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Biomedical subjects

D G Nehls

Publications and source records attributed to D G Nehls.

At least 19 recordsLinked to original sources
PubMed1990

The effects of N-methyl-D-aspartate receptor blockade with MK-801 upon the relationship between cerebral blood flow and glucose utilisation.

The local cerebral circulatory and metabolic effects of MK-801, a selective non-competitive N-methyl-D-aspartate receptor antagonist have been examined in conscious rats with quantitative autoradiographic techniques using [14C]iodoantipyrine and [14C]2-deoxyglucose as tracers. Local cerebral blood flow (CBF) and local cerebral glucose utilisation (GU) were measured in 41 discrete neuroanatomical loci using identical criteria for region of interest localisation. Animals received either saline or MK-801 (0.5 mg/kg in saline) intravenously 10 min prior to the start of GU determination, or 15 min before the CBF measurement. MK-801 effects an immediate transient, elevation in mean arterial pressure (elevated by 30% from baseline) which returned rapidly to preinjection levels and a sustained moderate hypercapnia (arterial carbon dioxide tension increased by 16%) which persisted throughout the measurement periods. Statistically significant changes in GU were observed in 13 brain region structures after MK-801 administration. Glucose utilisation was significantly and markedly elevated with MK-801 in some limbic structures (particularly the hippocampus, posterior cingulate and entorhinal cortices), the inferior colliculus and most of the neocortex displayed moderate reductions in GU after MK-801 treatment. In the majority of brain regions (28 or the 41 studied), MK-801 minimally altered GU. There were widespread alterations in local CBF with MK-801 although in the majority of brain regions (24 of the 41 studied) there was no statistically significant alteration in CBF with MK-801. With one exception (the anterior thalamic nucleus), CBF was increased with MK-801 in all regions in which glucose use was elevated with the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Experimental intracerebral hemorrhage: early removal of a spontaneous mass lesion improves late outcome.

The purpose of the present study was to determine whether early removal of an experimental intracerebral mass altered cerebral blood flow, brain water content, neuropathological findings, or neurological function 24 hours later. In three experimental series, a 50-microliter balloon was inflated within the right caudate nucleus in rats. At 24 hours after inflation, we studied cerebral blood flow by quantitative autoradiography, brain specific gravity, and qualitative histopathology by light microscopy. The animals were also assessed using a simple neurological deficit scale. In each series, half of the animals had the balloon inflated for 10 minutes (Group 1), and half had the balloon inflated permanently (Group 2). After transient inflation, there were surprisingly small differences in the blood flow between the two cerebral hemispheres at 24 hours. By contrast, in animals with permanent inflation, several indices of blood flow were significantly worse in the hemisphere ipsilateral to the balloon: the mean and median blood flow levels in the caudate nucleus; the mean blood flow in the cerebral cortex; and the area of cortex with ischemic levels of blood flow. The specific gravity was reduced in areas surrounding the site of balloon insertion after either transient or permanent inflation, and there was evidence of ischemic cell damage in all animals studied. These changes were more severe after permanent inflation, but the differences were not significant. Neurological outcome was significantly better after transient as compared with permanent inflation. The present findings contradict previous results and suggest that early removal of an intracerebral mass may have subsequent benefits.

Animals↗
PubMed1989

Effects of NMDA antagonists, MK-801 and CPP, upon local cerebral glucose use.

The effects upon cerebral glucose utilisation of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801, a non-competitive N-methyl-D-aspartate (NMDA, receptor antagonist) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, a competitive NMDA receptor antagonist) were examined in conscious, lightly restrained rats. Cerebral glucose utilisation was assessed quantitatively in 74 brain regions with [14C]2-deoxyglucose autoradiography. The intravenous (i.v.) administration of MK-801 (0.05-5 mg/kg) induced heterogeneous patterns of altered cerebral glucose utilisation with statistically significant increases being observed in 21 brain areas and statistically significant decrease in 8 brain regions. Pronounced dose-related increases in glucose use were observed after MK-801 in the subicular complex, hippocampus molecular layer, dentate gyrus, limbic system (posterior cingulate cortex; mamillary body; anteroventral thalamic nucleus), olfactory areas and substantia nigra (pars reticulata). Glucose use in the neocortex and inferior colliculus was particularly sensitive to reduction by MK-801 administration. The pattern of altered glucose use after administration of CPP (3-30 mg/kg, i.v.) differed markedly from that observed after MK-801 treatment. Statistically significant increases in glucose use after CPP were noted in 11 brain areas and statistically significant decreases in 5 of the regions examined. Regions in which increases were noted after CPP included hippocampus molecular layer, olfactory areas, cochlear nucleus, vestibular nucleus, cerebellar nucleus, superior olives and substantia nigra (pars reticulata). These data indicate that widespread, anatomically organised alterations in cerebral function are associated with the administration of NMDA receptor antagonists despite the minor role normally ascribed to these receptors in conventional fast synaptic transmission. The distinct patterns of response to competitive and non-competitive antagonists may be a reflection of the differential responses of the two modes of receptor blockade to increased glutaminergic transmission.

