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Biomedical subjects

J McCulloch

Publications and source records attributed to J McCulloch.

At least 235 records · Page 13Linked to original sources
PubMed1982

Local cerebral glucose utilization in hypothermic and hyperthermic rats.

Local rates of glucose utilization in 38 regions of the CNS were measured in conscious, lightly restrained rats during normothermia (rectal temperature, 37.4 +/- 0.1 degrees C, hypothermia (31.8 +/- 0.1 degrees C), and hyperthermia (40.2 +/- 0.3 degrees C). In 34 of the 38 regions examined (the four exceptions being primary auditory nuclei in the lower brainstem), a significant relationship could be demonstrated between the rate of glucose utilization and body temperature. The magnitude of temperature-related alterations in glucose use displayed considerable regional heterogeneity. In hypothermic rats the reductions in glucose use were proportionately most marked (reduced 35-50% from normothermic) in thalamic nuclei, extrapyramidal and motor areas, septohippocampal formation, and some areas of neocortex and white matter; they were least pronounced in anterior hypothalamus (reduced by 13%), habenula (by 16%), and amygdala (by 22%). In hyperthermic rats, significantly increased glucose utilization was observed in only 16 of the 38 areas examined (e.g., hypothalamus, hippocampus, extrapyramidal system, and raphe nucleus), whereas in a number of major areas (such as the neocortex and thalamus) glucose use was minimally altered with hyperthermia. The regional heterogeneity in the alterations in glucose utilization suggests that caution must be exercised in the interpretation of autoradiographic 2-deoxyglucose investigations in which body temperature disturbances occur.

Animals↗
PubMed1982

Effects of the putative GABAergic agonists, muscimol and THIP, upon local cerebral glucose utilisation.

The dose-dependent effects of two putative gamma-aminobutyric acid (GABA)-ergic agonists, muscimol and 4,5,6,7-tetrahydroisoxazolo(4,5-e)-pyridin-3-ol (THIP), upon local cerebral glucose utilisation in 60 discrete regions of the CNS have been examined in conscious rats using the [14C]2-deoxyglucose quantitative autoradiographic technique. The intravenous administration of muscimol (0.15-5 mg/kg) and THIP (1-10 mg/kg) resulted in a heterogeneous pattern of significantly reduced glucose utilisation throughout the CNS. The regional hierarchy of changes in glucose utilisation was similar for both muscimol and THIP in all regions (with the exception of the superior colliculus), with muscimol being approximately six times more potent in all regions investigated. The regions in which glucose utilisation was extremely sensitive to change, displaying reductions of approximately 40% following muscimol (1.5 mg/kg) or THIP (10 mg/kg) administration, included all layers of the neocortex (frontal, sensory motor, posterior parietal, primary auditory and visual cortices), the lateral portion of the caudate nucleus, and some thalamic nuclei (lateral geniculate body, mediodorsal and ventrolateral nuclei). Regions displaying more modest reductions in glucose utilisation, approximately 20% following muscimol (1.5 mg/kg) and THIP (10 mg/kg) administration, included most extrapyramidal regions (substantia nigra, pars compacta and reticulata, globus pallidus, subthalamic nucleus, medial portion of the caudate nucleus), a number of cortical and subcortical limbic areas (cingulate and olfactory cortices, hippocampus, nucleus accumbens, anterior thalamus), and medial raphe nucleus. In contrast, in a large number of regions (including cerebellum and related nuclei such as the inferior olivary, red and vestibular nuclei, white matter, pontine reticular formation, hypothalamus, lateral habenula and amygdala), there were only minimal (approximately 10%) reductions in glucose utilisation following muscimol (1.5 mg/kg) and THIP (10 mg/kg) administration. In no region of the CNS was a significant increase in glucose utilisation observed with any concentration of either muscimol or THIP. The regional distribution of alterations in glucose utilisation following muscimol and THIP administration, which does not correspond to the known topography of GABAergic neurones and receptors, provides a comprehensive description of the functional alterations, as reflected in rates of glucose utilisation, that occur in conscious rats after systemic administration of these two putative GABAergic agonists.

Analgesics↗
PubMed1982

Antagonism by (D-Pro2, D-Trp7,9)-substance P of the cerebrovascular dilatation induced by substance P.

