Cortical Acetylcholinesterase Activity Research Articles

Sensorimotor deficit and cholinergic changes following coexposure with pyridostigmine bromide and sarin in rats.

A myriad of neurological symptoms including muscle and joint pain, ataxia, chronic fatigue, headache, and difficulty in concentration have been reported by Persian Gulf War (PGW) veterans. A large number of these veterans were prophylactically treated with pyridostigmine bromide (PB) and possibly exposed to sarin. In the present study we investigated the effects of PB and sarin, alone and in combination, on sensorimotor performance and the central cholinergic system of rats. Male Sprague-Dawley rats were treated with PB (1.3 mg/kg, 15 daily doses, oral) and sarin (50, 75, 90, and 100 microg/kg, single im dose on day 15), alone and in combination. The animals were evaluated for postural reflexes, limb placing, orienting to vibrissae touch, incline plane performance, beam-walk time, and forepaw grip time 7 and 15 days following treatment with sarin. Treatment with either PB or sarin alone resulted in significant sensorimotor impairments. Coexposure to sarin and PB resulted in significant sensorimotor deficits that worsened over time. By 15 days following sarin treatment, plasma butyrylcholinesterase (BChE) activity returned to normal levels in the animals treated with sarin alone, whereas in the animals exposed to PB or PB plus sarin, there was an increase in the enzyme activity. Cortical acetylcholinesterase (AChE) activity remained inhibited in the animals treated with sarin alone and in combination with PB. Muscarinic acetylcholine receptor (m2 mAChR) ligand binding with [(3)H]AFDX-384 in cortex and brain stem showed significant increases (approximately 120-130% of control) following coexposure to PB and sarin at higher doses. To evaluate the potential of PB for augmentation or inhibition of the toxicity induced by acute sarin exposure, the animals were exposed to either 10 or 100 microg/kg sarin (single im injection) with or without pretreatment with PB, and sacrificed 3 h after treatment with sarin. Pretreatment with PB offered slight protection in the plasma as well as brain regional enzyme activities. Pretreatment with PB did not have any effect on sarin-inhibited brain regional AChE activity following treatment with 100 microg/kg sarin. These results show that prophylactic treatment with PB offers some degree of protection in peripheral cholinesterase. Furthermore, these results show that treatment with either sarin or PB alone resulted in sensorimotor impairments, while coexposure to high doses of sarin with PB caused an exacerbated deficit.

Management of Alzheimer??s Disease

Alzheimer’s disease affects 15 million people worldwide. As the elderly population grows, the incidence of Alzheimer’s disease will also increase. It is estimated that by 2010, 40 million US citizens will be over the age of 65 years and by 2040, it is predicted that 14 million US citizens will have Alzheimer’s disease. There is currently no treatment which stops or delays the progression of this condition; however, anticholinesterase therapy provides some symptomatic relief. The cognitive impairment experienced by patients with Alzheimer’s disease is partially due to degeneration of cholinergic pathways within the CNS and therefore symptomatic treatments have focused on restoring cholinergic inputs. Donepezil is a second generation anticholinesterase drug which reduces cortical acetylcholinesterase activity and improves, or at least slows the decline in, cognitive functioning in patients with Alzheimer’s disease. In patients with mild to moderate Alzheimer’s disease, treatment with donepezil (5 to 10 mg/day) for 1 year extended the median time to a clinically evident functional decline by 5 months compared with treatment with placebo. In addition, patients receiving donepezil have also shown significant improvement in ratings of global function, cognition, activities of daily living and disease severity over a 1-year period (p < 0.05 in each case). In patients with moderate to severe Alzheimer’s disease, donepezil significantly improved ratings of behavior compared with placebo (p < 0.05). Donepezil treatment is associated with the well recognized adverse events which accompany cholinergic therapy. The most frequently reported adverse events with donepezil treatment are gastrointestinal complaints such as nausea, diarrhea and vomiting, and CNS conditions including dizziness, headache and insomnia. These adverse events are typically mild and transient. Preliminary data from a direct comparison of donepezil and rivastigmine suggests that donepezil may exhibit an improved tolerability profile compared with rivastigmine. Recent data suggest that use of donepezil is associated with a significant delay in the time to institutionalization. Data from modeling and pharmacoeconomic studies also predict that use of donepezil may lead to a reduction in costs. However, it is likely that these savings will be distributed across multiple healthcare and non-healthcare systems and may not be fully represented in the budgets of those who are responsible for the direct costs of providing this medication. Donepezil is the only cholinesterase inhibitor currently available in a once daily formulation and with a relatively simple dose escalation schedule. This regimen coupled with a good tolerability profile makes donepezil a first-line treatment for patients with mild to moderate Alzheimer’s disease. However, only direct comparisons between donepezil and other second generation anticholinesterases will provide definitive data which can be used to maximize patient outcomes. In addition, wider clinical experience with donepezil may help to identify a subgroup of patients who respond strongly to treatment thus improving patient care and reducing costs.

