions and NGF injections into neocortex induce the immunostaining of Fos, the c-fos gene product, in neuronal nuclei in ipsilateral cortex, and amygdala. Adjacent structures including hippocampus, septal nuclei, globus pallidus, and thalamus were unaffected. It is hypothesized that trophic molecules or other chemicals are released at the injury site and these induce the c-fos gene in cells throughout the ipsilateral hemisphere. Fos induction might mediate metabolic or plasticity responses to the focal injury.

Animals↗
PubMed1989

Function and quality of life results after ileal pouch surgery for chronic ulcerative colitis and familial polyposis.

The aim of this study was to assess gastrointestinal function and quality of life, including occupational, social, and sexual function, in 75 patients who underwent pelvic pouch construction between November 1984 and May 1988 at our institution. Complications occurred in 45 percent of patients after pouch construction and in 17 percent after ileostomy closure. One patient died from sepsis caused by an anastomotic leak after ileostomy closure. The most common complication was a pouch-anal anastomotic stricture (22 percent), and the complication with the greatest potential morbidity was pouch-anal dehiscence (8 percent), which was highly predictive of pouch failure. Functional results were assessed by questionnaire during the 3-month period after ileostomy closure in all 58 patients who successfully attained intestinal continuity. A second assessment was performed at 15 +/- 11 months after ileostomy closure in 52 patients whose continuity had been restored for longer than 3 months. In an overall assessment, 94 percent of all patients with restored intestinal continuity (73 percent of entire patient group) rated the pouch as being superior to a permanent ileostomy and 92 percent (71 percent of entire group) would go through another pouch procedure. These results support the continued recommendation of this procedure as an acceptable alternative to proctocolectomy and permanent ileostomy in patients with ulcerative colitis or familial polyposis.

Adenomatous Polyposis Coli↗
PubMed1989

Heat shock proteins as markers of neural injury.

Systemic or intracerebral injections of kainic acid induced immunoreactivity for the 72 kDa heat shock protein (HSP72) in individual neurons of the rat brain in patterns matching the known histopathology of the particular injury. HSP72 immunostaining was also induced in and around areas of infarction following experimental strokes. These results suggest that HSP72 immunocytochemistry may be used as a marker of cellular injury in the mammalian brain.

Animals↗
PubMed1989

Trigeminal nerve section induces Fos-like immunoreactivity (FLI) in brainstem and decreases FLI in sensory cortex.

Transecting the infraorbital nerve to the rat whiskers induced Fos-like immunoreactivity (FLI) in lamina I and II neuronal nuclei of the spinal trigeminal nucleus pars caudalis (Sp5c). The Fos-like immunostaining persisted for several weeks. The prolonged expression of FLI in Sp5c could be related to persistent activity in the sectioned nerve, or to trophic effects of injured ganglion neurons on brainstem cells. We postulate that Fos and related proteins may be involved in mediating alterations in gene expression associated with relatively long-term CNS adaptations to peripheral nerve injuries. Surprisingly, FLI decreased in contralateral sensory cortex, mainly in layers 2, 3 and 6, up to several days after the lesion. These decreases of cortical FLI may be due to decreased sensory neuronal activity, and/or to reducing the trophic influence of thalamic inputs on cortical neurons.

Animals↗