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W Young

Publications and source records attributed to W Young.

At least 127 records · Page 7Linked to original sources
PubMed1990

Somatosensory evoked potentials in rat cerebral cortex before and after middle cerebral artery occlusion.

We recorded somatosensory evoked potentials in pentobarbital-anesthetized rats before and after middle cerebral artery occlusion. Trigeminal (vibrissae), median (forelimb), and sciatic (hind limb) nerve stimuli produced consistent, robust, and sharply localized responses in the trigeminal, forelimb, and hind limb regions of the somatosensory cortex of 18 rats. These regions are situated at sequentially greater distances from the center of infarcts produced by middle cerebral artery occlusion. In eight rats, occlusion 1-2 mm below the rhinal fissure abolished somatosensory evoked potentials in all three cortical region within minutes. Positive wavelets preceding the primary cortical response were also diminished by the occlusion, suggesting that ischemia affected the thalamocortical white matter. Four of these eight rats did not show histologically apparent ischemic involvement of the hind limb cortical region at 3 hours after occlusion; sciatic nerve evoked potentials recovered substantially in all four rats, and the amplitudes exceeded baseline (129 +/- 30% at 1 hour, 173 +/- 33% at 3 hours) in three of the four rats. Three of the eight rats did not have gross ischemic involvement of the forelimb cortical region; median nerve evoked potentials recovered fully in all eight rats, but the amplitudes did not exceed baseline. All eight rats had evidence of ischemic damage in the trigeminal cortex; no rat showed full recovery in this region, and all but one had trigeminal evoked potentials that were less than 20% of baseline amplitudes by 3 hours after occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Neural damage in the rat thalamus after cortical infarcts.

Histopathologic changes in the thalamus of 23 rats after somatosensory cortical infarction produced by middle cerebral artery occlusion were examined using the Fink-Heimer silver staining method, immunohistochemistry with antibodies against glial fibrillary acidic protein and laminin, and conventional stains. Middle cerebral artery occlusion produced cortical infarcts in the lateral parietal region, with variable involvement of the frontoparietal parasagittal sensorimotor cortex. Within 3 days after occlusion, massive terminal degeneration but no neuronal changes were apparent in the ipsilateral thalamus. By 1 week after occlusion, abnormal neurons with darkly stained, shrunken nuclei and atrophic perikarya were present in the ipsilateral thalamic nuclei. These neurons were densely argyrophilic in Fink-Heimer sections. Rats with small lateral parietal cortical lesions had degenerating neurons limited to the medial ventroposteromedial nucleus. Large lesions involving the parasagittal sensorimotor cortex resulted in widespread neuronal damage in the ventroposteromedial, ventroposterolateral, intralaminar, and posterior nuclear regions but nowhere else. Immunoreactivity to laminin antibody decreased, and astrocytic proliferation was abundant in affected thalamic areas. These findings are consistent with retrograde neuronal degeneration due to thalamocortical fiber damage in ischemic cortical regions. Such lesions remote from the infarct may influence functional recovery in patients with stroke.

Animals↗
PubMed1990

Congenital biliary dilatation: a spectrum of disease detailed by ultrasound.

Recently we have examined six children with the diagnosis of choledochal cyst who demonstrate a greater spectrum of biliary involvement than expected. Classically choledochal cysts have been divided into types and subtypes based on the configuration of common bile duct dilatation; however, this simplified information is misleading since surgical management is dependent on the exact extent of intrahepatic and extrahepatic biliary abnormalities. The pre-operative ultrasound examination must be meticulous to provide enough pertinent anatomic details. Much of the intrahepatic anatomy is not visualized at surgery nor on the operative cholangiograms where reflux of contrast into the intrahepatic ducts may not be consistently achieved.

Adolescent↗
PubMed1990

Cigarette sales to minors in Colorado.

In May of 1990, Secretary of Health and Human Services, Louis Sullivan, MD introduced model state legislation to restrict tobacco sales to minors. Without definitive actions, such as those suggested here and by Dr. Sullivan, tobacco use among Colorado's youth will continue to have almost unrestricted access to cigarettes and other tobacco products and our population will continue to suffer the harmful effects of tobacco well into the next century. If we act now to curb sales to minors, we will soon reap the benefits of our actions through reduced morbidity and mortality rates from cardiovascular disease, lung and other cancers, emphysema, other obstructive airways diseases and fires. Imagine an entire generation free of tobacco disease injury and death.

Adolescent↗
PubMed1989

Extracellular potassium activity and axonal conduction in spinal cord of the myelin-deficient mutant rat.