The contribution of mild thiamine deficiency and ethanol consumption to central cholinergic parameter dysfunction and rats' open-field performance impairment

We studied at the biochemical, morphological, and behavioral levels the effect of chronic ethanol consumption, associated or not with a mild thiamine deficiency episode. We found that (i) thiamine deficiency induced a significant decrease of the acetylcholinesterase (AChE) activity both in cortex and hippocampus; (ii) chronic ethanol treatment has no effect on cortical AChE activity, but induced a significant decrease of hippocampal enzyme activity; (iii) the reduction in cortical and hippocampal AChE activity induced by chronic ethanol treatment associated with a 1-week thiamine deficiency was also significant and was greater than that induced by ethanol alone. Furthermore, either chronic ethanol or thiamine deficiency induced a significant decrease in the release of acetylcholine (ACh) in the stimulated condition using high potassium concentration; and when both treatments were associated the decrease was even greater. In the unstimulated condition, the reduction in the release of ACh was greater for ethanol treatment than for thiamine deficiency. Open-field tests showed that only in the “sniffing” category were there significant differences among the experimental groups. No morphological change was detected by optical microscopy, suggesting that the injury process was in its initial stages in which only functional and behavioral changes are displayed. In addition, our biochemical results indicate that cortical cholinergic susceptibilities to ethanol and thiamine deficiency are significantly different.

The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats

Thousands of soldiers who served in the Gulf War have symptoms that have been collectively termed Gulf War Illness (GWI). It has been suggested that a combination of operational stress and pyridostigmine, a drug given as a pretreatment to protect soldiers against the effects of exposure to nerve agents, might have had unexpected adverse health effects causing these symptoms. Our laboratory has previously modeled operational stress in rats using a paradigm of around-the-clock intermittent signalled footshock. In the present studies, this model was used to investigate the potential synergistic effects of chronic stress and pyridostigmine on physiology and behavior. Seventy-two rats were trained to perform an alternation leverpressing task to earn their entire daily food intake. The rats were then implanted with osmotic minipumps containing vehicle, pyridostigmine (25 mg/ml pyridostigmine bromide) or physostigmine (20 mg/ml eserine hemisulfate). The pumps delivered 1 μl/h, which resulted in a cumulative dosing of approximately 1.5 mg/kg/day of pyridostigmine or 1.2 mg/kg/day of physostigmine, equimolar doses of the two drugs. The rats were then returned to their home cages where performance continued to be measured 24 h/day. After 4 days, 24 of the 72 rats were trained to escape signalled footshock (avoidance-escape group) and 24 other rats (yoked-stressed group) were each paired to a rat in the avoidance-escape group. The remaining 24 rats were not subjected to footshock (unstressed group). Shock trials were intermittently presented in the home cage 24 h/day for 3 days, while alternation performance continued to be measured. Since only 12 test cages were available, each condition was repeated to achieve a final n of six rats per group. Pyridostigmine and physostigmine each decreased blood acetylcholinesterase levels by approximately 50%. Physostigmine also decreased brain cortical acetylcholinesterase levels by approximately 50%, while pyridostigmine had no effect on cortical acetylcholinesterase activity. Alternation performance was impaired on the first day of stress and then recovered. Neither pyridostigmine nor physostigmine affected performance in the absence of stress or increased the effects of stress alone. Corticosterone was significantly increased in the yoked stress group compared to unstressed controls. These data suggest that pyridostigmine does not exacerbate the effects of stress on performance or levels of stress hormones. Furthermore, these data do not suggest that stress enables pyridostigmine to cross the blood brain barrier.

