The systemic administration of norepinephrine has minimal effects on the cerebral circulation, perhaps due to blood-brain barrier mechanisms. To test hypothesis, the cerebrovascular effects of norepinephrine beyond the blood-brain barrier were studied in anesthetized baboons, Intraventricular norepinephrine (40 mug/kg) resulted in significant increases in cerebral blood flow (40%), cerebral oxygen consumption (21%), and cerebral glucose uptake (153%). Intracarotid hypertonic urea opens the blood-brain barrier by osmotic disruption; Consequent to hypertonic urea, the intracarotid infusion of norepinephrine, 50 ng/kg-min, significantly increase cerebral blood flow (49%), cerebral oxygen consumption (21%), and cerebral glucose uptake (76%), It appears probable that the cerebrovascular responses to norepinephrine are dependent on the integrity of the blood-brain barrier; It is likely that the increase in cerebral blood flow, associated with norepinephrine when it bypasses the barrier, is secondary to an increase in cerebral metabolism.

Animals↗

PubMed1976

Influence of endogenous norepinephrine on cerebral blood flow and metabolism.

The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been shown to effect pronounced changes in the cerebral circulation. Reserpine (40 mug/kg, by intracarotid infusion) was administered in order to release brain norepinephrine in five anesthetized baboons. Reserpine significantly increased cerebral oxygen consumption (23%) and cerebral blood flow (50%). This response lasted for approximately 60 min. In a further five animals, effects of central beta-adrenoreceptor blockade were studied. Pro pranolol (12 mug/kg-min) produced an immediate, significant reduction in both cerebral oxygen consumption (40%) and cerebral glucose uptake (39%). Cerebral blood flow was reduced minimally. However, the responsiveness of the cerebral circulation to induced hypercapnia was severely attenuated from a gradient of 3.22 before, to 1,11 after, administration. These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.

Animals↗

PubMed1970

A three-year review of household wringer injuries.

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Accidents, Home↗

PubMedDate not supplied

123Iodo-MK-801: a spect agent for imaging the pattern and extent of glutamate (NMDA) receptor activation in Alzheimer's disease.

Glutamate, and the NMDA glutamate receptor, may be involved in Alzheimer's Disease (AD). Reductions in NMDA receptors are found in AD, possibly contributing to memory deficits. However the NMDA receptor is involved in excitotoxicity, which may play a role in cell death and the production of neurofibrillary tangles in AD; although with lower levels of glutamate than occur in cerebral ischaemia. Therefore reductions in the NMDA receptor may worsen memory deficit in AD, but increased stimulation of the receptor may contribute to the progress of the disease. MK-801 has been used to image excessive glutamate activation following ischaemia in rats. However, it is unclear how effective MK-801 is in conditions with lower levels of glutamate release. This study attempts to gain insight into the utility of the tracer in these conditions, exploring glutamatergic mechanisms in AD. It describes the retention and elimination of 123iodo-MK-801 in five AD and five control subjects, comparing this to regional cerebral blood flow (rCBF). The initial uptake of 123I-MK-801 is dominated by delivery of the ligand. However, despite significant reductions in rCBF in the AD patients, there is no significant difference in the uptake of 123I-MK-801. This suggests increased retention of 123I-MK-801 in the AD patients. In addition the washout of 123I-MK-801 was less in the AD patients, again suggesting increased retention, although this only reached significance in one region. Theses data hint at possible increases in NMDA activation in AD but ultimately 123I-MK-801 does not provide a sufficiently accurate measurement to demonstrate this conclusively. Further NMDA ligands are now at a late stage of development and may provide more conclusive answers to the role of glutamate in AD.

Aged↗

PubMedDate not supplied

Neurobiology. Peptides and the microregulation of blood flow in the brain.

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Animals↗

PubMedDate not supplied

A functional role for vasoactive intestinal polypeptide in anterior cingulate cortex.

Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the cerebral cortex, where it is the putative neurotransmitter of a major intracortical neuronal system. Homogenates of cortical tissue contain high-affinity, specific binding sites for VIP as well as an adenylate cyclase system which is sensitive to this peptide. As with many of the other peptidergic systems which have been identified in the central nervous system (CNS), it has proved extremely difficult to elucidate the nature and extent of the functional role of VIP in specific brain areas. Here, using the quantitative autoradiographic 14C-deoxyglucose technique in rats to provide insight into functional processes, we describe the increases in glucose utilization which occur locally in anterior cingulate cortex following the unilateral injection of VIP (20 pmol) into this key brain area and, additionally, the focal alterations in glucose use in CNS regions having known neuronal connections with the injected region (for example, ipsilateral mediodorsal thalamus, ventral tegmental area, nucleus accumbens, caudate nucleus and contralateral cingulate cortex). These data provide evidence that VIP may modify the processing of afferent and efferent information within the anterior cingulate cortex in the conscious rat.

Animals↗

PubMedDate not supplied

Correlation of triphenyltetrazolium chloride perfusion staining with conventional neurohistology in the detection of early brain ischaemia.