Animals↗
PubMed1989

Effect of the NMDA antagonist MK-801 on local cerebral blood flow in focal cerebral ischaemia in the rat.

The effects of MK-801 upon local CBF after permanent middle cerebral artery (MCA) occlusion have been examined using [14C]iodoantipyrine autoradiography in halothane-anaesthetised rats. MK-801 (0.5 mg kg-1 i.v.) or saline was administered 30 min before MCA occlusion and CBF measured approximately 40 min after occlusion. In the hemisphere contralateral to the occluded MCA, MK-801 significantly reduced local CBF in 19 of the 22 regions examined from the levels in saline-treated rats. In the contralateral hemisphere, after treatment with MK-801, blood flow was reduced by an average of 37% with little variation in the magnitude of the reductions in different regions. In the hemisphere ipsilateral to MCA occlusion, MK-801 reduced CBF in almost every region located outside the territory of the occluded MCA. Within the territory of the occluded MCA, blood flow in the MK-801-treated rat did not significantly differ from values in vehicle-treated rats in any of the five cortical areas examined, although in the caudate nucleus there was a tendency for CBF to be lower in rats pretreated with MK-801. MK-801 had no effect on the amount of hypoperfused cerebral tissue (CBF less than 30 ml 100 g-1 min-1) in the ipsilateral hemisphere at any coronal plane examined; e.g., at coronal plane anterior 7.2 mm, 51 +/- 5% of the hemisphere displayed CBF of less than 30 ml 100 g-1 min-1 in saline-treated rats with MCA occlusion compared with 52 +/- 8% of the hemisphere in rats treated with MK-801 prior to MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Differential effects of competitive and non-competitive N-methyl-D-aspartate antagonists on glucose use in the limbic system.

The effects on cerebral glucose utilisation of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801, a non-competitive NMDA receptor antagonist) have been examined in conscious rats. Cerebral glucose utilisation was assessed quantitatively with 14C-2-deoxyglucose autoradiography. MK-801 (0.05-5 mg/kg, i.v.) markedly increased glucose use in a number of limbic brain areas such as the mamillary body, anterior thalamic nucleus, posterior cingulate cortex and hippocampus. CPP (3-30 mg/kg, i.v.), in contrast, effected minimal alterations in glucose use in the limbic system. The functional consequences in vivo, as reflected in local cerebral glucose use, of competitive blockade of the NMDA receptor differ markedly from blockade with non-competitive antagonists.

Animals↗
PubMed1988

The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat.

Excessive activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor has been implicated in the sequence of neurochemical events that results in irreversible neuronal damage in cerebral ischemia. The effects of the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) upon the amount of ischemic brain damage has been assessed quantitatively in the lightly anesthetized rat. Focal cerebral ischemia was produced by the permanent occlusion of one middle cerebral artery (MCA), and the animals were killed 3 hours after the arterial occlusion. MK-801 (0.5 mg/kg) was administered intravenously either 30 minutes prior to MCA occlusion or 30 minutes after the induction of ischemia. Pretreatment with MK-801 reduced the volume of ischemic damage both in the cerebral cortex (by 38% compared with untreated rats with MCA occlusion; p less than 0.01) and in the caudate nucleus (by 18% compared with controls; p less than 0.05). Treatment with MK-801, initiated 30 minutes after MCA occlusion, reduced the volume of ischemic damage in the cerebral cortex (by 52% compared with controls; p less than 0.01). The volume of ischemic damage in the caudate nucleus was minimally influenced by MK-801 treatment initiated after MCA occlusion. The antiischemic effects of MK-801 were readily demonstrable despite the hypotension that MK-801 induced in rats anesthetized with halothane (0.5%), nitrous oxide (70%), and oxygen (30%). The potency of MK-801 in reducing ischemic brain damage, even when administered after the induction of ischemia, highlights the potential use of NMDA receptor antagonists for the treatment of focal cerebral ischemia in humans.