We recorded somatosensory evoked potentials SEPs), extracellular K+ ionic activity ([K+]e), and K+ clearance rates in the spinal cords of 14 myelin-deficient mutant rats and 16 normal male littermates at 16-41 days after birth. Tested under pentobarbital anesthesia (25 mg/kg ip) and hypothermic conditions (32-34 degrees C), myelin-deficient rats had longer cortical SEP latencies (67 +/- 20 ms) compared to those in normal siblings (48 +/- 15 ms; P less than 0.05). Mean baseline [K+]e levels were 2.6 +/- 0.5 mM in myelin-deficient rats and 2.6 +/- 0.8 mM in normal siblings. Clearance times of KCl solutions injected into the spinal cord were biphasic and exponential. The mean initial and secondary exponential half-times were 1.0 +/- 0.5 and 2.7 +/- 1.7 min for myelin-deficient rats and 0.8 +/- 0.4 and 3.8 +/- 3.2 min for normal siblings. Repetitive sciatic nerve stimulation (2-20 Hz, 2- to 6-s trains) produced 1-3 mM transient [K+]e rises in thoracic and lumbar cords of myelin-deficient rats. The [K+]e rises were largest in the dorsal spinal cord at 200-500 microns depth. The normal siblings had smaller or no stimulus-induced [K+]e rises. In myelin-deficient rats, injection of 1 mM 4-aminopyridine (4-AP) solution into the thoracic spinal cord completely suppressed the stimulus-induced [K+]e and markedly increased spinal and cortical SEP amplitudes for several hours. In the normal siblings, the 4-AP injections transiently blocked spinal conduction for 20-30 min but thereafter enhanced cortical SEP amplitudes for 2-3 h. We conclude that sciatic nerve stimulation produces spinal cord [K+]e rises in myelin-deficient rat larger than those in the normal siblings, that the [K+]e transients represent increased K+ release rather than impaired K+ clearance, and that the K+ ions come from 4-AP blockable sources.

4-Aminopyridine↗
PubMed1989

Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells.

Axonal morphometry of the lesion site was studied at 3 months after standardized weight-drop contusion injury of the thoracic spinal cord in adult cats. From a sample of 25 injured animals, 12 examples were found in which all surviving axons in the dorsal column were remyelinated by Schwann cells, at the level of the lesion. The dorsolateral tracts were also peripherally myelinated in 6 of these cases, and there was no central myelination in complete transverse sections through the lesion in four animals. In these cases, Schwann cell myelination was prevalent for several millimeters on either side of the lesion center. The extent of Schwann cell invasion correlated with the intensity of injury, measured by overall axon loss. Cortical somatosensory evoked potentials (CSEP) were recorded from all animals before and at intervals for 12 weeks after injury. CSEP to hindlimb (tibial nerve) stimulation were lost immediately at injury but some recovery took place during the first month. The extent of CSEP recovery correlated negatively but weakly with overall axon loss. Clear SEP were recorded at 3 months post-injury in 3 of the animals in which the dorsal columns were remyelinated by Schwann cells; in one of these, the dorsolateral funiculi were also peripherally myelinated. In another, oligodendrocyte myelination was absent from the entire transverse section of the lesion site. Thus, abnormal remyelination by cells of the peripheral nervous system, which is known to occur in a variety of central demyelinating conditions, is capable of restoring effective action potential conduction in mammalian spinal cord sensory tracts.

Animals↗
PubMed1989

Spinal cord sodium, potassium, calcium, and water concentration changes in rats after graded contusion injury.

