Effects of middle cerebral artery occlusion on cerebral cortex choline and acetylcholine in rats.

Background and Purpose The purpose of this study was to investigate the behavioral changes, in particular retention of memory, after focal cerebral ischemia in rats.Methods Ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). For quantitative behavioral analysis, one-trial passive avoidance response and active avoidance response with the discrete lever-press avoidance procedure were observed. One group of animals was trained once to learn the passive avoidance task 1 day before surgery. The response latency was examined 4 and 14 days after surgery. The second group was trained to learn the active avoidance task for 2 weeks before surgery. The avoidance rate was examined 3 and 14 days after surgery.

Section: Discussionsupporting

confidence: 62%

Disturbance of retention of memory after focal cerebral ischemia in rats.

Hirakawa

Tamura

Nagashima

et al. 1994

“…Enhanced choline production has been found to be limited to brain tissue fractions containing membranes. 46 A recent in vitro experiment found that choline levels were not decreased by treatment with an acetylcholinesterase inhibitor during ischemia, implying that phospholipid membrane breakdown and not acetylcholine metabolism was responsible for the rise in choline. 48 These studies suggest that increases in trimethylamine signal may arise from cell membrane breakdown.…”

Section: Ppmmentioning

confidence: 99%

Proton magnetic resonance spectroscopy of cerebral lactate and other metabolites in stroke patients.

Graham

Blamire

Howseman

et al. 1992

172

Background and Purpose: Proton magnetic resonance spectroscopy can measure in vivo brain lactate and other metabolites noninvasively. We measured the biochemical changes accompanying stroke in 16 human subjects with cortical or deep cerebral infarcts within the first 3 weeks after symptom onset, and performed follow-up studies on six.Methods: One-dimensional proton spectroscopic imaging encompassing the infarct region was performed with a 2.1-T whole-body magnet using the stimulated echo pulse sequence and an echo time of 270 msec.Results: All but one of the cortical stroke patients had increased lactate within or near the infarct. Persistently elevated cerebral lactate was documented in five of six cases studied serially as long as 251 days after infarction. iV-acetylaspartate levels were decreased in most cortical strokes. Elevated lactate, accompanied by minimal reduction in iV-acetylaspartate, was recorded in two of four patients in the first week following a small subcortical infarct.Conclusions: Long-term elevation of lactate commonly occurs after stroke. This lactate may arise from ongoing ischemia or infiltrating leukocytes, or it may be a residual of the lactate formed during the initial insult. The ability to observe stroke-elevated lactate pools at any time after lesion onset provides an approach to distinguishing among these possibilities in the future. (Stroke 1992;23:333-340) KEY WORDS • cerebral infarction • lactates • nuclear magnetic resonance

“…5 The difference between that decrease and the presently reported larger decrease in tissue acetylcholine content is probably related to the fact that CBF levels attained during four-vessel occlusion are lower than those obtained with MCA occlusion. Although we did not measure CBF during ischemia in the present experiments, data in the literature indicate that blood flow in the rat cerebral cortex is <0.04 mlxg^xmin" 1 with four-vessel occlusion 9 while our previous experiments with MCA occlusion showed a minimum of 0.2 mlxg^xmin" 1 .…”

Section: Resultsmentioning

confidence: 61%

“…Acetylcholine, choline, and [ M C]IAP were extracted from these homogenates and assayed by gas chromatography/mass spectrometry (acetylcholine and choline) or liquid scintillation counting ([ 14 C]IAP) as described in detail elsewhere. 5 Regions dissected were the dngulate cortex, medial frontoparietal cortex, lateral frontoparietal cortex, olfactory cortex, rostral hypothalamus, medial striatum, lateral striatum, hippocampal CA1 region, and hippocampal CA2 region. All regions were sampled in both cerebral hemispheres.…”

Section: Methodsmentioning

confidence: 99%

Time-dependent changes in cerebral choline and acetylcholine induced by transient global ischemia in rats.

Scremin

Jenden

1991

Self Cite

We occluded the carotid and vertebral arteries of 12 rats for 15 minutes to measure the brain concentrations of choline and acetylcholine and cerebral blood flow at the end of the ischemic period or 15,30, or 150 minutes after circulation was reestablished. The animals were sacrificed with microwave radiation focused to the head immediately after a brief infusion of [ 14 C]iodoantipyrine with rapid sampling of arterial blood. Brain tissue samples were extracted with ether to separate the tracer, which was subsequently measured by liquid scintillation counting and used to calculate local cerebral blood flow. The aqueous phase was then processed for the measurement of choline and acetylcholine concentrations by gas chromatography/mass spectrometry. The results showed a large increase in tissue choline content and a decrease in tissue acetylcholine content during ischemia. During recirculation, choline levels progressively declined, reaching levels lower than those in four control rats after 150 minutes of recirculation for most brain regions. A reciprocal relation between the brain choline concentration and local cerebral blood flow was found. Acetylcholine levels showed an initial rebound to greater than control during recirculation, with subsequent normalization. Brain acetylcholine concentration was positively correlated with brain choline concentration, provided that cerebral blood flow was >03 mlxg'xmin" 1 . Because tissue free choline was depleted in most brain regions 150 minutes after transient ischemia, we speculate that prolonged ischemia may produce a greater depletion of tissue free choline with a resulting decline in tissue acetylcholine. This could play an important role in the cognitive deficit associated with vascular dementia. (Stroke 1991^22:643-647) A cetylcholine is a neurotransmitter of crucial importance in the central nervous system. Only a few studies have addressed alterations in the cerebral concentrations of this molecule under ischemic conditions. The concentrations of both precursors of acetylcholine, choline and acetylcoenzyme A (acetyl-CoA), are known to be affected by the level of cerebral blood flow (CBF). Within the brain, choline is continuously produced by hydrolysis of phospholipids and acetylcholine and reutilized for synthesis of phospholipids and acetylcholine. These processes normally result in a net production of free choline that is washed away by the circulation and is reflected in a higher cerebral venous than arterial concentration.1 -4 As a consequence, an inverse rela- Received October 16, 1990; accepted January 23, 1991. tion between CBF and tissue choline level occurs during focal cerebral ischemia. 3 This effect tends to enhance the rate of acetylcholine synthesis by a precursor-loading mechanism when CBF decreases. Acetyl-CoA used for acetylcholine synthesis, on the other hand, originates from pyruvate, the concentration of which is known to decrease during ischemia. 6 Thus, a reduction of CBF will potentially affect acetylcholine synthesis in opposite ways by...