Biomedical subjects

K M Welch

Publications and source records attributed to K M Welch.

At least 19 recordsLinked to original sources

PubMed1992

Further studies on platelet-mediated neurotoxicity.

The mechanism of ischemic neuronal injury is not fully resolved. The present view is that vascular occlusion per se does not fully account for the extent of neurological dysfunction. We hypothesized that platelet secretory products might contribute to ischemic neuronal injury in the central nervous system (CNS) (Joseph et al., Stroke, 20 (1989) 38-44 and 1316-1319). Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products, revealed that platelet product(s) had neurotoxicity. Further studies, using the same methods, were conducted here, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets), adding additional relevant controls including platelet membranes, red blood cells and washed rat platelets. The results confirmed our initial finding that an agent(s) in platelet secretion is neurotoxic. Subsequently, we identified serotonin (5HT), a major platelet product, as having toxic effects on neurons. This toxicity of 5HT appeared to be blocked by ketanserin, a 5HT2 receptor antagonist. Judging by the concentrations of 5HT that demonstrated neurotoxicity in these in vitro studies, it appears that products secreted from activated platelets could have pathological significance in vivo.

Animals↗

PubMed1992

Serotonin may have neurotoxic properties.

Serotonin (5HT), a major platelet secretory product, has been shown to suppress CNS function in vivo. As part of an ongoing project to study interactions between neuron and platelet, we used organotypic explant cultures of rat spinal cord to study if 5HT had a morphologically demonstrable neurotoxic effect. The results suggest that serotonin may be neurotoxic, and that this effect may be prevented by ketanserin, a specific 5HT2 antagonist. Related experiments, using acetylcholinesterase (AChE) enzyme activity as a biochemical parameter, indicate that 5HT hastens the decline of enzyme activity. The concentrations of 5HT at which neurotoxicity was demonstrated were comparable to the calculated 5HT concentration potentially present in the vicinity of an acute cerebral thrombus. These findings could provide new insight into the mechanism of ischemic neuronal injury.

Acetylcholinesterase↗

PubMed1992

Atraumatic quantitation of cerebral perfusion in cats by 19F magnetic resonance imaging.

We have noninvasively produced low-resolution, quantitative nuclear magnetic resonance images of cerebral blood flow in 2-ml voxels in eight cats. Typical signal-to-noise of 4 to 1 was obtained in cerebral voxels in 16.5-s epochs. Mean flow during normocapnia (paCO2 = 39 +/- 4 mm Hg) and hypercapnia (paCO2 = 62 +/- 4 mm Hg) was 53 +/- 20 ml/100 g-min and 140 +/- 36 ml/100 g-min, respectively. Fast flows in normocapnia were 94 +/- 13 and 182 +/- 39 ml/100 g-min in hypercapnia. These results suggest that an atraumatic quantitative imaging assessment of cerebral perfusion may be possible in humans using these techniques.

Animals↗

PubMed1992

Platelet activity and stroke severity.

Although platelets constitute the major component of a thrombus, its role in determining the clinical severity of thrombotic stroke is unknown. Therefore, we investigated the relationship between platelet ionized calcium ([Ca2+i]), a measure of platelet activity and presumably proneness to thrombosis, and clinical stroke severity in 45 consecutively studied acute ischemic stroke patients. Even though there was no correlation between the clinical neurological scores and the levels of baseline and activated platelet [Ca2+i], stroke was less severe in patients who had been taking aspirin at the time of stroke onset. These results raise several important questions: (a) is the extent of platelet activation a reflection of thrombus volume, (b) does the clinical severity of neurological deficit reflect the causative thrombus volume, and (c) whether the beneficial effect of aspirin in stroke prophylaxis is through its inhibition of platelets alone.

Aged↗

PubMed1992

The effects of post-ischemic hypothermia on the neuronal injury and brain metabolism after forebrain ischemia in the rat.

We investigated the effect of moderate post-ischemic hypothermia on neuropathological outcome and cerebral high energy phosphate metabolism, intracellular pH and Mg2+ concentration in the rat. Three groups of animals were investigated: (1) Wistar rats subjected to 12 min of forebrain ischemia under normothermic conditions (n = 17), (2) rats subjected to the identical procedure of ischemia, except that 30 degrees C hypothermia was induced post-ischemia and maintained for 2 h of reperfusion (n = 6), and (3) control hypothermic rats not subjected to ischemia (n = 4). In vivo 31P NMR spectroscopy was performed prior to ischemia, and at intervals up to 168 h after ischemia. Histological analysis of brain tissues was performed 7 days after ischemia. No significant differences in cortical and hippocampal neuronal damage was detected between the two experimental groups. Significantly lower pH values were detected in the hypothermic ischemic animals at 24 h (P = 0.0001) and 48 h (P = 0.018) post-ischemia compared to the normothermic ischemic animals. Normothermic ischemic animals exhibited significantly lower [Mg2+] at 72 h (P less than 0.006) compared to the pre-ischemia level. Our data indicate that post-ischemic hypothermia modifies the profiles of post-ischemic brain tissue pH and Mg2+ concentration, and this modification is not associated with histopathological outcome 7 days after ischemia.

