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Biomedical subjects

J McCulloch

Publications and source records attributed to J McCulloch.

At least 217 records · Page 12Linked to original sources
PubMed1983

The effects of dexamethasone administration and withdrawal on water permeability across the blood-brain barrier.

We examined the effects of dexamethasone administration and withdrawal on regional cerebral blood flow (CBF) and the permeability surface area (PS) product for water in the central nervous system of conscious rats. There were no significant changes in CBF. Dexamethasone treatment produced a significant decrease in the PS product for water in the cerebral cortex, while withdrawal of dexamethasone resulted in a significant increase. Water content of the cerebral cortex was also increased in rats from which dexamethasone had been withdrawn. These findings may help in understanding the pathogenesis of brain swelling in some patients.

Animals↗
PubMed1983

Functional role for vasoactive intestinal polypeptide in the caudate nucleus: a 2-deoxy[14C]glucose investigation.

The quantitative autoradiographic 2-deoxy-[14C]glucose technique has been used with conscious rats to investigate the functional consequences (reflected as alterations in local rates of glucose utilization) of unilateral intrastriatal administration of vasoactive intestinal polypeptide. Intrastriatal administration of vasoactive intestinal polypeptide (20 pmol) significantly increased local glucose utilization in the injected striatum, where the increased use was localized in small punctate areas (100-500 microns wide in coronal sections) scattered throughout the nucleus at considerable distances (up to 4 mm) from the injection site. Significantly increased glucose utilization after intrastriatal injection of vasoactive intestinal polypeptide was observed in a number of regions (e.g., substantia nigra pars compacta, entopeduncular nucleus, lateral habenular nucleus, entorhinal, pyriform cortices, and amygdala) with known primary or secondary neuronal connections with the caudate nucleus. These alterations in glucose utilization were highly focal in nature, with the majority (40 of the 50 examined) of brain regions displaying unaltered rates of glucose utilization. The data provide evidence, obtained in conscious animals, that vasoactive intestinal polypeptide can modify functional processes in the caudate nucleus.

Animals↗
PubMed1983

The effects of apomorphine upon local cerebral glucose utilization in conscious rats and in rats anesthetized with chloral hydrate.

The effects of the dopaminergic agonist apomorphine (1 mg . kg-1 i.v.) upon local cerebral glucose utilization in 43 anatomically discrete regions of the CNS were examined in conscious, lightly restrained rats and in rats anesthetized with chloral hydrate by means of the quantitative autoradiographic [14C]2-deoxyglucose technique. In animals anesthetized with chloral hydrate, glucose utilization was reduced throughout all regions of the CNS from the levels observed in conscious animals, although the magnitude of the reductions in glucose use displayed considerable regional heterogeneity. With chloral hydrate anesthesia, the proportionately most marked reductions in glucose use (by 40-60% from conscious levels) were noted in primary auditory nuclei, thalmaic relay nuclei, and neocortex, and the least pronounced reductions in glucose use (by 15-25% from conscious levels) were observed in limbic areas, some motor relay nuclei, and white matter. In conscious, lightly restrained rats, the administration of apomorphine (1 mg . kg-1) effected significant increased in glucose utilization in 15 regions of the CNS (e.g., subthalamic nucleus, ventral thalamic nucleus, rostral neocortex, substantia nigra, pars reticulata), and significant reductions in glucose utilization in two regions of the CNS (lateral habenular nucleus and anterior cingulate cortex). In rats anesthetized with chloral hydrate, the effects of apomorphine upon local glucose utilization were less widespread and less marked than in conscious animals. In only two of the regions (the globus pallidus and septal nucleus), which displayed increased glucose use following apomorphine in conscious rats, were significant increases in local glucose utilization observed with this agent in chloral hydrate-anesthetized rats. In the pars compacta of the substantia nigra, in which apomorphine increased glucose utilization in conscious animals, significant reductions in glucose utilization were observed following apomorphine in rats anesthetized with chloral hydrate. The profound effects of chloral hydrate anesthesia upon local cerebral glucose use, and the modification by this anesthetic regime of the local metabolic responses to apomorphine, emphasize the difficulties which exists in the extrapolation of data from anesthetized animals to the conditions which prevail in the conscious animal.

Animals↗
PubMed1983

Hormonal influence on water permeability across the blood-brain barrier.

We have shown that steroid manipulations may influence the rate of flux of water across the blood-brain barrier. Such changes are regionally variable and are best seen in the cerebral cortex. Administration of dexamethasone produced decreased water permeability while withdrawal of dexamethasone and ethinyloestradiol resulted in increased permeability. Increased water content in cerebral cortex was demonstrated after steroid withdrawal and ethinyloestradiol administration. We believe that these experimental findings may have relevance in the clinical situation and may help in understanding the pathogenesis of some types of brain oedema. One such example is benign intracranial hypertension where brain swelling is seen typically in young obese females and is also associated with the contraceptive pill, pregnancy and corticosteroid withdrawal.

