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Biomedical subjects

F R Sharp

Publications and source records attributed to F R Sharp.

At least 55 records · Page 3Linked to original sources
PubMed1989

Sequential metabolic changes in rat brain following middle cerebral artery occlusion: a 2-deoxyglucose study.

The distribution and time course of altered cerebral metabolism following permanent focal ischemia was studied in rat using the 2-deoxyglucose (2DG) technique. Increased 2DG uptake preceded decreased 2DG uptake and infarction in the caudate putamen and cortex. Decreased 2DG uptake without infarction was observed for 72 h in thalamus and for 24 h in hippocampus (areas remote from the ischemic zones). This study supports the concept of cell excitation as a pathophysiologic process in permanent focal ischemia. The time course of increased metabolism may demarcate the time window of opportunity for the previously demonstrated attenuation of stroke size with inhibition of cell excitation by pharmacologic blockade of excitatory amino acid neurotransmission.

Animals↗
PubMed1989

Regional brain glycogen stores and metabolism during complete global ischaemia.

Microwave fixation in situ was used to assess regional glycogen and glucose stores in normal rat brain. Glycogen levels were highest in the cerebellum and pons/medulla (38.0 and 35.6 nmol/mg protein), and lowest in the striatum and cerebral cortex (17.4 and 23.6 nmol/mg protein respectively). Glucose concentrations paralleled glycogen, ranging from 5.9 to 10.8 nmol/mg protein. Glycogen, glucose, and lactate were measured during complete global ischaemia (decapitation) to assess regional differences in ischaemic metabolism. Those regions which in normal brain contain higher glycogen and glucose stores were found to maintain significantly higher levels of glycogen and glucose for at least 2 minutes of ischaemia. Lactate accumulated to highest levels after 30 minutes of ischaemia in those regions with highest glucose and glycogen stores. Lactate levels did not, however, rise above 90 nmol/mg protein in any brain region, a level well below that considered potentially neurotoxic. The data indicate considerable regional differences in normal and ischaemic glycogen metabolism that might contribute to known regional differences in vulnerability to global ischaemia.

Animals↗
PubMed1989

Regulation of glycogen content in primary astrocyte culture: effects of glucose analogues, phenobarbital, and methionine sulfoximine.

Compounds known to affect glycogen metabolism in vivo or in cell-free preparations were used to investigate the regulation of glycogen content in intact astrocytes cultured from newborn rat cortex. Compounds were added with fresh medium to culture dishes, and astrocyte glucose and glycogen content determined 24 h later. Increasing the medium glucose concentration from 7.5 mM to 30 mM increased cell glycogen content 80%. Addition of 2-deoxyglucose or 3-O-methyl glucose (2.5-10 mM) also increased cell glycogen content, 50-100%, suggesting a regulatory rather than mass action effect of glucose on astrocyte glycogen content. The phosphorylase b inhibitors 2,2',4,4',5,5'-hexabromobiphenyl and riboflavin had no effect on astrocyte glycogen content, consistent with negligible phosphorylase b activity in normal astrocytes. Phenobarbital and L-methionine-DL-sulfoximine (MSO) are both known to induce astrocyte glycogen accumulation in vivo. The addition of phenobarbital (2 mM) had no effect on the glycogen content of cultured astrocytes, suggesting an indirect mechanism for the in vivo effect. MSO at 1 mM, however, induced a 300% increase in glycogen content. The time course of glucose and glycogen content after MSO administration suggests this increase to be the result of slowed glycogenolysis rather than accelerated glycogen synthesis.

3-O-Methylglucose↗
PubMed1989

Suprachiasmatic nucleus: phase-dependent activation during the hibernation cycle.

The suprachiasmatic nucleus (SCN) of the golden-mantled ground squirrel undergoes a phase-dependent change in its accumulation of 2-[14C]deoxy-D-glucose (2-DG) relative to other brain structures during the hibernation cycle. The greatest relative 2-DG uptake (R2DGU) is observed in the SCN during entrance into and during deep hibernation. A circadian fluctuation in R2DGU of the SCN is not evident in the euthermic ground squirrel but can be increased during the subjective day by photic stimulation. An increase in R2DGU by the paraventricular nucleus (PVN) correlates with the increase in R2DGU by the SCN during entrance to hibernation but not with the increase in SCN R2DGU evoked by photic stimulation during euthermia. The periventricular nuclei of the hypothalamus (PEV) also have high levels of R2DGU during the latter phase of the entrance. These observations support the hypothesis that the SCN, PEV, and PVN may play important roles in hibernation and suggest progressive activation of synaptic input to and within the SCN during entrance into this state.