Effect of stereochemistry on ester hydrolysis by cholinesterases: Implications for radiotracer design

There is currently great interest in developing radiotracers to estimate cortical acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymatic activity in Alzheimer’s disease patients using in vivo imaging. As part of an ongoing effort to define structure-activity relationships (SAR) for cholinesterase substrates, we have recently published in vitro and in vivo kinetic results for a series of I-[”C]methyl-4-piperidinyl esters (1). These data exhibited the expected preference of AChE for short-chain esters (acetate and propionate) and the specificity of longerchain esters (butyrate and pentanoate) for BuChE. We have also shown that this general pattern of selectivity extends to the l-methylr3pyrrolidinyl esters, la,b (2). As these latter compounds are chiral, it was of interest to extend the SAR to include the effects of stereochemistry on enzyme selectivity and cleavage rates.

Limited donepezil inhibition of acetylcholinesterase measured with positron emission tomography in living Alzheimer cerebral cortex

Based on surrogate assays of peripheral red blood cells, reports state that widely prescribed doses of donepezil hydrochloride provide nearly complete inhibition of cerebral cortical acetylcholinesterase activity in the treatment of Alzheimer's disease (AD). To test this, direct positron emission tomography measures of cerebral acetylcholinesterase activity were made in AD patients before and after treatment with donepezil (5 and 10 mg/day) for at least 5 weeks and compared with similar measures in normal controls who were untreated or after acute administration of another AChE inhibitor, physostigmine salicylate (1.5 mg/hr). After physostigmine, acetylcholinesterase inhibition averaged 52% in normal cerebral cortex. After donepezil, cerebral cortical inhibition in AD brain averaged only 27%. Clinical trials of this donepezil dose schedule are not testing the effect of nearly complete cerebral cortical inhibition.

Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: A positron emission tomography study

We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11–labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD. Ann Neurol 2000;48:194–200

Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: A positron emission tomography study

We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD.

Triggering of soman-induced seizures in rats: Multiparametric analysis with special correlation between enzymatic, neurochemical and electrophysiological data

Soman, an anticholinesterasic neurotoxic drug, induces epileptic seizures during severe intoxication. The neuropathological lesions then observed are linked to the appearance of these seizures, but their trigger conditions still remain unknown and a great variability between animals is observed. We have developed a technique allowing, in freely moving rats, the in vivo determination of three sets of neurophysiological data, before and during a soman intoxication. For the same rat, we associated cortical acetylcholinesterase (AChE) activity by microdialysis with both the assay of extracellular acetylcholine (ACh) concentrations and electroencephalographic (EEG) recording and power spectrum analysis (gamma band). Data have been analyzed to define the critical parameters which lead to the epileptic fit. Although we found thresholds for seizure occurrence, AChE inhibition having to be over 65% and ACh over 200-fold the baseline, these two criteria are not sufficient to predict the appearance of seizures. Only animals with no increase of energy in the gamma band early after soman poisoning will then exhibit an epileptic fit. Gamma band energy is modulated by noradrenergic activity and might be related to the sympathetic response to stress. So we can hypothesize, that the variation of energy in gamma band after intoxication, which might be related to stress adaptation strategy, may determine whether or not the animal will exhibit an epileptic fit.

Implication of gamma band in soman-induced seizures.

Soman, an anticholinesterasic neurotoxic drug, induces epileptic seizures during severe intoxication. Their trigger conditions still remain unknown and a great variability between animals is observed. The butterfly model in the catastrophe theory has been used to explain these triggering conditions. We have developed a technique allowing, in freely moving rats, the "in vivo" determination of three sets of neurophysiological data, followed before and during a soman intoxication. For the same rat, we associated cortical acetylcholinesterase (AChE) activity by microdialysis with both the assay of extracellular acetylcholine (ACh) concentrations and electroencephalographic (EEG) recording and power spectrum analysis (gamma band). Data have been analysed to define the critical parameters which lead to the epileptic fit. Although we found thresholds for seizure occurrence, AChE inhibition having to be over 65% and ACh over 200 fold the baseline, these two criteria are not sufficient to predict the appearance of seizures. Only animals with no increase of energy in the gamma band early after soman poisoning will then exhibit an epileptic fit. The butterfly model provides an original interpretation of these results and gives a particular role of the energy in gamma band as a survival attractor.