Spinal cord Na, K, Ca, and H2O changes were measured 6 h after graded contusion injuries in 40 Sprague-Dawley rats. A 10 g weight was dropped 1.25 cm (n = 6), 2.5 cm (n = 7), 5.0 cm (n = 6), or 7.5 cm (n = 7) onto the thoracic spinal cord of 26 rats. An additional 10 rats served as laminectomy controls and 4 rats were unoperated controls. At 6 h after surgery or injury, the spinal cords were rapidly cut into 4 mm segments, weighed to obtain tissue wet weights (W), dried for 14-16 h at 97 degrees C in a vacuum oven (30 mmHg), and reweighed for tissue dry weights (D). Water concentrations ([H2O]d) were estimated from (W-D)/D in units of ml/g D. Ionic concentrations ([Na]d, [K]d, and [Ca]d) of the tissue samples were measured by atomic absorption spectroscopy with units of mumol/g D. Ionic shifts (delta [Na]d, delta [K]d, delta [Ca]d) were calculated by subtracting laminectomy control values from those measured in injured cords. Laminectomy alone significantly increased [Na]d and [H2O]d compared to unoperated controls. Mean +/- standard deviations of [H2O]d, [Na]d, [K]d, and [Ca]d were, respectively, 1.95 +/- 0.07, 182.6 +/- 5.9, 277.2 +/- 11.8, and 12.1 +/- 1.4 in unoperated controls; 2.12 +/- 0.08, 238.6 +/- 9.2, 277.8 +/- 9.2, and 11.7 +/- 1.1 in laminectomy controls. At the impact site, [K]d fell by 14-37% and [H2O]d rose by 14-24%, [Na]d by 13-64%, and [Ca]d by 65-137% of laminectomy control values. delta [Na]d, delta [K]d, and delta [Ca]d correlated linearly with impact velocities; [Ca]d increased by 1.0% per cm/sec (r = 0.995, p less than 0.005), [Na]d increased 0.67% per cm/sec (r = 0.950, p less than 0.01), and [K]d decreased 0.34% per cm/sec (r = 0.964, p less than 0.01). Neither delta [H2O] nor delta [Na]d + delta [K]d consistently predicted impact velocity. [Na]d + [K]d correlated with [H2O]d with a slope of 177.4 mumol/ml (r = 0.697, p less than 0.005). Since Na and K constitute greater than 95% of tissue inorganic ions, the slope approximates net ionic shift per ml of water entry or the ionic osmolarity of edema fluid. These results indicate that increasing contusions produce graded ionic shifts and that edema does not predict contusion severity. These data support our hypothesis that net ionic shifts cause edema in injured spinal cords.

Animals↗
PubMed1989

Corticofugal axonal degeneration in rats after middle cerebral artery occlusion.

We used the Fink-Heimer method to study degenerating corticofugal axons after unilateral middle cerebral artery occlusion in 14 adult male Long-Evans hooded rats. Axonal degeneration in the pyramidal tracts was prominent at 1-3 weeks, manifesting in well-defined silver-impregnated axonal bundles coursing from the internal capsule to the pyramids and crossing completely to the contralateral spinal cord. In half of eight rats examined at 1-3 weeks, the cortical infarct included the forelimb region of the sensorimotor cortex, and degenerating corticospinal axons could be traced to the lower cervical segments; in rats with involvement of the hindlimb cortical area as well, axonal degeneration extended to the lumbosacral segments. Terminal degeneration products were present in the forebrain, midbrain, and brainstem within 2 days after arterial occlusion; the number of degenerating terminals peaked at 7 days and decreased gradually thereafter up to 6 weeks. Dense terminal degeneration was observed in the trigeminal nuclear complex of all seven rats studied at 2 and 7 days. In these seven rats, five had small cortical infarcts, and silver-impregnated terminals were observed in the lateral reticular formation; in two rats with large cortical lesions, terminal degeneration was prominent in the medial reticular formation as well. We conclude that infarcts produced by middle cerebral artery occlusion cause axonal degeneration in the brainstem and spinal cord. The Fink-Heimer method may be useful for evaluating the rat middle cerebral artery occlusion model.

Animals↗
PubMed1989

Selective cortical neuronal damage after middle cerebral artery occlusion in rats.

We studied histopathologic changes in cerebral cortex of 20 rats after middle cerebral artery occlusion by using the Fink-Heimer suppressive silver impregnation method and conventional stains. At 6 hours after occlusion, Fink-Heimer-stained sections revealed abundant coarsely granular, intensely argyrophilic neurons in the ischemic cortex. These distinctive argyrophilic neurons could be clearly differentiated from neurons that suffered postmortem changes; argyrophilic neurons were present in all layers of the lateral parietal cortex but in only the superficial cortical layers II and III in the parasagittal area of the frontoparietal cortex and the temporo-occipital area. At 24 hours after occlusion as the ischemic region progressed to pannecrosis, argyrophilic neurons were still evident in peri-infarct regions, with more prominent neuritic silver deposits but no changes in number or spatial distribution. Over 2-7 days, the argyrophilic neurons gradually disappeared while many fine silver-impregnated degenerating terminals appeared in the peri-infarct regions. At 3-6 weeks after occlusion, no more argyrophilic neurons were seen in the cortex although degenerating axons were still present in the deep white matter. Our results indicate selective neuronal damage in the superficial cortical layers and massive axonal degeneration in the cerebrum surrounding infarcts. The neuronal damage does not appear to progress beyond 6 hours after middle cerebral artery occlusion. The Fink-Heimer method has many advantages over existing conventional stains for documenting selective neuronal damage in focal cerebral ischemia.