Animals↗
PubMed1988

Expression of c-fos protein in brain: metabolic mapping at the cellular level.

The proto-oncogene c-fos is expressed in neurons in response to direct stimulation by growth factors and neurotransmitters. In order to determine whether the c-fos protein (Fos) and Fos-related proteins can be induced in response to polysynaptic activation, rat hindlimb motor/sensory cortex was stimulated electrically and Fos expression examined immunohistochemically. Three hours after the onset of stimulation, focal nuclear Fos staining was seen in motor and sensory thalamus, pontine nuclei, globus pallidus, and cerebellum. Moreover, 24-hour water deprivation resulted in Fos expression in paraventricular and supraoptic nuclei. Fos immunohistochemistry therefore provides a cellular method to label polysynaptically activated neurons and thereby map functional pathways.

Animals↗
PubMed1988

Common fur and mystacial vibrissae parallel sensory pathways: 14 C 2-deoxyglucose and WGA-HRP studies in the rat.

Stimulation of mystacial vibrissae in rows A,B, and C increased (14C) 2-deoxyglucose (2DG) uptake in spinal trigeminal nucleus pars caudalis (Sp5c) mostly in ventral portions of laminae III-IV with less activation of II and V. Stimulation of common fur above the whiskers mainly activated lamina II, with less activation in deeper layers. The patterns of activation were compatible with an inverted head, onion skin Sp5c somatotopy. Wheatgerm Agglutinin-Horseradish Peroxidase (WGA-HRP) injections into common fur between mystacial vibrissae rows A-B and B-C led to anterograde transganglionic labeling only of Sp5c, mainly of lamina II with less label in layer V, and very sparse label in III and IV. WGA-HRP skin injections appear to primarily label small fibers, which along with larger fibers, were metabolically activated during common fur stimulation. Mystacial vibrissae stimulation increased 2DG uptake in ventral ipsilateral spinal trigeminal nuclei pars interpolaris (Sp5i) and oralis (Sp5o) and principal trigeminal sensory nucleus (Pr5). Common fur stimulation above the whiskers slightly increased 2DG uptake in ventral Sp5i, Sp5o, and possibly Pr5. The most dorsal aspect of the ventroposteromedial (VPM) nucleus of thalamus was activated contralateral to whisker stimulation. Stimulation of the common fur dorsal to the whiskers activated a region of dorsal VPM caudal to the VPM region activated during whisker stimulation. This is consistent with previous data showing that ventral whiskers and portions of the face are represented rostrally in VPM, and more dorsal whiskers and dorsal portions of the face are represented progressively more caudally in VPM. Mystacial vibrissae stimulation activated the contralateral primary sensory SI barrelfield cortex and a separate region in the second somatosensory SII cortex. Common fur stimulation above the whiskers activated a cortical region between the SI and SII whisker activated regions of cortex. It is proposed that this region represented the combined SI and SII common fur regions of somatosensory neocortex. Both whisker and common fur stimulation activated all layers of cortex, with layer IV being most activated followed by II-III, V, and VI. These data indicate that sensory input from the mystacial vibrissae in the adult rat is processed in brainstem, thalamic, and cortical pathways which are predominantly parallel to those which process information from the neighboring common fur sensory receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Decreases of cortical and thalamic glucose metabolism produced by parietal cortex stimulation in the rat.

Parietal cortex stimulation elicited focal decreases as well as increases of brain glucose metabolism in ipsilateral cortex, ipsilateral thalamus, and contralateral cortex of rats in a pattern resembling 'surround inhibition'. It is proposed that parietal stimulation activated inhibitory circuits which decreased cortical and thalamic glucose metabolism. This decrease of cerebral glucose metabolism is important for interpreting brain glucose metabolic studies particularly when metabolic changes do not correlate with changes of neuronal activity.

Animals↗
PubMed1988

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats: reciprocal connections with host thalamus demonstrated with WGA-HRP.

Fetal frontal cortex was transplanted into lesion cavities formed in host motor/sensory cortex of adult rats. Eight to twenty-eight weeks later wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into host thalamus and the brain was sectioned and reacted using a sensitive TMB procedure. A large amount of fine granular WGA-HRP was detected in most transplants. This could represent anterograde transport demonstrating that injured adult host thalamic neurons sprouted axons into fetal cortical transplants. Conversely, none or very few retrogradely labeled pyramidal neurons were present in the transplants. This indicates that pyramidal neurons in transplants either did not sprout into adult host brain or sprouted such short distances that they did not pick up the WGA-HRP. These results are compatible with the hypothesis that high trophic/growth factor levels in newborn or fetal brain and low levels in adults determine the more extensive connections seen in newborn hosts compared with those in adult transplanted hosts. The data are also consistent with the proposal that adult host brains impair axonal growth. Functionally, the data suggest that although corticofugal effects of fetal cortical transplants in adult host brains are likely to be limited, transplants could exert beneficial trophic effects on adult host thalamic neurons.