Animals↗
PubMed1988

Focal cerebral ischaemia in the cat: treatment with the glutamate antagonist MK-801 after induction of ischaemia.

The effects of the glutamate N-methyl-D-aspartate receptor antagonist MK-801 in reducing ischaemic brain damage have been examined in anaesthetised cats, with drug treatment being initiated 2 h after the induction of cerebral ischaemia. Focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischaemic damage was assessed at 16 predetermined stereotactic planes. Treatment with MK-801 (5 mg/kg, i.v.) 2 h after middle cerebral artery occlusion reduced significantly the volume of ischaemic damage (from 1,625 +/- 384 mm3 of the cerebral hemisphere in vehicle-treated cats to 792 +/- 385 mm3 in MK-801-treated cats). The demonstration of reduced ischaemic brain damage with MK-801, when the agent is administered after the induction of ischaemia, extends the therapeutic potential of such agents in the treatment of focal cerebral ischaemia in humans.

Animals↗
PubMed1988

Experimental intracerebral hemorrhage: progression of hemodynamic changes after production of a spontaneous mass lesion.

The aim of the study was to determine whether the extent of ischemia produced by an experimental space-occupying lesion changed between 5 minutes and 4 hours after the production of a lesion. In two groups of rats, a 50-microliter balloon was inflated in the right caudate nucleus. Cerebral blood flow (CBF) was determined by 14C-iodoantipyrine quantitative autoradiography, in Group 1 (n = 6) 5 minutes after inflation and in Group 2 (n = 6) 4 hours later. After 5 minutes of inflation, the mean blood flow in the caudate nucleus was reduced to 65% of the contralateral value and 11.5% of the ipsilateral caudate nucleus had a blood flow of below 25 ml/100 g/minute. After 4 hours of inflation, there was a greater fall in the mean CBF of the ipsilateral caudate nucleus to 30% of the contralateral value, and 38.9% of the ipsilateral caudate nucleus had a CBF of less than 25 ml/100 g/minute. The differences between the two groups were significant (mean CBF, P less than 0.01; CBF less than 25 ml/100 g/minute, P less than 0.02). The results show that the initial ischemic lesion produced by a spontaneous intracerebral space-occupying lesion does not remain static, but progresses with time and is significantly greater after 4 hours than after 5 minutes. Interventions that reduce the progression of ischemia may be beneficial in reducing the ultimate amount of ischemic brain damage.

Animals↗
PubMed1987

A comparison of the cerebral protective effects of isoflurane and barbiturates during temporary focal ischemia in primates.