The effects of (D-Pro2, D-Trp7,9)-substance P, a structural analogue of substance P, were examined in two models on cerebrovascular responses to substance P(SP) in cats; in vitro using segments of the middle cerebral artery and in situ by microapplication of the peptides close to pial arterioles. (D-Pro2, D-Trp7,9)-SP in concentrations up to 6.6 x 10(-6) M was without significant effect upon isolated middle cerebral arteries under normal conditions and in arteries contracted with prostaglandin F2 alpha. SP caused concentration-dependent relaxations of middle cerebral arteries contracted by prostaglandin F2 alpha (mean +/- SE; EC50: 2.0 +/- 1.6 x 10(-9) M). The presence of (D-Pro2, D-Trp7,9)-SP shifted the concentration-response curve of SP towards higher concentrations without significantly effecting the maximum response of the arteries to SP. A relaxation by 24.2 +/- 4.0% (n = 6) was obtained in prostaglandin F2 alpha contracted arteries by increasing the potassium concentration with 2 mM in the buffer solution. This response to potassium was unaltered in the presence of 6.6 x 10(-6)M of (D-Pro2, D-Trp7,9)-SP (25.0 +/- 7.1%, n = 5). Perivascular microapplication of SP around individual pial arterioles in situ effected dose-dependent increases in vascular calibre (mean response 14.5 +/- 2% with SP, 10(-7)M). The concomitant perivascular administration of (D-Pro2, D-Trp7,9)-SP (6.6 x 10(-6)M), which alone did not alter the arteriolar calibre, attenuated significantly the cerebrovascular response to SP (mean response 1.5 +/- 3.2%). On the basis of the agonist-antagonist relation found, these observations point to the possibility of a specific SP receptor site in cerebral arteries and arterioles.

Animals↗
PubMed1982

Feline cerebral veins and arteries: comparison of autonomic innervation and vasomotor responses.

1. The innervation of feline cerebral (pial) vessels by nerve fibres containing noradrenaline, substance P or vasoactive intestinal polypeptide (VIP) has been examined using the Falck-Hillarp histo-fluorescence method and immunohistochemical techniques. Cerebral veins were shown to be innervated by nerve fibres containing noradrenaline, substance P or VIP. Nerve fibres containing noradrenaline were the most numerous, while fibres containing substance P were observed least frequently in both types of vessel. For each putative neurotransmitter, the density of the innervation of the cerebral veins was less than that of cerebral arteries.2. The vasomotor responses of individual pial arteries and veins on the convexity of the cerebral cortex to perivascular micro-injection of noradrenaline, substance P and VIP were examined in twenty-five cats anaesthetized with alpha-chloralose.3. The perivascular micro-application of noradrenaline resulted in pronounced dose-dependent reductions in the diameter of pial veins (maximum calibre reduction: 32+/-3% noradrenaline 10(-5) M) and arteries (22+/-3% noradrenaline 10(-5) M). Pial veins were more sensitive to noradrenaline than were pial arteries tested under similar conditions. The reductions in the diameter of cerebral veins and arteries resulting from the administration of noradrenaline could be attenuated by the concomitant micro-application of phentolamine (10(-6) M).4. The perivascular micro-application of substance P effected significant dose-dependent increases in the calibre of pial veins (maximum calibre increase: 16+/-4% substance P 10(-7) M) which were of a similar magnitude to those observed in pial arteries in response to this peptide (21+/-4% substance P 10(-6) M).5. The perivascular micro-application of VIP resulted in small increases in the calibre of pial veins (maximum calibre increase: 9+/-2% VIP 10(-8) M) which were proportionately smaller than those observed in pial arteries in response to this peptide (23+/-5% VIP 10(-7) M).

Animals↗
PubMed1982

Local cerebral circulatory and metabolic effects of indomethacin.

The effects of indomethacin, a prostaglandin synthesis inhibitor, upon local cerebral glucose utilization and local cerebral blood flow have been examined in 36 conscious, lightly restrained rats. Cerebral glucose utilization and cerebral blood flow were determined by means of the quantitative autoradiographic techniques that utilize, respectively, 2-deoxy-D-[1-14C]glucose and iodo[14C]antipyrine as tracer molecules. The administration of indomethacin (0.3-30 mg/kg iv) did not alter significantly the rate of glucose utilization in any of the 38 discrete regions of the central nervous system that were examined. In contrast, cerebral blood flow in every region was significantly reduced by between 30 and 50% from vehicle-injected control levels after the administration of 10 mg/kg iv indomethacin and by 5-31% after 1 mg/kg iv indomethacin. These results provide further evidence that prostaglandins may play a major role in cerebrovascular regulation, but they provide no positive evidence for a role in neuronal activity, as reflected in local cerebral glucose utilization.

Animals↗
PubMed1982

Alterations in local cerebral glucose utilization during hemorrhagic hypotension in the rat.