Animals↗
PubMed1988

Progressive activation of paratrigeminal nucleus during entrance to hibernation.

The paratrigeminal nucleus (Pa5) undergoes a progressive increase in its uptake of 2-[14C]deoxyglucose (2DG) relative to other brain structures during entrance to hibernation in the ground squirrel. This highly significant increase results in the Pa5 becoming the most highly labeled brain region during hibernation, even though it exhibits one of the lowest levels of 2DG uptake in the brain during the nonhibernating state. The progressive activation of the Pa5 observed during entrance is reversed during arousal from hibernation. These observations and the neuroanatomical projections of the Pa5 implicate this nucleus as playing a role in the entrance and maintenance of the hibernating state.

Animals↗
PubMed1988

Intraoral sensation in patients with brainstem lesions: role of the rostral spinal trigeminal nuclei in pons.

Two patients with caudal pontine lesions had diminished intraoral sensation for all modalities sparing facial sensation. A third patient with lateral medullary infarction developed diminished facial pain and temperature sensation sparing intraoral structures. This segregation of intraoral sensation within the brainstem is consistent with animal studies which show that the rostral spinal trigeminal nuclei in the caudal half of the pons play an important role in intraoral and dental sensation.

Adult↗
PubMed1988

Neuronal changes in fetal cortex transplanted to ischemic adult rat cortex.

Fetal cortex from 16- and 17-day-old embryonic rats was transplanted into the parietal cortex of 12 adult rats rendered ischemic by temporary intraluminal occlusion of the middle cerebral artery. Ischemic injury in the host cortex adjacent to all nine surviving transplants was demonstrated with hematoxylin and eosin and cresyl violet strains. Nicotidamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical studies revealed a normal number of NADPH-d-positive neurons, whereas acetylcholinesterase (AChE) staining revealed many more AChE-positive neurons in the transplants compared to the host parietal cortex. This could be due to: 1) selective survival of AChE neurons in the transplants compared to the host cortex; 2) increased expression of AChE in transplanted neurons; 3) induction of AChE in normally AChE-negative neurons; or 4) decreased transport of the AChE enzyme from the perikarya to fibers in surviving transplanted neurons. Many fibers positive for AChE and NADPH-d crossed between the host and transplant, although fiber density in the transplants was less than in normal host cortex. These results should encourage future investigation of whether similar transplants improve neurological function following experimental stroke.

Acetylcholinesterase↗
PubMed1987

The regional distribution of glycogen in rat brain fixed by microwave irradiation.

Glycogen concentrations were measured by fluorescence enzymatic assay in rat brains fixed by focused microwave irradiation Regional glycogen concentrations varied 2.5 fold, ranging from 27.1 nmol glucosyl units/mg protein in the striatum to 52.3 nmol/mg protein in the cerebellum and 69.9 nmol/mg protein in the pons-medulla; other regions were intermediate in concentration. Since glycogen is contained primarily within astrocytes, this regional variation may reflect regional differences in astrocyte energy metabolism.

Animals↗
PubMed1987

Investigations of the anal sphincter before and after restorative proctocolectomy.

Twenty-eight patients who underwent sphincter-saving proctocolectomy and formation of an ileoanal reservoir had clinical evaluation of resting and maximal anal sphincter pressures and perfused catheter manometry. The clinical estimate of resting tone, heretofore believe to be a good predictive parameter of postoperative function, was inaccurate. This suggests the advisability of manometric evaluation. There were significant changes in sphincter pressures postoperatively. Operation did not effect the preoperative electromyographic findings of the puborectalis muscle and external sphincter in our small postoperative population. The mechanism by which operation might influence these parameters has been discussed. Factors such as parity and the descending perineum syndrome may effect continence. Due to the length of time the sphincter is required to function in these patients and the multiplicity of factors involved, we believe that long-term studies are needed.

Adult↗
PubMed1987

Axotomy increases NADPH-diaphorase staining in rat vagal motor neurons.

