Effects of ketamine-midazolam anesthesia on focal cerebral ischemic injury in rats

Abstract

Abstract: Objective To compare the effects of anesthesia with ketamine and ketamine-midazolam on focal cerebral ischemic injury in rats and evaluate the neuroprotective effect of ketamine-midazolam anesthesia during surgical procedures. Methods Thirty male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) under anesthesia with intraperitoneal administration of ketamine alone or in combination with midazolam (n=15). Neurological scoring was conducted the infarct size measured at 4 h and 24 h after the surgery. Histological examination was performed using TUNEL staining 72 h after MCAO. Results After MCAO, the neurological scores showed no significant difference between ketamine and ketamine-midazolam groups (1.57±0.65 vs 1.74±0.52, P>0.05), but the rats in the latter group had significantly smaller infarct size (38.48%±4.18% vs 24.1%±4.63%, P<0.05) and lower apoptotic cell density (258±15 cells/mm² vs 178±23 cells/mm², P<0.05) in the penumbra. Conclusion Compared with ketamine used alone, anesthesia with the combination of ketamine and midazolam may provide neuroprotection from ischemic cerebral injury by reducing the infarct size and lowering the cell apoptosis rate following MCAO in rats.

CLC Number:

ZHANG Peng-bo^1,2, LIU Yong¹, LI Jie¹, CHEN Xin-lin¹, TIAN Ying-fang¹, SUN Jian-jun¹, LIU Jian-xin¹. Effects of ketamine-midazolam anesthesia on focal cerebral ischemic injury in rats[J]. Journal of Southern Medical University, 2004, 24(12): 1337-1341.

References

[1] Fitzal S. Ketamine and neuroprotection. Clinical outlook[J]. Anaesthesist, 1997, 46(Suppl 1): S65-S70.
[2] Mortier E, Struys M, Herregods L. Therapeutic coma or neuroprotection by anaesthetics[J]. Acta Neurol Belg, 2000, 100(4): 225-8.
[3] Chen L, Gong Q, Xiao C, et al. Effects ofpropofol, midazolam and thiopental sodium on outcome and amino acids accumulation in focal cerebral ischemia-reperfusion in rats [J]. Chin Med J (Engl),2003, 116(2): 292-6.
[4] Sakai F, Amaha K. Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter [J]. Can J Anaesth,2000, 47(8): 800-6.
[5] Porro CA, CavazzutiM, GiulianiD, et al. Effects ofketamine anesthesia on central nociceptive processing in .the rat: A 2-deoxyglucose study[J]. Neuroscience, 2004, 125(2): 485-94.
[6] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke, 1989, 20(1): 84-91.
[7] Wang CX, Yang Y, Yang T, et al. A focal embolic model of cerebral ischemia in rats: introduction and evaluation [J]. Brain Res Brain Res Protoc, 2001, 7(2): 115-20.
[8] Yang Y, Yang T, Li Q, et al. A new reproducible focal cerebral ischemia model by introduction of polyvinylsiloxane into the middle cerebral artery: a comparison study[J]. J Neurosci Methods,2002, 118(2): 199-206.
[9] Sobrado M, Lopez MG, Carceller F, et al. Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia [J]. Neuroscience, 2003,118(1): 107-13.
[10] Zhang RL, Zhang L, Zhang ZG, etal. Migration and differentiation of adult rat subventricular zone progenitor cells transplanted into the adult rat striatum[J]. Neuroscience, 2003, 116(2): 373-82.
[11] Reglodi D, Tamás A, Lengvári I. Examination of sensorimotor performance following middle cerebral artery occlusion in rats [J].Brain Res Bull, 2003, 59(6): 459-66.
[12] Gill R, Sibson NR, Hatfield RH, et al. A comparison of the early development of ischaemic damage following permanent middle cerebral artery occlusion in rats as assessed using magnetic resonance imaging and histology [J]. J Cereb Blood Flow Metab,1995, 15(1): 1-11.
[13] Li Y, Powers C, Jiang N, et al. Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in the rat [J]. J Neurol Sci, 1998,156(2): 119-32.
[14] Engelhard K, Werner C, Eberspacher E, et al. The effect of the alpha 2- agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S (+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats[J]. Anesth Analg, 2003, 96(2): 524-31.
[15] Goto Y, O’Malley C, Fanning NF, et al. Benzodiazepines inhibit the rate ofneutrophil apoptosis[J]. Ir J Med Sci, 2003, 172(4): 191-4.
[16] Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents cause widespread neurodegeneration in the developing rat brain and persistent learning deficits [J]. J Neurosci, 2003, 23(3): 876-82.
[17] Proescholdt M, Heimann A, Kempski O. Neuroprotection of S(+) ketamine isomer in global forebrain ischemia [J]. Brain Res, 2001,904(2): 245-51.
[18] Lazar RM, Fitzsimmous BF, Masrshall RS, et al. Midazolam challenge reinduces neurological deficits after transient ischemic attack[J]. Stroke, 2003, 34(3): 794-6.
[19] Sugawara T, Kawase M, Lewen A, et al. Effect ofhypotension severity on hippocampal CA1 neurons in a rat global ischemia model[J]. Brain Res, 2000, 877(2): 281-7.
[20] Zausinger S, Hungerhuber E, Baethmann A, et al. Neurological impairment in rats after transient middle cerebral artery occlusion: a comparative study under various treatment paradigms [J]. Brain Res, 2000, 863(1-2): 94-105.