Animals↗
PubMed1982

The distribution of alterations in energy metabolism in the rat brain produced by apomorphine.

The effects of the putative dopaminergic agonist, apomorphine (0.15-5 mg/kg, i.v.), on glucose utilization in 43 anatomically discrete regions of the rat brain have been examined by the quantitative autoradiographic 2-deoxyglucose technique. Apomorphine failed to alter the rates of glucose utilization in 25 of these regions (for example, primary auditory areas, regions of white matter, hippocampal areas, nucleus accumbens and caudal regions of the neocortex). Dose-dependent alterations in glucose utilization were observed following apomorphine administration in a number of regions known to contain dopaminergic receptors (viz: caudate nucleus, substantia nigra, amygdala, subthalamic nucleus and anterior cingulate cortex). Moreover, dose-dependent alterations in glucose utilization were produced by apomorphine in a number of regions thought to contain few specific dopaminergic receptors (e.g., cerebellar hemisphere and vermis, lamina VI of rostral neocortical areas, and ventral nucleus of the thalamus). The distribution of alterations in glucose utilization following apomorphine administration are considered to reflect the functional involvement of the region in the overall response to apomorphine, and not simply the topography of dopaminergic receptor mechanisms.

Animals↗
PubMed1982

Distribution of effects of haloperidol on energy metabolism in the rat brain.

The effects of the putative dopaminergic antagonist, haloperidol (0.01-10 mg/kg, i.v.), on cerebral glucose utilization in 43 anatomically discrete regions of the rat brain have been examined by the quantitative autoradiographic 2-deoxyglucose technique. Dose-dependent reductions in glucose utilization were observed in 10 regions of the CNS (e.g. hippocampus, ventral thalamus and almost the entire neocortex, with the notable exception of anterior cingulate cortex). Two regions of the CNS (nucleus accumbens and pars compacta of the substantia nigra) displayed dose-related increases in glucose utilization following haloperidol administration. In addition to these specific alterations, the largest doses of haloperidol produced widespread, moderate (about 25%) reductions in glucose utilization throughout the CNS. The prior administration of haloperidol (0.1 mg/kg) prevented the effects on glucose utilization of the administration of apomorphine (1.5 mg/kg) in all regions of the CNS examined. The distribution of alterations in glucose utilization following haloperidol administration are considered in relation to the overall functional consequences of dopaminergic receptor blockade.

Animals↗
PubMed1982

Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of Bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association.

The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (P greater than 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

Adult↗
PubMed1982

Alterations in local cerebral glucose utilization during chronic treatment with an ACTH 4-9 analog.

Adrenocorticotrophic hormone (ACTH) and structural analogs of the fragment ACTH4-9 have marked effects upon behavior (particularly in relation to memory processes). The effects of the chronic (10 day) administration of the potent analog (Met(O2)4,D-Lys8,Phe9]ACTH4-9(100 microgram/kg per day i.p,) upon local cerebral glucose utilization have been examined using the autoradiographic 2-deoxyglucose technique in the attempt to identify the neuroanatomical sites involved functionally in the central actions of this ACTH4-9 analog. Of the 49 anatomically discrete regions examined, significant increases in glucose utilization were observed only in the hippocampus (stratum molecular lacunosum lacunosum and parasubiculum, increased by 16 and 17% respectively), the anterior nucleus of the thalamus (by 23%) and anterior cingulate cortex (by 30%). The highly localized alterations in glucose utilization which were observed following treatment with this ACTH4-9 analog provide evidence for the functional involvement of a hippocampal-anterior-thalamic-anterior cingulate cortical circuit in the actions of this peptide fragment.

Adrenocorticotropic Hormone↗
PubMed1982

Th central noradrenergic system in the rat: metabolic mapping with alpha-adrenergic blocking agents.

Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose technique in 73 normal, awake rats treated with different doses of the alpha-adrenergic blockers, phenoxybenzamine, phentolamine and yohimbine. Three types of responses were elicited by the administration of these drugs. The predominant effect observed after administration of all alpha-blockers was a widespread depression of glucose utilization, particularly within the neocortex. The effect was most pronounced with phenoxybenzamine. In a few structures (locus coeruleus, interstitial nucleus of the stria terminalis, medial forebrain bundle, periventricular nucleus and some medullary and hypothalamic nuclei associated with the regulation of blood pressure) marked increases in glucose utilization were observed. Administration of phentolamine resulted in increased glucose utilization in all the central components of the auditory system (cochlear n., superior olivary n., n. lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). Phenoxybenzamine and yohimbine tended to decrease glucose utilization in the auditory system. Alternating columns with higher and lower rates of local glucose consumption were observed in most of the neocortical areas and in the cerebellar vermis. The significance of these columns is not clear.