Triphenyltetrazolium chloride (TTC) has been used to detect experimental brain ischemia but its accuracy has not been established fully, especially in models of early brain ischaemia. We have developed a technique that combines TTC-staining and perfusion-fixation with formalin in the same specimen. The left middle cerebral artery of 12 rats, anaesthetized with halothane were exposed via a subtemporal approach and occluded for 4 h. The animals were perfused transcardially with TTC (2%) and formalin (10%). The forebrain was sliced and the size of the ischaemic area, delineated by TTC, was measured. The brain slices were then processed for light microscopy, and the amount of ischaemic damage determined. The ischaemic volumes of the hemisphere and cortex assessed by TTC (127.4 +/- 21.7 mm3 and 18.4 +/- 3.0 mm3) were larger than the volumes measured by microscopy (104.3 +/- 16.6 mm3 and 15.2 +/- 3.6 mm3) but there was no statistical difference between them. Correlation of the ischaemic volumes in hemisphere and cortex between the two methods was good (r2 = 0.9221, P less than 0.01 and r2 = 0.9243, P less than 0.001), but the correlation of the ischaemic areas at specific coronal planes was poor. The ischaemic volume of caudate nucleus measured by TTC (15.2 +/- 3.6 mm3) was smaller than the volume assessed by microscopy (18.4 +/- 3.0 mm3) and the correlation was poor (r2 = 0.6650) It is concluded that TTC-staining provides only an approximation of the amount of early ischaemic brain damage subsequently identified by conventional light microscopy.

Animals↗

PubMedDate not supplied

Cerebral ischemia induces alterations in tau and ubiquitin proteins.

Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.

Animals↗

PubMedDate not supplied

The distribution of ischaemic damage and cerebral blood flow after unilateral carotid occlusion and hypotension in the rat.

We have developed a model of haemodynamic cerebral ischaemia by inducing haemorrhagic hypotension (40-50 mmHg mean blood pressure) following unilateral common carotid occlusion, with external carotid ligation, in anaesthetised rats. The neuropathological pattern of ischaemic brain damage was correlated with the distribution of change in cerebral blood flow using the 14C-iodoantypyrine autoradiographic technique. Whereas hypotension alone (40-50 mmHg) resulted in neither ischaemic brain damage nor significant alterations in cerebral blood flow, the combination of this degree of hypotension with unilateral carotid occlusion produced predominantly unilateral ischaemic brain damage which correlated with regions of reduced cerebral blood flow. With this type of haemodynamically induced oligaemia, the most vulnerable areas were the lateral neocortex, the caudate nucleus, the hippocampus and the thalamus. Within the cortex, the greatest reductions in blood flow occurred in the deeper cortical layers, and this was the most frequent site of ischaemic cell change. These data support the concept of a haemodynamic mechanism in the pathogenesis of some transient cerebral ischaemic attacks in man.

Animals↗

PubMedDate not supplied

Vasomotor effects of dimethyl sulfoxide on cat cerebral arteries in vitro and in vivo.

We studied the direct vascular effects of dimethyl sulfoxide (DMSO) in isolated middle cerebral arteries and on pial arteriolar caliber after subarachnoid perivascular microinjection in chloralose-anesthetized cats, and on brain retraction in cats given DMSO intravenously. DMSO did not constrict isolated cerebral arteries at any of the concentrations studied (10(-10) to 4 X 10(-1) M). In middle cerebral arteries precontracted with potassium, 5-hydroxytryptamine, prostaglandin F2 alpha, or with mechanically raised tone, DMSO at concentrations of 10(-10) to 10(-2) M had no significant effects; at concentrations greater than 10(-2) M, DMSO consistently relaxed the arteries, probably because of the hyperosmolarity of the bathing solution. Microapplication of DMSO (10(-6) to 10(-2) M) around pial arterioles on the cortical surface did not change arteriolar caliber significantly. Higher concentrations of DMSO (1%) increased arteriolar caliber by 56 +/- 4% (p less than 0.001), probably as a consequence of solution hypertonicity. DMSO did not modify in vivo cerebrovascular responses to alterations in perivascular potassium ion concentrations. Intravenous administration of DMSO did cause obvious brain shrinkage. These data provide no support for the view that direct cerebral vascular effects play a major role in the clinical efficacy of DMSO, but are consistent with the hypothesis that DMSO's ability to lower intracranial pressure derives from its osmotic effect on cerebral issue.

Animals↗

PubMedDate not supplied

Lumbar spondylolysis. A study of natural progression in athletes.

We examined the natural course of athletically active young people with back pain and a diagnosis of spondylolysis (stress fracture of the pars interarticularis of the facet joint of the lumbar spine). We limited the study to those with "subtle" fractures (normal radiographs and positive bone scans) and used computed tomography scanning to further characterize this lesion and to determine whether we could demonstrate healing in this population. The study group included 40 patients with low back pain and a diagnosis of spondylolysis by nuclear medicine study. Computed tomography scans were performed with both traditional cuts and reverse-gantry angled cuts to help determine long-term treatment and prognosis. Forty-five percent of patients (18) demonstrated chronic nonhealing fractures, 40% (16) demonstrated acute fractures in various stages of healing, and 15% (6) demonstrated no obvious fractures. With the diagnosis of spondylolysis being fairly common in young athletes with low back pain, primary care physicians need to have a high index of suspicion in making the diagnosis. Computed tomography scans can play a very important role in diagnosis, assessment of the defect, short-term and long-term management decisions, and in determining prognosis.

Adolescent↗