Adenosine Triphosphate↗

PubMed1992

Headache associated with non-cephalic infections: classification and mechanisms.

A classification of headache associated with non-cephalic infections is proposed. The classification is supported by published case series and reports. The head pain can be explained by direct activation of pain producing mechanism by microorganisms or can be secondary to fever or to a combination of both.

Bacterial Infections↗

PubMed1992

Platelet catecholamines in cluster headache.

Platelet tyrosine and catecholamine (CA) content was measured in cluster headache sufferers during the different phases of the illness. Compared with controls, cluster headache sufferers had lower platelet levels of norepinephrine (NE) and epinephrine (E) in all phases of the syndrome. Tyrosine levels were increased significantly during the cluster headache attack. We suggest that these results provide biochemical evidence of sympathetic nervous system (SNS) hypofunction in cluster headache.

Adult↗

PubMed1992

Human focal cerebral ischemia: evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy.

The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.

Acidosis↗

PubMed1992

Study of platelet-mediated neurotoxicity in rat brain.

BACKGROUND AND PURPOSE: The mechanism of ischemic neuronal injury is not fully resolved. The present view is that vascular occlusion per se does not fully account for the extent of neurological dysfunction. We previously hypothesized that platelet secretory products might contribute to neuronal injury in the central nervous system. Our preliminary studies using organotypic rat spinal cord cultures exposed to human platelet and its secretory products revealed that platelet products had neurotoxic properties. METHODS: Further studies, using the same methods, were conducted, with the addition of several refinements such as use of gel-filtered platelets (as opposed to washed platelets) and adding additional relevant controls including platelet membranes, red blood cells, and washed rat platelets. RESULTS: Exposure of spinal cord explant cultures to platelet secretory products resulted in reduced number of neurons per ventral horn compared with control. CONCLUSIONS: Our findings suggest that platelet secretory products have neurotoxic properties. This effect was seen with platelet secretion obtained from physiological platelet concentrations. It appears possible that more abundant release of platelet products at the site of thrombus formation could have pathological significance in vivo.

Animals↗

PubMed1992

NMR spectroscopic and magnetoencephalographic studies in migraine with aura: support for the spreading depression hypothesis.

The authors propose that patients who suffer from migraine with aura have a susceptibility to spontaneous neuronal discharges and subsequent spreading depression. This is based upon a state of central neuronal excitability involving the excitatory neurotransmitter glutamate, in combination with supersensitivity of the N-méthyl-D-aspartate (NMDA) receptor. This hypersusceptibility is supported by increased turnover of high-energy phosphates, low intracellular Mg2+ and large amplitude depolarizing waves on magnetoencephalography (MEG).

Cortical Spreading Depression↗

PubMed1992

Cerebral blood flow changes with enalapril.

Patients with carotid artery occlusive disease (CAOD) may be at increased risk of iatrogenic cerebral hypoperfusion. Using the 133xenon-inhalation technique, we evaluated the effects of enalapril on regional cerebral blood flow (CBF) in 14 patients with chronic hypertension, 7 with CAOD and 7 without CAOD (no CAOD). Regional CBF and blood pressure were measured before and 60 minutes after a single dose of enalapril. Changes in mean arterial pressure after enalapril were not significantly different between the two groups: CAOD -4.67 +/- 8.7 mm Hg, no CAOD -6.18 +/- 8.2 mm Hg. Changes in mean CBF after enalapril were also not statistically different: CAOD -1.0 +/- 3.9, no CAOD 1.0 +/- 2.8. In the CAOD group only, however, changes in CBF were significantly related to increasing age (r = -0.9253, p less than 0.01), such that in patients 65 years or older CBF tended to decrease, whereas in younger patients it increased. Elderly patients with CAOD may be at increased risk of iatrogenic cerebral hypoperfusion, and it may be appropriate to evaluate prospectively the effects of antihypertensive medications on CBF.

Age Factors↗

PubMed1992

Magnetic resonance spectroscopy in cerebral ischemia.