Selective Immunolesion of the Basal Forebrain Cholinergic Neurons: Effects on Hippocampal Activity During Sleep and Wakefulness in the Rat

Intracerebroventricular injection of the toxin 192 IgG-saporin (4μg) kills the cholinergic neurons of the basal forebrain bearing the low affinity NGF receptor (NGFr). The effect of this cholinergic denervation on the hippocampal and cortical electrical activity (EEG) was studied during sleep and wakefulness. EEG was recorded under freely-moving conditions in lesioned (n=10) and control (n=6) rats (8–16 days post-injection). In lesioned rats, active (AW) and quiet (QW) wakefulness episode durations were similar to those of controls whereas the REM sleep duration was reduced, 8 days post-lesion (P<0.01). Bouts of REM sleep were more numerous but shorter. The hippocampal theta activity was still present in lesioned-rats during AW (type 1 theta), QW (type 2 theta) and REM sleep. The frequency was unchanged but the amplitude of the three types of theta was significantly reduced (P<0.01). Type 2 theta occurred with shorter and less regular bouts (P<0.05). Abnormal slow waves (2–4 Hz) were observed during wakefulness. Histology showed a dramatic loss of NGFr-positive neurons in the basal forebrain and a decline in hippocampal and cortical acetylcholinesterase activity. These results suggest that the cholinergic septohippocampal input is not the primary pacemaker for the hippocampal theta rhythm.

Trophic-factor modulation of cortical acetylcholinesterase reappearance following transection of the medial cholinergic pathway in the adult rat

Laminar patterns of cortical acetylcholinesterase (AChE) activity are reestablished in the adult, pharmacologically unmanipulated rat following axotomy of the medial cholinergic pathway. The extent to which trophic and/or growth promoting or inhibiting agents modulate ACNE fiber reappearance is not fully understood. Such studies, however, would further clarify possible roles for these agents in neuronal plasticity in response to injury, as well as in plastic processes associated with normative functions. In the present experiments, we explored trophic modulation by intracortically infusing nerve growth factor (NGF) or somatostatin into cingulate cortex at a site distal to transection of the medial cholinergic pathway. Comparisons were made with sham-operated or noninfused transected controls, as well as with transected animals infused with renin or antibodies against NGF. Administration began 2 days after axotomy and continued at successive 3-day intervals for 4 weeks. It was found that, proximal to the lesion site, NGF increased and somatostatin decreased optical density of AChE; the number of AChE-containing fibers was unaltered compared to controls. Distal to the knife cut, both NGF and somatostatin increased number of AChE fibers but did not alter overall AChE optical density. Nonetheless, NGF produced an increase in the number of intensely staining puncta both proximal and distal to the cut. Neither renin nor anti-NGF antibodies produced statistically significant effects on optical density or number of fibers at any cortical locus studied. We conclude that NGF and somatostatin have opposite effects on the expression of AChE: whereas NGF increases AChE levels, somatostatin inhibits AChE accumulation in proximal fibers, perhaps by actions on synthesis or transport. Fiber proliferation, which only occurred distally, was affected positively by both NGF and somatostatin, indicating that neurite-promoting effects produced by both agents are confined to tissue regions where neurite extension is stimulated by axotomy. Increases in AChE-positive puncta produced by NGF, however, were not confined to regions of fiber proliferation.

Reestablishment of Laminar Patterns of Cortical Acetylcholinesterase Activity Following Axotomy of the Medial Cholinergic Pathway in the Adult Rat

Little is known about injury-induced restructuring of cholinergic neurons projecting from the basal forebrain to nonhippocampal loci in the mature mammalian brain. In an attempt to address this issue further, we made unilateral knife cuts in the cingulate cortex of adult rats and assessed the rates and extents of fiber regeneration. Among the fibers interdicted by these transections were axons of the medial cholinergic pathway, which originates prominently in the diagonal band nuclei and projects to medial frontal, cingulate, and occipital cortices. Immediately following the lesion, acetylcholinesterase (AChE)-containing fibers proximal to the transection demonstrated increased enzyme activity that remained elevated for at least 12 weeks before returning to control values within 9 months. Loss of distal cholinesterase staining was seen from 1-2 weeks postaxotomy, with partial restoration of enzyme activity within 4 weeks. By 12 weeks, virtually complete restitution of laminar patterns of AChE innervation had occurred in the cortex posterior to the knife cut. At least part of this reinnervation was attributable to fibers growing or elongating across the glial scar, with the degree of regrowth being correlated positively with the rapidity and magnitude of wound closure. Sprouting from the cut ends of axons, as well as collateral growth of those and uncut adjacent fibers, are likely sources of fibers contributing to the restoration of normal laminar profiles of AChE activity.