The alterations in local cerebral glucose utilization in 58 anatomically discrete regions which occur during a period of hemorrhagic hypotension have been investigated in conscious rats, using the quantitative autoradiographic 14C-deoxyglucose technique. Hemorrhagic hypotension (mean arterial pressure reduced by approximately 50 mm Hg) effected significant increases in glucose utilization in eight areas of the central nervous system, namely, the nucleus of the tractus solitarius (glucose utilization increased by 38%), the dorsal motor nucleus of the vagus (by 36%), locus coeruleus (by 38%), lateral habenular nucleus (by 40%), periventricular nucleus of the hypothalamus (by 41%), paraventricular nucleus of the hypothalamus (by 97%), supraoptic nucleus (by 86%), and the interstitial nucleus of the stria terminalis (by 84%). In five of these eight areas (nucleus of the tractus solitarius, dorsal motor nucleus of the vagus, paraventricular and supraoptic nuclei, and the interstitial nucleus of the stria terminalis), a significant relationship could be demonstrated between the level of glucose utilization and mean arterial blood pressure. In the majority of the CNS regions examined (neocortex, hippocampus, thalamus, extrapyramidal and motor areas), hemorrhagic hypotension was without significant effect upon local cerebral glucose utilization. The results provide direct evidence of the functional involvement of specific brain areas of conscious rats (thus obviating complicating anesthetic influences) in the response of the CNS to hemorrhagic hypotension.

Animals↗
PubMed1982

Cerebrovascular permeability following MCA occlusion in the rat. The effect of halothane-induced hypotension.

A quantitative autoradiographic technique that utilizes carbon-14-aminoisobutyric acid (14C-AIB) as a tracer was used to study alterations in cerebral microvascular permeability in 15 rats. Five were "sham-operated" controls and 10 underwent microsurgical, unilateral occlusion of the proximal middle cerebral artery (MCA). Histological changes indicative of focal cerebral ischemia were observed in only the latter 10 animals. These changes were confined to tissue normally perfused by the occluded MCA. After MCA occlusion, five animals were also subjected to transient halothane-induced hypotension (mean arterial blood pressure 50 mm Hg) for 20 to 30 minutes. Only in these five animals were blood-to-brain transfer constants (ki) significantly increased (by approximately 100%) at 4 hours after MCA occlusion. The topographical distribution of this alteration in cerebral microvascular permeability corresponded closely with the histological changes. Neither proximal MCA occlusion nor halothane-induced hypotension alone was associated with any focal or diffuse increase in ki after 4 hours.

Aminoisobutyric Acids↗
PubMed1982

Autoradiographic assessment of choroid plexus blood flow and glucose utilization in the unanesthetized rat.

Choroid plexus blood flow (CPBF) and glucose utilization (CPGU) were measured in two groups, each of seven identically prepared, unanesthetized rats, using complementary quantitative autoradiographic techniques. Both CPBF and CPGU were lowest in the lateral ventricles (0.83 +/- 0.01 . g-1 . min-1 and 0.70 +/- 0.02 mumoles . g-1 . min-1, respectively) and highest in the fourth ventricle (1.56 +/- 0.05 ml l g-1 . min-1 and 1.39 +/- 0.05 mumoles . g-1 . min-1, respectively). Despite this heterogeneity, the proportionate relationship between CPBF and CPGU was relatively constant throughout the ventricular system. This suggests that blood flow and metabolism may normally be coupled in the choroid plexus, and that the choroid plexus of the fourth ventricle may account for a disproportionate share of the functional activity of this tissue.

Absorptiometry, Photon↗
PubMed1981

The effects of chloral hydrate anesthesia on the metabolic response in the substantia nigra to apomorphine.

The effects of apomorphine (1 mg/kg) upon glucose utilization in the substantia nigra (pars compacta) have been examined with 2-deoxyglucose autoradiography in conscious rats and rats anesthetized with chloral hydrate. In conscious rats, apomorphine increased glucose use by 23%, whereas in the anesthetized rats, apomorphine decreased glucose use by 24%. These divergent responses to apomorphine highlight the difficulties associated with the use of chloral hydrate anesthesia in the study of nigro-striatal systems.

Animals↗
PubMed1981

Heterogeneous depression of glucose utilization in the caudate nucleus by GABA agonists.

Local cerebral glucose utilization in the rat caudate nucleus has been examined following the intravenous administration of the GABA agonists muscimol and THIP. Although glucose utilization was reduced throughout the striatum following GABA agonists, the magnitude of the reductions in the lateral portion of the nucleus were markedly greater than in other portions of the caudate nucleus. This medial--lateral heterogeneity in response to GABA agonists contrasts with the known rostral--caudal heterogeneity in the distribution of biochemical markers for GABA.

