Abstract
Purpose: To ascertain whether propofol prevents lipid peroxidation on delayed neuronal death induced by transient forebrain ischemia in the hippocampal CAI subfield in gerbils.
Methods: Forty gerbils were randomly assigned to five groups: Group I, control, sham operation treated with physiological saline solution (PSS); Group II, ischemia/reperfusion treated with PSS; Group III, ischemia/reperfusion treated with 50 mg·kg−1 propofol; Group IV, ischemia/reperfusion treated with 100 mg·kg−1 propofol; Group V, ischemia/reperfusion treated with 150 mg·kg−1 propofol. Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for four minutes under N2O/O2/halothane anesthesia after propofol or PSS. Five days later, the cerebrum was removed and each forebrain was cut into two including the hippocampus. Lipid peroxidation was determined using the production of malondialdehyde (MDA), and histopathological changes in the hippocampal CAI subfield were examined.
Results: In group II, the pyramidal cells were atrophic and pycnotic, vacuolation and structural disruption of the radial striated zone was observed. In the other four groups, these changes were not observed. Degenerative ratios of pyramidal cells were: Group I: 4.9±2.3, Group II: 94.1±4.5 (P<0.01), Group III: 12.5±5.7, Group IV: 11.0±4.6, Group V: 9.6±4.9%. Production of MDA was: Group I: 83±22, Group II: 198±25 (P<0.01), Group III: 153±39, Group IV: 113±34, Group V: 106±27 nmol·g−1 wet tissue.
Conclusion: Propofol attenuated delayed neuronal death by preventing lipid peroxidation induced by transient forebrain ischemia in the hippocampal CAI subfield in gerbils.
Résumé
Objectif: Vérfier si le propofol empêche la peroxydation lipidique qui survient à la mort neuronale différée induite par une ischémie transitoire du prosencéphale, dans le sous-champ CAI de l’hippocampe chez des gerbilles.
Méthode: On a réparti au hasard 40 gerbilles en cinq groupes: dans le groupe I, témoin, elles ont subi une opération fictive traitée avec une solution physiologique salée (SPS); dans le groupe II, une ischémie/reperfusion traitée avec une SPS; dans le groupe III, une ischémie/reperfusion traitée avec 50 mg·kg−1 de propofol; dans le groupe IV, une ischémie/reperfusion traitée avec 100 mg·kg−1 de propofol et dans le groupe V, une ischémie/reperfusion traitée avec 150 mg·kg−1 de propofol. L’ischémie transitoire du cerveau antérieur a été induite par l’occlusion bilatérale des artères carotides communes pendant quatre minutes sous anesthésie au N2O/O2/halothane après l’administration de propofol ou de SPS. Cinq minutes plus tard, le cerveau a été retiré et chaque prosencéphale a été coupé en deux, induant l’hippocampe. La peroxydation lipidique a été déterminée en utilisant la production de malondialdéhyde (MDA), et les changements histopathologiques du sous-champ CAI de l’hippocampe ont été examinés.
Résultats: Dans le groupe II, les cellules pyramidales étaient atrophiques et pycnotiques; une rupture vacuolaire et structurale de la zone radiale striée a été observée. Dans les autres groupes, ces changements n’ont pas été notés. Les taux de cellules pyramidales dégénératives ont été: groupe I: 5,8±2,5 %, groupe II: 94,1±4,5 (P<0,01), groupe III: 12,5±5,7 %, group IV: 11,0±4,6 %, groupe V: 9,4±6,6 %. La production de MDA a été dans le groupe I: 83±22, II: 198±25 (P<0,01), III: 153±39, IV: 113±34 et V: 106±27 nmol·g−1 de tissu.
Conclusion: Le propofol a réduit la mort neuronale différée en empêchant la peroxydation lipidique induite par l’ischémie transitoire du prosencéphale dans le sous-champ CAI de l’hippocampe de gerbilles.
Article PDF
Similar content being viewed by others
References
Pinaud M, Lelausque J-N, Chetanneau A, Fauchoux N, Ménégalli D, Souron R. Effects of propofol on cerebral hemodynamics and metabolism in patients with brain trauma. Anesthesiology 1990; 73: 404–9.
Kelly DF, Goodale DB, Williams J, et al. Propofol in the treatment of moderate and severe head injury: a ramdomized, prospective double-blinded pilot trial. J Neurosurg 1999; 90: 1042–52.
Sebel PS, Lowdon JD. Propofol: a new intravenous anesthetic. Anesthesiology 1989; 71: 260–77.
Vandesteene A, Trempont V, Engelman E, et al. Effect of propofol on cerebral blood flow and metabolism in man. Anaesthesia 1988; 43(Suppl): 42–3.
Van Hemelrijck J, Fitch W, Mattheussen M, Van Aken H, Plets C, Lauwers T. Effect of propofol on cerebral circulation and autoregulation in the baboon. Anesth Analg 1990; 71: 49–54.
Ravussin P, Guinard JP, Ralley F, Thorin D. Effect of propofol on cerebrospinal fluid pressure and cerebral perfusion pressure in patients undergoing craniotomy. Anaesthesia 1988; 43(Suppl): 37–41.