Cortical and striatal blood flow and acetylcholinesterase activity following lesion of the nucleus basalis magnocellularis in the rat

Cortical and striatal blood flow and acetylcholinesterase activity following lesion of the nucleus basalis magnocellularis in the rat

Cortical and striatal blood flow and acetylcholinesterase activity following lesion of the nucleus basalis magnocellularis in the rat

Cortical and striatal blood flow and acetylcholinesterase activity following lesion of the nucleus basalis magnocellularis in the rat

Neurochemical basis of dementia in Parkinson's disease.

According to their mental status, patients with Parkinson's disease can be subdivided into three groups: (1) mentally normal patients; (2) patients with severe cognitive impairment and Alzheimer-type brain pathology (neuritic plaques, neurofibrillary tangles, granulovacuolar changes); and (3) demented patients without any evidence of Alzheimer changes. Neurochemically, irrespective of the presence or absence of Alzheimer-type brain pathology, demented Parkinson patients seem to have the same disturbance of cortical cholinergic neuron function as patients with Alzheimer-type dementia (Alzheimer's disease), namely, reduced levels of cortical acetylcholine esterase and choline acetyltransferase activity. At present, the question whether the "cortical cholinergic deficiency" is the only (or sufficient) neurochemical basis for the cognitive impairment in Parkinson patients with dementia cannot be answered with certainty; the additional role of other neurotransmitter changes known to occur in the Parkinson brain, especially loss of cortical, hippocampal and subcortical noradrenaline and/or dopamine cannot be ruled out.

Reduced cholinesterase activity and somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with dementia of the Alzheimer type

Cholinesterase (ChE) activity and somatostatin-like immunoreactivity (SLI) of the cerebrospinal fluid were determined for 59 patients with dementia of the Alzheimer type (AD/SDAT) and for 19 age-matched control patients with no signs of dementia. Both ChE activities and SLI concentrations of cerebrospinal fluid were reduced significantly in dementia patients compared to the controls. In the AD/SDAT patients cholinesterase and somatostatin-like immunoreactivity levels seemed to be correlated with the severity of dementia. These findings agree with observations of reduced cortical acetylcholinesterase activities and somatostatin values in dementia of the Alzheimer type.

The activities of butyrylcholinesterase and carbonic anhydrase, the rate of anaerobic glycolysis, and the question of a constant density of glial cells in cerebral cortices of various mammalian species from mouse to whale.

Abstract— The question of a constant density of glial cells in mammalian cerebral cortex regardless of species was examined by surveying the cortical activities of two enzymes primarily localized to dial cells. The cortical activity of butyrylcholinesterase (EC 3.1.1.8) was essentially constant at a rate of approx. 0.1 μmol of butyrylthiocholine hydrolysed min‐1 g‐1 over the range of species from rat (brain wt., 1.6 g) to fin whale and sperm whale (brain wt., 6800 and 7800 g, respectively). Over the same range the activity of cortical acetylcholinesterase, a neuronal enzyme, decreases by a factor of 7. Thus, butyrylcholinesterase ranged from &lt; 2 per cent (in small rodent brains) to approximately 10 per cent (in whale brain) of the cortical acetylcholinesterase activity. The cortical activity of carbonic anhydrase (EC 4.2.1.1) was constant at a rate of 6.2 (± 0.25) μmol of CO2 evolved min‐1 g‐1 over the range of species from guinea‐pig (brain wt., 4.75 g) to fin whale (brain wt., 6800 g). These data obtained by assaying the dehydration reaction were confirmed by limited assays of the esterase activity of the enzyme (with p‐nitrophenylacetate as substrate) and agreed with limited, previously reported data for the hydration reaction. Thus, the circumstantial evidence strongly favoured a relative constancy of cortical glial cell density regardless of species.The rates of anaerobic glycolysis in the cerebral cortex of various species were also investigated. For six species from mouse (brain wt., 0.4 g) to beef (brain wt., 380 g) cortical anaerobic glycolysis varied only slightly in the range of 50–62 μmol of CO2 evolved h‐1 g‐l, whereas cortical oxygen consumption for the same range of species decreased by a factor of 3. Previously frozen samples of beef cortex glycolysed at 35 per Cent of the rate of fresh (unfrozen) samples. Since identical rates were obtained for previously frozen samples of fin whale cerebral cortex, we concluded that the relative constancy of cortical anaerobic glycolysis could be extended to the range from mouse to whale and that this aspect of cortical metabolism is probably primarily glial in localization. Some implications of the latter conclusion for the proposed role of astrocytes as modulators of neuronal activity have been discussed.

