Summary
We evaluated the effects of a novel pharmacological brain cooling (PBC) method with indomethacin (IND), a nonselective cyclooxygenase inhibitor, without the use of cooling blankets in patients with hemorrhagic stroke. Forty-six patients with hemorrhagic stroke (subarachnoid hemorrhage; n = 35, intracerebral hemorrhage; n = 11) were enrolled in this study.
Brain temperature was measured directly with a temperature sensor. Patients were cooled by administering transrectal IND (100 mg) and a modified nasopharyngeal cooling method (positive selective brain cooling) initially. Brain temperature was controlled with IND 6 mg/kg/day for 14 days. Cerebrospinal fluid concentrations of interleukin-1β (CSF IL-1β) and serum bilirubin levels were measured at 1, 2, 4, and 7 days. The incidence of complicating symptomatic vasospasm after subarachnoid hemorrhage was lower than in non- PBC patients. CSF IL-1β and serum bilirubin levels were suppressed in treated patients.
IND has several beneficial effects on damaged brain tissues (anticytokine, free radical scavenger, antiprostaglandin effects, etc.) and prevents initial and secondary brain damage. PBC treatment for hemorrhagic stroke in patients appears to yield favorable results by acting as an antiinflammatory cytokine and reducing oxidative stress.
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References
Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 99: 13926–13931
Clifton GL, Jiang JY, Lyeth BG, Jenkins LW, Hamm RJ, Hayes RL (1991) Marked protection by moderate hypothermia after experimental traumatic brain injury. J Cereb Blood Flow Metab 11: 114–121
Dohi K, Jimbo H, Ikeda Y (2000) Usefulness of continuous brain temperature monitoring after SAH. Jpn J Crit Care Med 12: 103–104
Dohi K, Mochizuki Y, Satoh K, Jimbo H, Hayashi M, Toyoda I, Ikeda Y, Abe T, Aruga T (2003) Transient elevation of serum bilirubin (a heme oxygenase-1 metabolite) level in hemorrhagic stroke: bilirubin is a marker of oxidant stress. Acta Neurochir [Suppl] 86: 247–249
Dohi K, Jimbo H, Abe T, Aruga T (2005) A novel and simple selective brain cooling method by nasopharyngeal cooling (positive selective brain cooling method). Acta Neurochir [Suppl] [in press]
Harrigan MR, Tuteja S, Neudeck BL (1997) Indomethacin in the management of elevated intracranial pressure: a review. J Neurotrauma 14: 637–650
Ikeda Y, Matsumoto K, Dohi K, Jimbo H, Sasaki K, Satoh K (2001) Direct superoxide scavenging activity of nonsteroidal anti-inflammatory drugs: determination by electron spin resonance using the spin trap method. Headache 41: 138–141
Imaizumi Y, Mizushima H, Matsumoto H, Dohi K, Matsumoto Ki, Ohtaki H, Funahashi H, Matsunaga S, Horai R, Asano M, Iwakura Y, Shioda S (2001) Increased expression of interleukin-1β in mouse hippocampus after global cerebral ischemia. Acta Histochem Cytochem 34: 357–362
Kondo F, Kondo Y, Gomez-Vargas M, Ogawa N (1998) Indomethacin inhibits delayed DNA fragmentation of hippocampal CA1 pyramidal neurons after transient forebrain ischemia in gerbils. Brain Res 791: 352–356
Marion DW, Obrist WD, Carlier PM, Penrod LE, Darby JM (1993) The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report. J Neurosurg 79: 354–362
Mizushima H, Zhou CJ, Dohi K, Horai R, Asano M, Iwakura Y, Hirabayashi T, Arata S, Nakajo S, Takaki A, Ohtaki H, Shioda S (2002) Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1. J Comp Neurol 448: 203–216
Nagasaka T, Brinnel H, Hales JR, Ogawa T (1998) Selective brain cooling in hyperthermia: the mechanisms and medical implications. Med Hypotheses 50: 203–211
Nakagawa K, Hirai K, Aoyagi M, Yamamoto K, Hirakawa K, Katayama Y (2000) Bloody cerebrospinal fluid from patients with subarachnoid hemorrhage alters intracellular calcium regulation in cultured human vascular endothelial cells. Neurol Res 22: 588–596
Ohtaki H, Yin L, Nakamachi T, Dohi K, Kudo Y, Makino R, Shioda S (2004) Expression of tumor necrosis factor alpha in nerve fibers and oligodendrocytes after transient focal ischemia in mice. Neurosci Lett 368: 162–166
Osuka K, Suzuki Y, Watanabe Y, Takayasu M, Yoshida J (1998) Inducible cyclooxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 29: 1219–1222
Shiozaki T, Sugimoto H, Taneda M, Yoshida H, Iwai A, Yoshioka T, Sugimoto T (1993) Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. J Neurosurg 79: 363–368
Sminia P, Haveman J, Ongerboer de Visser BW (1989) What is a safe heat dose which can be applied to normal brain tissue? Int J Hyperthermia 5: 115–117
Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235: 1043–1046
Tomaro ML, Batlle AM (2002) Bilirubin: its role in cytoprotection against oxidative stress. Int J Biochem Cell Biol 34: 216–220
Watanabe T, Morimoto A, Murakami N (1991) ACTH response in rats during biphasic fever induced by interleukin-1. Am J Physiol 261: R1104–1108
Yin L, Ohtaki H, Nakamachi T, Dohi K, Iwai Y, Funahashi H, Makino R, Shioda S (2003) Expression of tumor necrosis factor alpha (TNFalpha) following transient cerebral ischemia. Acta Neurochir [Suppl] 86: 93–96
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Dohi, K. et al. (2006). Pharmacological brain cooling with indomethacin in acute hemorrhagic stroke: antiinflammatory cytokines and antioxidative effects. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_14
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DOI: https://doi.org/10.1007/3-211-30714-1_14
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