Left cervical vagotomy increased NADPH-diaphorase (NADPH-d) histochemical staining in neuronal perikarya of the ipsilateral dorsal motor nucleus of the vagus (dmnX) and the rostral part of the nucleus ambiguus (nAmb). This effect appeared by 2 days, was maximal around 10 days, and declined by 30 days after vagotomy. Light and dark stained perikarya occurred in dmn X ipsilateral to the vagotomy which could not be explained on the basis of the biochemical or transmitter content of these neurons. It is unlikely that the increases of NADPH-d activity resulted from changes in cholinergic transmission since vagotomy is known to decrease cholinergic enzyme function. Since vagotomy increased both the glucose metabolic rate and NADPH-d staining of dmnX and nAmb in these experiments, it is more likely that these effects represent regenerative metabolic responses to axotomy.

Animals↗
PubMed1987

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. II. VIP-, somatostatin-, and NPY-immunoreactive neurons.

Fetal frontal cortex transplants that survived 2-9 months in cavities in adult rat motor/sensory cortex were processed for vasoactive intestinal polypeptide (VIP), somatostatin 14 (SS), and neuropeptide Y (NPY) immunocytochemistry, and NADPH-diaphorase (NADPH-d) histochemistry. All transplants had surviving VIP, SS, NPY, and NADPH-d neuronal perikarya and fibers with normal adult morphology. The number of peptidergic neurons within transplants, however, often appeared to be less than that in equivalent areas of host cortex. Most transplanted SS and VIP neuronal perikarya did not migrate to form the laminae characteristic of normal cortex. A few transplants had SS and VIP cells arranged in laminae in which the VIP processes were parallel to one another and perpendicular to one transplant surface, approximating normal host neocortex. VIP, NPY, and SS fibers crossed between host brains and transplants, suggesting that peptide host-transplant interactions are possible. All adult host cortical and most transplanted NPY neurons colocalized with NADPH-d. The failure of some transplanted NPY neurons to express NADPH-d suggests these transplanted cells may be functionally impaired, but that they can survive without the NADPH-d enzyme.

Animals↗
PubMed1987

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. I. NADPH-diaphorase neurons.

Fetal frontal cortex from 18-d-old embryonic rat brain was transplanted into cavities of juvenile host motor/sensory cortex. Two to seven months later, sections were reacted for NADPH-diaphorase (NADPH-d) enzyme histochemistry. NADPH-d-positive neurons survived in 11 of 13 grafts. All but one of the transplants had reduced numbers of these neurons, although in 3 transplants the reductions were moderate and not statistically significant. The distribution and morphology of NADPH-d neurons within most grafts was comparable to that of NADPH-d neurons in normal host cortex. At the margin of the 2 transplants with no NADPH-d neuronal perikarya, NADPH-d fibers crossed from host to transplant as far as a millimeter into the transplant, and on rare occasions, the host neurons that gave rise to these fibers were identified. This suggests that host-transplant interactions are possible. One transplant had an abnormally large number of NADPH-d-positive neurons and fibers, possibly due to selective survival of these neurons. The data reported here for NADPH-d in cortical transplants may also apply to neuropeptide Y (NPY), since nearly all neocortical NPY neurons also contain NADPH-d.

Animals↗
PubMed1986

Regional differences of brain glucose metabolic compensation after unilateral labyrinthectomy in rats: a [14C]2-deoxyglucose study.

A unilateral labyrinthectomy was performed on anesthetized adult albino rats. Brain [14C]2-deoxyglucose (2DG) uptake was measured autoradiographically 3.5 h to 20 days later and compared to sham-operated controls. In the vestibular nuclei (nn.) of labyrinthectomized subjects, large left-right differences of 2DG uptake occurred, which decreased over time. The equalization of vestibular nuclear 2DG uptake paralleled behavioral compensation of body, neck and head postural abnormalities, and known equalization of vestibular nuclear cell firing rates during compensation. There was a small difference of 2DG uptake in medial and lateral vestibular nn. 20 days after lesions when animals had a residual head tilt and tonic eye deviation. In the oculomotor nn., trochlear nn. and interstitial n. of Cajal, large left-right differences of 2DG uptake occurred, which did not change over time. The higher 2DG uptake in these nn. occurred ipsilateral to the labyrinthine lesion and did not correlate with the onset and cessation of nystagmus. The persistent asymmetry did appear to correlate with ipsilateral downward and contralateral upward eye deviation which continued for long periods after the lesion. We hypothesize that the non-compensating metabolic asymmetry in the oculomotor and trochlear nn. could be due to lesioned otolithic input to the vestibular nn. which relays to trochlear and oculomotor nn.

Animals↗