Animals↗
PubMed1981

Alterations in local cerebral glucose utilisation in specific thalamic nuclei following apomorphine.

The alterations in local cerebral glucose utilisation in eight discrete nuclei in the thalamus following the administration of apomorphine (0.5 mg kg-1) have been investigated with the autoradiographic 2-deoxyglucose technique in 11 conscious rats. In two thalamic nuclei (parafascicular and ventrolateral nuclei), glucose utilisation was significantly elevated following apomorphine; in two thalamic nuclei (the anterior medial and anterior ventral nuclei), glucose utilisation was significantly reduced following apomorphine; and in four nuclei (lateral geniculate, medial geniculate, mediodorsal, and lateral thalamic nuclei), glucose use was unchanged.

Animals↗
PubMed1981

Effects of pentobarbital on contractile responses of feline cerebral arteries.

The effects of pentobarbital on the contractile responses of isolated feline middle cerebral arteries have been examined. In the presence of pentobarbital (3 x 10(-4)M), the maximum contractions effected by potassium, noradrenaline, and prostaglandin F2 alpha were reduced by 37 +/- 3, 69 +/- 3, and 10 +/- 6%, respectively. The results caution against the use of pentobarbital as an anaesthetic agent in investigations of cerebrovascular reactivity.

Animals↗
PubMed1981

Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion.

A procedure for occluding the stem of the proximal middle cerebral artery of the rat is described. The operation is performed under anaesthesia through a small subtemporal craniectomy. After occlusion, 3 animals were perfused with carbon block and 8 with a FAM fixative (40% formaldehyde, glacial acetic acid, and methanol). The findings were compared with sham-operated animals. Carbon black studies demonstrated an area of impaired perfusion corresponding to the territory of the occluded artery in each animal. Neuropathological studies invariably showed that there was ischaemic brain damage in the cortex and basal ganglia. The frontal cortex was involved in every animal, as was the lateral part of the neostriatum; the sensorimotor and auditory cortex were involved in most animals, whereas the occipital cortex and medial striatum were involved only infrequently. The damage produced by ischaemia could be readily distinguished from the small local lesion seen at the surgical site in sham-operated animals. The ability to produce a consistent focal ischaemic lesion in the rodent brain provides a technical approach that is sufficiently reproducible to enable investigation of the pathophysiology of ischaemia using recently developed autoradiographic and neurochemical methods.

Animals↗
PubMed1981

Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by [14C]iodoantipyrine autoradiography following middle cerebral artery occlusion.

Local cerebral blood flow has been measured by quantitative autoradiography, employing [14C]iodoantipyrine as tracer, in rats killed half an hour after occlusion of the middle cerebral artery. The results were compared with pattern of local cerebral blood flow (CBF) in sham-operated rats and with neuropathological findings. In every animal there was a profound reduction (to 13% of control levels)in blood flow in the neocortex previously by the occluded artery. The level of blood flow in the areas in which ischaemic brain damage occurred was 0.24 +/- 0.03 ml g-1 min-1 (mean +/- SEM). this level of CBF is considerably greater than that reported following a similar surgical procedure in cats and primates. Moderate reductions in blood flow were also seen outside the territory of the occluded artery and in parts of the opposite hemisphere. Absolute increases in blood flow (hyperaemia) were seen only in the substantia nigra and globus pallidus ipsilateral to the occlusion. It is of the middle cerebral artery are reflections of alterations in neuronal function and metabolic activity secondary to the ischaemic lesion.

Animals↗
PubMed1981

Substance P: immunohistochemical localization and effect upon cat pial arteries in vitro and in situ.

1. Nerve fibres containing substance P immunoreactivity were present in the adventitia and the adventitia-media border of all cat cerebral arteries which were examined. Substance P immunoreactivity was most abundant in cerebral arteries from the rostral portion of the circle of Willis. 2. Substance P effected a dose-dependent relaxation of feline middle cerebral arteries which had been contracted with prostaglandin F2 alpha. The maximum relaxation (16 +/- 0.3 mN) was achieved with substance P at a concentration of 10-6 M. 3. In cats anaesthetized with alpha-chloralose, the perivascular microinjection of substance P effected dose-dependent increases in arteriolar calibre. The maximum increase in calibre (19 +/- 3%) was observed following the injection of 10(-6) M-substance P.

Animals↗