Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-13T05:15:08.621Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of repeated anaesthesia on central cholinergic function in the rat cerebral cortex

Published online by Cambridge University Press:  02 June 2005

C. D. Hanning ,
A. Blokland ,
M. Johnson  and
E. K. Perry
C. D. Hanning
Affiliation:
Leicester General Hospital, Department of Anaesthesia, Leicester, UK
A. Blokland
Affiliation:
Maastricht Brain & Behavior Institute, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands
M. Johnson
Affiliation:
Centre for Development in Clinical Brain Ageing, MRC Building, Newcastle General Hospital, Newcastle upon Tyne, UK
E. K. Perry
Affiliation:
Centre for Development in Clinical Brain Ageing, MRC Building, Newcastle General Hospital, Newcastle upon Tyne, UK
Get access

Abstract

Summary

Background and objective: General anaesthesia may contribute to postoperative cognitive decline in the elderly. The aim was to determine the effects of repeated pentobarbital anaesthesia throughout life on central cholinergic function in the rat.

Methods: Young Lewis rats were randomly allocated to two groups. The anaesthesia group (n = 15) was anaesthetized with pentobarbital 20 mg kg−1 intraperitoneally at 6, 8.5, 11, 13.5, 16, 18.5, 21 and 23.5 months of age. The control group (n = 12) was treated identically, apart from the anaesthesia. At 26 months of age, the animals were killed and the brain dissected and stored for analysis. Central cholinergic function in the cortex and hippocampus was assessed by measuring [3H]-epibatidine and [125I]α-bungarotoxin binding to nicotinic receptors and choline acetyltransferase (ChAT) activity.

Results: Tissue from nine rats in the anaesthesia group and eight in the control group was available for analysis. There was a significant reduction in α-bungarotoxin binding in the anaesthetized compared with the control group in the superior cortex (P < 0.0002) and molecular cortex (P < 0.04). There were no significant differences between the groups for epibatidine binding or ChAT.

Conclusions: Repeated anaesthesia in rat reduces central nicotinic cholinergic binding in the cortex. The findings may have implications for postoperative cognitive function studies.

Keywords

ANAESTHETICS, GENERALMEMORY DISORDERSRECEPTORS, NEUROTRANSMITTER, receptors, cholinergic, nicotinic
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 2 , February 2003 , pp. 93 - 97
Copyright
2003 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Houx PJ, Vreeling FW, Jolles J. Rigorous health screening reduces age effect on memory scanning task. Brain Cognit 1991; 15: 246–260.Google Scholar
Houx PJ, Jolles J. Age-related decline of psychomotor speed: effects of age, brain health, sex, and education. Percept Motor Skills 1993; 76: 195–211.Google Scholar
Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. Lancet 1998; 351: 857–861.Google Scholar
Abildstrom H, Rasmussen LS, Rentowl P, et al. Cognitive dysfunction 1–2 after non-cardiac surgery in the elderly. Acta Anaesth Scand 2000; 44: 1246–1251.Google Scholar
Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. New Engl J Med 2001; 344: 395–402.Google Scholar
Robson MJ, Alston RP, Deary IJ, Andrews RP, Souter MJ, Yates S. Cognition after coronary artery surgery is not related to postoperative jugular bulb oxyhemoglobin desaturation. Anesth Analg 2000; 91: 1317–1326.Google Scholar
O'Brien JT. The ‘glucocorticoid cascade’ hypothesis in man – prolonged stress may cause permanent brain damage. Br J Psych 1997; 170: 199–201.Google Scholar
Lupien SJ, de Leon M, de Santi S, et al. Cortisol concentrations during human ageing predict hippocampal atrophy and memory deficits. Nat Neurosci 1998; 1: 69–73.Google Scholar
Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele E4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467–1472.Google Scholar
Tiraboschi P, Hansen LA, Alford M, et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology 2000; 54: 407–411.Google Scholar
Levy ML, Cummings JL, Kahn-Rose R. Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology 1999; 45 (Suppl 1): 15–22.Google Scholar
Ebert U, Kirch W. Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest 1998; 28: 944–949.Google Scholar
Blokland A, Honig W, Jolles J. Long-term consequences of repeated anaesthesia on reaction time performance in ageing rats. Br J Anaesth 2001; 87: 781–783.Google Scholar
Nordberg A. Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications. Biol Psychiatry 2001; 49: 200–210.Google Scholar
Perry EK, Lee MLW, Martin-Ruiz CM, et al. Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psych 2001; 158: 1058–1066.Google Scholar
Court YA, Perry EK, Griffiths M, et al. Cholinergic nicotinic and muscarinic receptor binding in the developing and ageing human hippocampus. Brain Res Dev Brain Res 1997; 101: 93–105.Google Scholar
Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE. Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J Neurol Sci 1977; 34: 247–265.Google Scholar
Tonner PH, Miller KW. Molecular sites of general anaesthetic action on acetylcholine receptors. Eur J Anaesthesiol 1995; 12: 21–30.Google Scholar
Dilger JP, Boguslavsky R, Barann M, Katz T, Vidal AM. Mechanisms of barbiturate inhibition of acetylcholine receptor channels. J Gen Physiol 1997; 109: 401–414.Google Scholar
Watanabe I, Andoh T, Furuya R, Sasaki T, Kamiya Y, Itoh H. Depressant and convulsant barbiturates both inhibit neuronal nicotinic acetylcholine receptors. Anesth Analg 1999; 88: 1406–1411.Google Scholar
Downie DL, Franks NP, Lieb WR. Effects of thiopental and its optical isomers on nicotinic acetylcholine receptors. Anesthesiology 2000; 93: 774–783.Google Scholar