Animals↗
PubMed1988

Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats.

Our study describes the anatomy of the middle cerebral artery (MCA) in 65 Sprague-Dawley rats and the spatial distribution of ischemic cortical lesions caused by occluding major MCA branches. The rats characteristically had at least two major MCA branches, frontal and parietal. Many rats had additional branches supplying the pyriform and temporal cortexes. Permanent occlusion of the frontal or parietal branches combined with 30 minutes of bilateral carotid artery occlusion produced visible Evans blue dye uptake by ischemic cortical areas after 24 hours. No lesions distal to the occlusion were apparent in 38% and 43% of rats with frontal and parietal branch occlusions, respectively; small lesions contiguous with the occlusion site were observed in 38% and 32% of the rats. Only 6% of the frontal and 7% of the parietal branch occlusions produced isolated distal infarcts as expected if these branches were end-arteries. Blood flow was reversed in arteries distal to the occlusion. We conclude that extensive collateral connections of the frontal and parietal MCA branches with other arterial systems protect the anterior and posterior cortical regions. In contrast, occlusions of the pyriform branch of the MCA invariably caused infarcts in the frontopyriform region. In about one third of the rats, frontal or parietal branch occlusions produced lesions involving much of the proximal MCA territory; the frontopyriform region was most consistently affected. Combined, these data suggest that the pyriform MCA branch is an end-artery and that the cortical region it supplies is prone to ischemic damage resulting from any reduction of blood flow through the main MCA trunk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

21-Aminosteroid reduces ion shifts and edema in the rat middle cerebral artery occlusion model of regional ischemia.

U74006F is a member of a new family of steroid drugs called 21-aminosteroids, which are potent inhibitors of lipid peroxidation with little or no glucocorticoid or mineralocorticoid activity. We investigated the effects of U74006F on the early ionic edema produced by middle cerebral artery occlusion in rats. Intravenous doses of 3 mg/kg U74006F were given 10 minutes and 3 hours after occlusion. Tissue concentrations of Na+, K+, and water at and around the infarct site were measured by atomic absorption spectroscopy and by wet-dry weight measurements 24 hours after occlusion. Compared with vehicle treatment, U74006F treatment reduced brain water entry, Na+ accumulation, K+ loss, and net ion shift by 25-50% in most brain areas sampled in the frontal and parietal cortex. However, reductions of ionic edema were most prominent and reached significance (p less than 0.005, unpaired two-tailed t test) mostly in the frontoparietal and parietal cortex areas adjacent to the infarct site. Our findings suggest that a steroid drug without glucocorticoid or mineralocorticoid activity can reduce edema in cerebral ischemia but that the effects are largely limited to tissues in which collateral blood flow may be present.

Animals↗
PubMed1988

Nicardipine reduces calcium accumulation and electrolyte derangements in regional cerebral ischemia in rats.

We studied the effects of the calcium channel blocker nicardipine on regional tissue Ca2+, Na+, K+, and water shifts in the brains of seven Sprague-Dawley rats after permanent occlusions of the middle cerebral artery. We also assessed the entry of [14C]nicardipine into the brains of five rats; the highest concentrations of [14C]nicardipine were in the infarcted area. Nicardipine treatment significantly reduced Ca2+ accumulation in the middle cerebral artery territory by 60% compared with six untreated rats 6 hours after arterial occlusion. Eight 125-micrograms/kg boluses of nicardipine given every 30 minutes starting 5 minutes after arterial occlusion also significantly reduced the Na+ and K+ shifts in the middle cerebral artery territory by 40% and 50%, respectively, 6 hours after arterial occlusion. Nicardipine appears to reduce Ca2+ accumulation more than it reduces Na+ and water accumulation and K+ loss. Our results suggest that a calcium channel blocker can protect brain tissues in a model of focal cerebral infarction by directly reducing Ca2+ entry into ischemic cells.

Animals↗
PubMed1988

Dihydropyridine Bay K 8644 activates T lymphocyte calcium-permeable channels.

The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Bay K 8644 from 10(-9) to 10(-4) M caused a dose-dependent rise in the intracellular free Ca concentration, an effect that was not mimicked by the dihydropyridine Ca antagonist nifedipine. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. The predominant effect of Bay K 8644 on these channels was to increase the probability of channel reopening, apparently without a major effect on mean channel open-time. The results suggest that the dihydropyridine Ca agonist Bay K 8644 interacts with both voltage-gated and receptor-operated Ca channels and also suggest potential strategies for development of a new class of immunomodulatory drugs.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