Search PubMed⌕ Search

Biomedical subjects

C G Wasterlain

Publications and source records attributed to C G Wasterlain.

At least 109 records · Page 6Linked to original sources

Neuronal response of the hippocampal formation to injury: blood flow, glucose metabolism, and protein synthesis.

The reaction of the hippocampal formation to entorhinal lesions was studied from the viewpoints of cerebral blood flow ([123I]isopropyl-iodoamphetamine[IMP])-glucose utilization ([14C]2-deoxyglucose), and protein synthesis ([14C]leucine), using single- and double-label autoradiography. Our study showed (i) decreased glucose utilization in the inner part, and increased glucose utilization in the outer part of the molecular layer of the dentate gyrus, starting 3 days after the lesion; (ii) increased uptake of [123I]IMP around the lesion from 1 to 3 days postlesion; and (iii) starting 3 days after the lesion, marked decrease in [14C]leucine incorporation into proteins and cell loss in the dorsal CA1 and dorsal subiculum in about one-half of the rats. These changes were present only in animals with lesions which invaded the ventral hippocampal formation in which axons of CA1 cells travel. By contrast, transsection of the 3rd and 4th cranial nerves resulted, 3 to 9 days after injury, in a striking increase in protein synthesis in the oculomotor and trochlear nuclei. These results raise the possibility that in some neurons the failure of central regeneration may result from the cell's inability to increase its rate of protein synthesis in response to axonal injury.

Amino Acids↗

Comparison of metabolic rates, language, and memory in subcortical aphasias.

Four patients with subcortical lesions and either aphasia or amnesia were compared to four patients with cortical lesions and aphasia. Each patient had [18F] fluorodeoxyglucose positron-emission computed tomography, language, and memory evaluations. Marked metabolic depression was found in the thalamus and caudate in all patients. The subcortical patients had only mild left-cortical changes, while the cortical patients showed marked cortical metabolic changes in the left hemisphere. Language changes were mild in the subcortical patients, while moderate to severe in the cortical patients. All patients showed severe verbal memory dysfunction. The only common abnormalities in the two groups were metabolic changes in the thalamus and severity of verbal memory dysfunction. These findings suggest a relationship between verbal memory and thalamic function.

Adult↗

Interactions between chemical and electrical kindling of the rat amygdala.

Holtzman rats were implanted with a chemitrode into the left basolateral amygdala, which could then be stimulated electrically (400 microA, 1 s, AC) or chemically by injection of carbachol (1 microliter, 2.7 nmoles, sterile, isotonic). Group A received a daily injection of carbachol and developed kindled seizures. Group B received carbachol mixed with equimolar atropine, which blocked seizures and kindling. After 20 injections, both groups were stimulated electrically once a day and kindled at similar rates. Two additional groups received electrical or sham stimulation, followed by carbachol kindling. No transfer effects were observed. Four additional groups received 27 nmoles of atropine through the chemitrode, followed 15 min later by electrical stimulation, sham stimulation, carbachol injection or saline injection, respectively. Atropine completely blocked carbachol kindling but did not alter the rate of electrical kindling. No different in the number of QNB binding sites was observed in the amygdala of rats sacrificed two weeks after full electrical kindling. The lack of interaction between electrical and carbachol kindling and the failure of atropine to block electrical kindling of the amygdala suggest that the activation of local muscarinic synapses, while essential for carbachol kindling, is not required for electrical kindling of the rat amygdala.

Amygdala↗

Measurement of local rates of brain protein synthesis by quantitative autoradiography: validation with L-[3H]valine.

Following the injection of 4-day old rats with 150 mM L-[3,4-3H]valine (10 mumol/g, IP) the incorporation of 3H into protein was linear 2 hours. Valine specific activity in the brain acid-soluble fraction was constant between 30 and 120 min after injection with a mean value of 82.3% of the injectate. Significant amounts of tritated metabolites accumulated in the brain acid-soluble fraction (41.4% of radioactivity at 120 min) but do not prove an impediment to measuring rates of protein synthesis. The rate of protein synthesis in cerebral cortex of the 4-day old rat was measured by quantitative autoradiography using [3H]valine and 3H-sensitive film. The measured rate shows excellent agreement with that found previously using L-[1-14C]valine. Our results suggest that [3H]valine can be a useful precursor to measure local rates of brain protein synthesis by quantitative autoradiography.

Animals↗

A quantitative autoradiographic method for the measurement of local rates of brain protein synthesis.

We have developed a new method for measuring local rates of brain protein synthesis in vivo. It combines the intraperitoneal injection of a large dose of low specific activity amino acid with quantitative autoradiography. This method has several advantages: 1) It is ideally suited for young or small animals or where immobilizing an animal is undesirable. 2 The amino acid injection "floods" amino acid pools so that errors in estimating precursor specific activity, which is especially important in pathological conditions, are minimized. 3) The method provides for the use of a radioautographic internal standard in which valine incorporation is measured directly. Internal standards from experimental animals correct for tissue protein content and self-absorption of radiation in tissue sections which could vary under experimental conditions.

Animals↗

Recent developments in the diagnosis and therapy of epilepsy.

Recent advances in the diagnosis of epilepsy include the development of a clinically useful classification of epileptic seizures and the recognition of specific epileptic disorders. These advances have been aided by the advent of x-ray computed tomography, long-term electroencephalographic telemetry, and video monitoring. Techniques for functional imaging of the human brain promise even greater diagnostic capabilities. New antiepileptic drugs have improved medical management, and technical and theoretical advances in pharmacokinetics have permitted physicians to design balanced dosing for individual patients. Although currently underused, surgical treatment of partial complex epilepsy can be safe and effective when used appropriately. Operant conditioning of electroencephalography may become another practical alternative therapy. Contributions of basic research to understanding the complications of status epilepticus have influenced treatment protocols and greatly improved the prognosis of this potentially lethal condition.

Anticonvulsants↗

Kindling: a pharmacological approach.

Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.

Amygdala↗

FDG positron emission computed tomography in a study of aphasia.

Positron emission computed tomography (PECT) using 18F-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the correlations between clinical status, anatomy (as described by CT), and metabolism in five patients with stable aphasia resulting from ischemic cerebral infarction. Local cerebral metabolic activity was diminished in an area larger than the area of infarction demonstrated by CT. In one patient, FDG PECT revealed a metabolic lesion that probably caused the aphasic syndrome and was not apparent by CT. The data suggest that reliance on CT in delineating the extent of the brain lesion in aphasia or other neuropsychological defects can be misleading; FDG PECT may provide important additional information. Two patients with similar metabolic lesions had very different clinical syndromes, showing that even when currently available methods are combined, major gaps remain in clinicoanatomical correlations in aphasia.

Aged↗