RESPIRATION AND GLYCOLYSIS OF FOCAL EPILEPTOGENIC HUMAN BRAIN TISSUE

ArticlesRESPIRATION AND GLYCOLYSIS OF FOCAL EPILEPTOGENIC HUMAN BRAIN TISSUEK. A. C. Elliott, and Wilder PenfieldK. A. C. Elliott, and Wilder PenfieldPublished Online:01 Nov 1948https://doi.org/10.1152/jn.1948.11.6.485MoreSectionsPDF (844 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByPractice Trends in the Utilization of Intraoperative Neurophysiological Monitoring in Pediatric Neurosurgery as a Function of Complication Rate, and Patient-, Surgeon-, and Procedure-Related FactorsWorld Neurosurgery, Vol. 81, No. 3-4Cerebral circulation revisited: An historical essayNeurochemical Research, Vol. 16, No. 9Adenosine: A Molecule for Synaptic Homeostasis?Ion and Energy Metabolism of the Brain at the Cellular LevelProtective effect of adenosine and nicotinamide against audiogenic seizureBiochemical Pharmacology, Vol. 23, No. 20INTERSPECIES CORRELATIONS OF CEREBRAL CORTICAL OXYGEN CONSUMPTION, ACETYLCHOLINESTERASE ACTIVITY AND CHLORIDE CONTENT: STUDIES ON THE BRAINS OF THE FIN WHALE (BAAENOPTERA PHYSALUS) AND THE SPERM WHALE (PHYSETER CATODON)Journal of Neurochemistry, Vol. 20, No. 2Amino acid content of epileptogenic human brain: Focal versus surrounding regionsBrain Research, Vol. 40, No. 2Physiopathological Mechanisms of Post-Traumatic EpilepsyEpilepsia, Vol. 11, No. 1GLYCOGEN, AMMONIA AND RELATED METABOLITES IN THE BRAIN DURING SEIZURES EVOKED BY METHIONINE SULPHOXIMINEJournal of Neurochemistry, Vol. 16, No. 2The Use of Brain SlicesThe Use of Brain SlicesEffects of convulsive doses of penicillin on the metabolism of single neuronsExperimental Neurology, Vol. 15, No. 2Cellular mechanisms in experimental epilepsy - I The effect of methionine sulfoximine on structure and function of cortical neuronsBrain Research, Vol. 1, No. 4ReferenceMaturational Changes in Cerebral Cortex III Effects of Methionine Sulfoximine on Some Electrical Parameters and Dendritic Organisation of Cortical NeuronsOn body size and tissue respirationJournal of Cellular and Comparative Physiology, Vol. 57, No. 3INTRALAMINAR DISTRIBUTION OF CYTOCHROME OXIDASE ACTIVITY IN HUMAN FRONTAL ISOCORTEXJournal of Neurochemistry, Vol. 5, No. 3EpilepsieAN ENZIMOLOGICAL STUDY ON BRAIN TISSUES OF SCHIZOPHRENIC PATIENTS. CARBOHYDRATE METABOLISM PART III. PYRUVIC ACIDPsychiatry and Clinical Neurosciences, Vol. 7, No. 3SUBSTANCES WHICH SUPPORT RESPIRATION AND METABOLIC RESPONSE TO ELECTRICAL IMPULSES IN HUMAN CEREBRAL TISSUESJournal of Neurology, Neurosurgery & Psychiatry, Vol. 16, No. 4The oxygen uptake of human cerebral cortex slices and the effects of some inhibitorsJournal of Cellular and Comparative Physiology, Vol. 40, No. 2 More from this issue > Volume 11Issue 6November 1948Pages 485-490 https://doi.org/10.1152/jn.1948.11.6.485PubMed18894653History Published online 1 November 1948 Published in print 1 November 1948 Metrics