Adrenergic alpha-Antagonists↗
PubMed1982

Influence of alpha-receptor blocking agents upon metabolic activity in nuclei involved in central control of blood pressure.

The energy metabolism of the central nervous structures involved in the regulation of blood pressure was examined by means of the autoradiographic 2-deoxy-D-[14C]glucose method in normal, awake rats during hypotension induced by the alpha-adrenergic blockers, phentolamine, phenoxybenzamine, and yohimbine. Administration of these alpha-blockers produced a dose-dependent increase of glucose consumption in the medial nucleus of the solitary tract (NTSm), the dorsal motor nucleus of the vagus (DMX), the nucleus ambiguus (NA), and the paraventricular (PAVH) and supraoptic (SO) hypothalamic nuclei. However, in the external cuneate nucleus and in the paramedian reticular nucleus there was a decrease in glucose utilization. These changes appear to be at least partly due to the hypotension produced by the drugs in addition to their central effects; when the hypotension was prevented by administration of the plasma expander, dextran, in phenoxybenzamine-treated rats, the effects were less than those observed in animals with hypotension not limited by dextran infusion.

Adrenergic alpha-Antagonists↗
PubMed1982

Specific alterations in local cerebral glucose utilization following striatal lesions.

Regional cerebral glucose utilization was measured in conscious, lightly restrained rats, using the 2-deoxyglucose autoradiographic technique, 10 days after the unilateral injection of kainic acid into the striatum. The stereotactic infusion of kainic acid (2 mug in 2 mul of mock CSF) resulted in lesions localized to the caudate nucleus with no involvement of surrounding brain areas, such as septal nucleus and nucleus accumbens. Only mechanical damage around the needle tract was observed in CSF injected control animals. Local cerebral glucose use was most markedly affected ipsilateral to the infusion site in areas which normally receive input from the caudate nucleus. In globus pallidus and substantia nigra pars reticulata, increases in glucose use of 82% and 74%, respectively, were measured when compared with CSF injected controls. However, significant increases were also measured in contralateral pallidus and substantia nigra reticulata (16% and 20%, respectively). Of the brain structures examined, significant unilateral increases from control were observed in ipsilateral habenula (23%) and ventrolateral thalamus (13%), and contralateral substantia nigra pars compacta (14%) and sensory-motor cortex (15%). However, the side-to-side difference in response from control was not large. Symmetrical, bilateral increases in glucose use were found in the nucleus accumbens (15%), ventral tegmental area (24%), and red nucleus (17%). The only area in which the measured rate of glucose use was decreased was the ipsilateral caudate nucleus. However, these changes were invariably associated with histologically definable tissue damage. Caution must therefore be exercised in the interpretation of this result and that from other areas where damage was apparent. The increases of functional activity, as measured by glucose utilization within certain regions in the absence of cellular damage, provide an insight into the mechanisms by which overt motor behavior returns to normal a short time after the removal of striatal interneurons and efferent perikarya by the neurotoxic action of kainic acid. Of particular interest are the responses observed contralateral to the affected striato-nigral system in view of the proposed functional interaction between the two sides of the brain in the absence of direct neuronal pathways.

Animals↗
PubMed1982

Comparison of the effects of potassium and pH on the calibre of cerebral veins and arteries.

The vasomotor response of individual pial veins and arteries on the convexity of the cerebral cortex to perivascular microinjection of mock cerebrospinal fluid (CSF) containing various concentrations of potassium (K+) and of various pH (achieved by altering the bicarbonate, HCO-3 concentration) have been examined in cats anaesthetised with alpha-chloralose. Microapplication of CSF containing 0 mM HCO-3 (pH 4.80) effected significant increases in calibre of pial veins and arteries of 9.3 +/- 2.4% and 38.2 +/- 4% respectively (mean calibre change +/- SE), whereas CSF containing 22 mM HCO-3 (pH 7.45) which constricted pial arteries significantly (-18.5 +/- 2.9%) minimally altered venous calibre (-4.3 +/- 2.2%). Microapplication of CSF containing 0 mM potassium resulted in a significant reduction in pial arterial calibre (-11.4 +/- 2.8%) but failed to alter pial venous calibre (-0.3 +/- 0.6%). Perivascular microapplication of CSF containing moderately elevated potassium concentrations (10 mM) which effected marked, significant increases in pial arterial calibre (49.3 +/- 3.9%) did not significantly alter the calibre of the pial veins (mean response -1.6 +/- 2.4%). The perivascular administration of CSF containing a high concentration of potassium (40 mM) resulted in the significant constriction of both pial veins (-13.5 +/- 0.9%) and pial arteries (-47.2 +/-6.3%). The magnitude of the response was significantly smaller in the pial veins. The relative insensitivity to K+ and pH of the pial veins as compared to pial arteries suggests that alteration in the chemical composition of of the perivascular fluid are of lesser importance in the control of cerebrovascular capacitance than for the regulation of cerebrovascular resistance.

Animals↗