Magnetic resonance spectroscopy (MRS) has been a fundamental and invaluable tool in the fields of chemistry and physics for over 40 years and has only been applied directly to the field of medicine in the last decade. MRS has contributed significant information on ischemic brain metabolism in the clinical patient. The potential of spectroscopy now extends to the diagnostic monitoring of metabolic change, in identifying markers of a therapeutic window, and establishing prognosis and outcome. This article presents a review of MRS studies of cerebral ischemia in clinical patients.

Blood Glucose↗

PubMed1991

Magnetic fields associated with anoxic depolarization in anesthetized rats.

We have performed simultaneous measurements of the DC-magnetoencephalogram (DC-MEG) and DC-electrocorticogram (DC-ECoG) in rats (n = 6) subjected to 90 s of reversible anoxia. The onset of major shifts of electric and magnetic signals occurred at 52 +/- 18 (S.D.) and 68 +/- 14 (S.D.), respectively, and reached a peak at 83 +/- 27 and 102 +/- 19 (S.D.) s, respectively, after termination of mechanical ventilation. DC-ECoG signal deflections were always associated with DC-MEG deflections. The time of onset and peak signals in both DC-MEG and DC-ECoG changes caused by asphyxia were highly correlated (r + 0.83, 0.94; P less than 0.05, 0.001; respectively). Our observations suggest that the non-invasive technique of DC-MEG is reliable and may provide insight into the mechanisms of anoxic cerebral depolarization.

Anesthesia, General↗

PubMed1991

Magnetic fields associated with spreading depression in anaesthetised rabbits.

Magnetic fields were measured with SQUID magnetometry outside the skull of anaesthetised rabbits during initiation and propagation of spreading depression (SD) in the cortex. Slowly changing fields (up to 1.4 pT) were observed during the propagation phase, from 4-8.5 min after initiation of SD with KCl application, with maxima at about 6 min. The peak amplitude of the equivalent net dipole generators in the brain was ca. 28 microA.mm, substantially less than previously observed with SD in vitro, but large enough that similar signals might be detectable in man.

Anesthesia, General↗

PubMed1991

19F NMR imaging of cerebral blood flow.

Techniques for the quantitative imaging assessment of cerebral blood flow are presented in a cat using 19F NMR imaging of trifluoromethane. The input function of the indicator was acquired noninvasively, while its uptake and clearance were followed in 2-cc volume voxels from images acquired at 67 s intervals. A single compartment model yielded normal cerebral blood flow estimates.

Animals↗

PubMed1991

Chronic changes in the brain Mg2+ concentration after forebrain ischemia in the rat.

Brain Mg2+ ion concentrations, [Mg2+], were evaluated in three groups of animals subjected to either 8 minutes (n = 10), or 12 minutes (n = 10) of near-complete forebrain ischemia, or sham operation (n = 10), from their 31P NMR spectra. No significant differences were observed in [Mg2+] among sham operated animals prior to or at any time point after surgery. In the 8-min ischemia group, mean [Mg2+] were significantly lower at 48 (0.28 +/- 0.06 mM, p = 0.014) and 72 (0.29 +/- 0.07 mM, p = 0.005) hours post-ischemia when compared to their mean pre-ischemia levels (0.39 +/- 0.08 mM). [Mg2+] was restored to pre-ischemia values at 96 hours after induction of ischemia. In the 12 min ischemia group, [Mg2+] were lower at all time points post-ischemia when compared to their pre-ischemia levels. Our data shows that forebrain ischemia causes a chronic decline of cerebral Mg2+ concentration, and the observed reduction of this cation can be partially attributed to concurrent brain tissue alkalosis.

Animals↗

PubMed1991

Endothelin-1 and human platelet activity.

Endothelin-1, a peptide produced by endothelium, causes vascular smooth muscle contraction possibly by mobilizing intracellular calcium. Shifts in ionized calcium may also play a role in platelet activation. Accordingly, the effects of endothelin on platelet ionized calcium and aggregation were studied. The measurements were made in aequorin-loaded gel-filtered human platelets derived from healthy donors. Endothelin even in a final concentration of 10(-6) M did not cause a measurable change in platelet ionized calcium or aggregation. When tested in combination with collagen, thrombin and platelet activating factor, endothelin showed no synergistic effect. These observations raise the possibility that endothelin may not interact with platelets in a physiologically significant way.

Adult↗

PubMed1991

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging.

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spin-spin relaxation time (T2), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T2 value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between "free" and "bound" water protons as measured by MTC imaging is at least partially responsible for the elevation in T2 values observed during ischemia, and may accompany breakdown of cellular structure.

Animals↗