Isoflurane has protective properties during experimental global brain ischemia or hypoxia. However, this has not been evaluated in the more common case of focal ischemia, e.g., as caused by middle cerebral artery occlusion (MCAO). The authors therefore compared the effects of isoflurane, thiopental, and N2O/fentanyl anesthesia on neurologic and neuropathologic outcome in baboons subjected to 6 h of transorbital left MCAO. Prior to MCAO, animals were assigned to one of three groups: Group 1 (n = 7) received isoflurane (in O2/air) in concentrations sufficient to maintain deep burst suppression on the EEG (2.0% +/- 0.5% inspired, mean +/- SD); group 2 (n = 6) received thiopental (O2/air) in doses adequate to maintain similar EEG suppression (3.6 +/- 0.7 g total); and group 3 (n = 6) received 60% N2O/40% O2 and fentanyl (25 micrograms/kg load, 3 micrograms X kg-1 X h-1 infusion). Efforts were made to keep mean arterial pressure (MABP) between approximately 80 and 100 mmHg, using nitroprusside/hydralazine or phenylephrine/metaraminol, with PaCO2 at approximately 30 mmHg. The selected anesthetic was established 45 min before MCAO, was maintained until 1 h after clip removal, and in decreasing concentrations for 5 h. Neurologic status was scored for 7 days and formalin-fixed brains were later sectioned for determination of infarction volume. Six of seven group 1 (isoflurane) animals were hemiplegic, and 7/7 had verified infarctions. By contrast, 4 of 6 group 2 (thiopental) animals were normal, with 2/6 having infarctions. Outcome in group 3 (N2O/fentanyl) was intermediate between groups 1 and 2 (3/6 hemiplegic, 4/6 with infarctions). Differences in the infarction rates between groups 1 and 2 was significant (P less than 0.05), while a similar comparison of neurologic outcome scores achieved a P value of 0.055. Infarctions in group 1 were more hemorrhagic in character than in group 3 (groups 1 and 2 could not be meaningfully compared). These results must be considered in light of differences in MABP during the occlusion period; MABP in group 1 was approximately 80 mm Hg in spite of vasopressor use, while that in group 2 was approximately 100 mmHg (in spite of vasodilators). Nevertheless, they fail to demonstrate any protective value of isoflurane anesthesia, at least when compared with thiopental.

Anesthesia, Inhalation↗
PubMed1985

Synovial cyst of a cervical facet joint: case report.

Intraspinal synovial cysts are rare. Those reported have occurred in the lumbar region. We report a case of an extradural true synovial cyst of the cervical spine causing spastic paraparesis. The cyst occurred after a cervical spine fracture and, hence, was probably related to trauma. Surgical therapy resulted in a satisfactory recovery.

Adult↗
PubMed1985

Multiple unusual aneurysms and arteriovenous malformation in a single patient: a case report.

A patient with multiple unusual aneurysms and an arteriovenous malformation (AVM) is presented. Aneurysms involving the meningohypophyseal trunk and the feeding vessel of the AVM were observed. Two additional aneurysms assumed a pantaloon appearance. The largest aneurysm was responsible for the patient's subarachnoid hemorrhage. This aneurysm and two adjacent aneurysms were clipped successfully, and the patient made an uneventful recovery. Subsequent angiography revealed a stable appearance of the remaining aneurysms and AVM.

Cerebral Angiography↗
PubMed1985

Fibroblastic tumor of the abducens nerve. Case report.

Tumors of the cranial nerves are uncommon, and are usually schwannomas or neurofibromas. The authors describe a case of a fibroblastic tumor involving the sixth cranial nerve. Based upon electron microscopy and immunohistochemistry, the tumor was not of nerve-sheath origin, but was comprised of fibroblasts. Clinical, radiographic, and pathological material are presented, and the literature is discussed. This represents the third case report of a tumor of the abducens nerve, and the first report of a fibroma of a cranial or peripheral nerve.

Abducens Nerve↗
PubMed1985

Transcallosal approach to the contralateral ventricle. Technical note.

Recent experience with an intraventricular arteriovenous malformation (AVM) demonstrated the usefulness of a transcallosal approach to the contralateral ventricle. Although this technique provides excellent exposure, its application has not been stressed in the literature. A brief description of the technique and its value is presented.

Adolescent↗
PubMed1985

Multiple intracranial aneurysms: determining the site of rupture.

A retrospective hospital chart and radiograph review was performed of all patients with multiple intracranial aneurysms seen over a 52-month period. Sixty-nine patients with a total of 205 aneurysms were studied. Among the patients with aneurysms, the incidence of multiple aneurysms was 33.5%. Multiple aneurysms were much more common in women, with a female to male ratio of 5:1 for all patients and 11:1 for patients with three or more aneurysms. Common locations for multiple aneurysms were the posterior communicating artery (22%), middle cerebral artery (21.5%), anterior communicating artery (12%), and ophthalmic artery (11%). However, locations with the highest probability of rupture were the anterior communicating artery (62%), posterior inferior cerebellar artery (50%), and basilar artery summit (50%). The middle cerebral artery was the least likely site for rupture. In contrast to previous studies, in this series irregularity of contour was more important than size in identifying the site of rupture. Using a simple algorithm outlined in the text, it was possible to identify the site of aneurysm rupture in 97.5% of cases.

Aged↗