Abstract
Neurosurgical procedures are associated with unintentional damage to the brain during surgery, known as surgically induced brain injuries (SBI), which have been implicated in orchestrating structural and neurobehavioral deterioration. Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population. Sprague-Dawley rats were treated with low- and high-dose propofol 30 min before SBI. At 24 h post injury, brain water content and neurobehavioral assessment was conducted based on previously established models. In vehicle-treated rats, SBI resulted in significant cerebral edema and higher neurological deficit scores compared with sham-operated rats. Low- or high-dose propofol therapy neither reduced cerebral edema nor improved neurologic function. The results suggest that propofol pretreatment fails to provide neuroprotection in SBI rats. However, it is possible that a SBI model with less magnitude of injury or that propofol re-dosing, given the short-acting pharmacokinetic property of propofol, may be needed to provide definitive conclusions.
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References
Adembri C, Venturi L, Tani A, Chiarugi A, Gramigni E, Cozzi A, Pancani T, De Gaudio RA, Pellegrini-Giampietro DE (2006) Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism. Anesthesiology 104:80–89
Andrews RJ, Muto RP (1992) Retraction brain ischaemia: cerebral blood flow, evoked potentials, hypotension and hyperventilation in a new animal model. Neurol Res 14:12–18
Arcadi FA, Rapisarda A, De Luca R, Trimarchi GR, Costa G (1996) Effect of 2,6-diisopropylphenol on the delayed hippocampal cell loss following transient forebrain ischemia in the gerbil. Life Sci 58:961–970
Bilotta F, Gelb AW, Stazi E, Titi L, Paoloni FP, Rosa G (2013) Pharmacological perioperative brain neuroprotection: a qualitative review of randomized clinical trials. Br J Anaesth 110(Suppl 1):i113–i120
Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–634
Hernesniemi J, Leivo S (1996) Management outcome in third ventricular colloid cysts in a defined population: a series of 40 patients treated mainly by transcallosal microsurgery. Surg Neurol 45:2–14
Hsing CH, Lin MC, Choi PC, Huang WC, Kai JI, Tsai CC, Cheng YL, Hsieh CY, Wang CY, Chang YP, Chen YH, Chen CL, Lin CF (2011) Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKbeta/NF-kappaB signaling. PLoS One 6:e17598
Hsu BG, Yang FL, Lee RP, Peng TC, Chen HI (2005) Effects of post-treatment with low-dose propofol on inflammatory responses to lipopolysaccharide-induced shock in conscious rats. Clin Exp Pharmacol Physiol 32:24–29
Ito H, Watanabe Y, Isshiki A, Uchino H (1999) Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 43:153–162
Jadhav V, Solaroglu I, Obenaus A, Zhang JH (2007) Neuroprotection against surgically induced brain injury. Surg Neurol 67:15–20
Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H (2008) The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther 14:95–106
Lee JH, Cui HS, Shin SK, Kim JM, Kim SY, Lee JE, Koo BN (2013) Effect of propofol post-treatment on blood–brain barrier integrity and cerebral edema after transient cerebral ischemia in rats. Neurochem Res 38:2276–2286
Lekic T, Ani C (2012) Posterior circulation stroke: animal models and mechanism of disease. J Biomed Biotechnol 2012:587590
Luo T, Wu J, Kabadi SV, Sabirzhanov B, Guanciale K, Hanscom M, Faden J, Cardiff K, Bengson CJ, Faden AI (2013) Propofol limits microglial activation after experimental brain trauma through inhibition of nicotinamide adenine dinucleotide phosphate oxidase. Anesthesiology 119:1370–1388
Schallert T, Upchurch M, Lobaugh N, Farrar SB, Spirduso WW, Gilliam P, Vaughn D, Wilcox RE (1982) Tactile extinction: distinguishing between sensorimotor and motor asymmetries in rats with unilateral nigrostriatal damage. Pharmacol Biochem Behav 16:455–462
Sulejczak D, Grieb P, Walski M, Frontczak-Baniewicz M (2008) Apoptotic death of cortical neurons following surgical brain injury. Folia Neuropathol 46:213–219
Yamaguchi M, Jadhav V, Obenaus A, Colohan A, Zhang JH (2007) Matrix metalloproteinase inhibition attenuates brain edema in an in vivo model of surgically-induced brain injury. Neurosurgery 61:1067–1075
Yamaguchi S, Hamaguchi S, Mishio M, Okuda Y, Kitajima T (2000) Propofol prevents lipid peroxidation following transient forebrain ischemia in gerbils. Can J Anaesth 47:1025–1030
Zhou R, Yang Z, Tang X, Tan Y, Wu X, Liu F (2013) Propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines in a rat model of experimental stroke. PLoS One 8:e82729
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This study is partially supported by National Institutes of Health grant NS084921.
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Pakkianathan, C. et al. (2016). Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model. In: Applegate, R., Chen, G., Feng, H., Zhang, J. (eds) Brain Edema XVI. Acta Neurochirurgica Supplement, vol 121. Springer, Cham. https://doi.org/10.1007/978-3-319-18497-5_56
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DOI: https://doi.org/10.1007/978-3-319-18497-5_56
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