Kochs E, Hoffman WE, Werner C, Thomas C, Albrecht RF, Schulte am Esch J. The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology 1992; 76: 245–52.
Arcadi FA, Rapisarda A, De Luca R, Trimarchi GR, Costa G Effect of 2,6-diisopropylphenol on the delayed hippocampal cell loss following transient forebrain ischemia in the gerbil. Life Sci 1996; 58: 961–70.
Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 1982; 239: 57–69.
Yamaguchi S, Midorikawa Y, Okuda Y, Kitajima T. Propofol prevents delayed neuronal death following transient forebrain ischemia in gerbils. Can J Anesth 1999; 46: 593–8.
Todd M, Warner DS. A comfortable hypothesis reevaluated. Cerebral metabolic depression and brain protection during eschemia (Editorial). Anesthesiology 1992; 76: 161–4.
Sitar SM, Hanifi-Moghaddam P, Gelb A, Cechetto DF, Siushansian R, Wilson JX. Propofol prevents peroxide-induced inhibition of glutamate transport in cultured astrocytes. Anesthesiology 1999; 90: 1446–53.
Ansley DM, Sun J, Visser WA, et al. High dose propofol enhances red cell antioxidant capacity during CPB in humans. Can J Anesth 1999; 46: 641–8.
Ansley DM, Lee J, Godin DV, Garnett ME, Qayumi AK. Propofol enhances red cell antioxidant capacity in swine and humans. Can J Anaesth 1998; 45: 233–9.
Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG. The antioxidant potential of propofol (2,6-diisoprophylphenol). Br J Anaesth 1992; 68: 613–8.
Hans P, Deby-Dupont G, Deby C, et al. Increase in antioxidant capacity of plasma during propofol anesthesia. J Neurosurg Anesth 1997; 9: 234–6.
Hans P, Deby C, Deby-Dupont G, Vrijens B, Albert A, Lamy M. Effect of propofol on in vitro lipid peroxidation induced by difference free radical generating systems: a comparison with vitamin E. J Neurosurg Anesth 1996; 8: 154–8.
Mouithys-Mickalad A, Hans P, Deby-Dupont G, Hoebeke M, Deby C, Lamy M. Propofol reacts with peroxynitrite to form a phenoxyl radical: demonstration by electron spin resonance. Biochem Biophy Res Com 1998; 249: 833–7.
De La Cruz JP, Zanca A, Carmona JA, Sánchez de la Cuesta F. The effect of propofol on oxidative stress in platelets from surgical patients. Anesth Analg 1999; 89: 1050–5.
De La Cruz JP, Sedeño G, Carmona JA, Sánchez de la Cuesta F. Thein vitro effects of propofol on tissular oxidative stress in the rat. Anesth Analg 1998; 87: 1141–6.
De La Cruz JP, Villalobos MA, Sedeño G, Sánchez de la Cuesta F. Effect of propofol on oxidative stress in an in vitro model of anoxia-reoxygenation in the rat brain. Brain Res 1998; 800: 136–44.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351–8.
Petito CK, Feldmann E, Pulsinelli WA, Plum F. Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 1987; 37: 1281–6.
Horn M, Schlote W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol 1992; 85: 79–87.
Maeda M, Sugiyama T, Akai F, Jikihara I, Hayashi Y, Takagi H Single stranded DNA as an immunocytochemical marker for apoptotic change of ischemia in the gerbil hippocampus. Neurosci Lett 1998; 240: 69–72.
Kinoshita M, Tomimoto H, Kinoshita A, Kumar S, Noda M. Up-regulation of theNedd2 gene encoding an ICE/Ced-3-like cysteine protease in the gerbil brain after transient global ischemia. J Cereb Blood Flow Metab 1997; 17: 507–14.
Nitatoir T, Sato N, Waguri S, et al. Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 1995; 15: 1001–11.
Kihara S, Shiraishi T, Nakagawa S, Toda K, Tahuchi K. Visualization of DNA double strand breaks in the gerbil hippocampal CAl following transient ischemia. Neurosci Lett 1994; 175: 133–6.
Yamaguchi S, Ogata H, Hamaguchi S, Kitajima T. Superoxide radical generation and histopathological changes in hippocampal Cal after ischaemia/reperfusion in gerbils. Can J Anaesth 1998; 45: 226–32.
Hall ED. Free radicals and CNS injury. Crit Care Clin 1989; 5: 793–805.
Ikeda Y, Long DM. The molecular basis of brain injury and brain edema: the role of oxygen free radicals. Neurosurgery 1990; 27: 1–11.
Siesjö BK, Agardh C-D, Bengtsson F. Free radicals and brain damage. Cerebrovascular and Brain Metabolism Reviews 1989; 1: 165–211.
Siesjö BK. Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. J Neurosurg 1992; 77: 337–54.
Hara H, Kato H, Kogure K. Protective effect of α-tocopherol on ischemic neuronal damage in the gerbil hippocampus. Brain Res 1990; 510: 335–8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamaguchi, S., Hamaguchi, S., Mishio, M. et al. Propofol prevents lipid peroxidation following transient forebrain ischemia in gerbils. Can J Anesth 47, 1025–1030 (2000). https://doi.org/10.1007/BF03024877
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03024877