Delayed combination therapy of local brain hypothermia and decompressive craniectomy on acute stroke outcome in rat

Document Type : Original Article

Authors

1 Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

2 Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Neurology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Abstract

Objective(s):Hypothermia and decompressive craniectomy (DC) have been shown to be neuroprotective. This study was designed to evaluate neuroprotective effects of delayed singular or combination of DC and local hypothermia on stroke.
Materials and Methods: Cerebral ischemia was induced in 48 Wistar rats assigned to 4 groups: control, decompressive craniectomy (DC), local hypothermia (LH), combination of hypothermia and craniectomy (HC). Infarct size and BBB disruption were measured 48 hr after ischemia insult. Neurological deficits were assessed at 24 and 48 hr after stroke by using sticky tape test, hanging-wire test and Bederson’s scoring system. BBB disruption was measured by Evans blue dye leakage.
Results: Although infarct size was significantly reduced in LH, DC and HC groups (P<0.001), combination therapy was more neuroprotective compared to craniectomy alone (P<0.01). BBB disruption was significantly reduced in DC (P< 0.05) and LH and HC (P< 0.01).While sticky tape test (PPP<0.05) showed better behavioral performance only in HC, Bederson test showed improved behavioral functions of both LH (PPP<0.01). Neurological deficits were also decreased in LH (P<0.05) or HC (PPConclusion: Based on our data, although both delayed local hypothermia and craniectomy are protective after stoke, combination therapy of them is more neuroprotective than given alone.

Keywords

References

1. Allahtavakoli M, Shabanzadeh AP, Sadr SS, Parviz M, Djahanguiri B. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma ligand, reduces infarction volume and neurological deficits in an embolic model of stroke. Clin Exp Pharmacol Physiol 2006; 33:1052-1058.
2. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998; 352:1245-1251.
3. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333:1581-1588.
4. Hamann GF, Burggraf D, Martens HK, Liebetrau M, Jager G, Wunderlich N, et al. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke 2004; 35:764-769.
5. Kollmar R, Blank T, Han JL, Georgiadis D, Schwab S. Different degrees of hypothermia after experimental stroke: short- and long-term outcome. Stroke 2007; 38:1585-1589.
6. Saini M, Saqqur M, Kamruzzaman A, Lees KR, Shuaib A. Effect of hyperthermia on prognosis after acute ischemic stroke. Stroke 2009; 40:3051-3059.
7. Colbourne F, Sutherland G, Corbett D. Postischemic hypothermia. A critical appraisal with implications for clinical treatment. Mol Neurobiol 1997; 14:171-201.
8. Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998; 29:2461-2466.
9. Lyden TMHaPD. Hypothermia after acute ischemic stroke.” J Neurotrauma 2009; 26:387-391.
10. van der Worp HB, Macleod MRM, Kollmar R. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials. J Cereb Blood Flow Metab 2010; 30:1079-1093.
11. Hemmen MAYaTM. Therapeutic hypothermia for brain ischemia: where have we come and where do we go? Stroke 2010; 41:S72-S74.
12. Karibe H, Zarow GJ, Graham SH, Weinstein PR. Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1994; 14:620-627.
13. Doerfler A, Forsting M, Reith W, Staff C, Heiland S, Schabitz WR, et al. Decompressive craniectomy in a rat model of "malignant" cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach. J Neurosurg 1996; 85:853-859.
14. Forsting M, Reith W, Schabitz WR, Heiland S, von Kummer R, Hacke W, et al. Decompressive craniectomy for cerebral infarction. An experimental study in rats. Stroke 1995; 26:259-264.
15. Flechsenhar J, Woitzik J, Zweckberger K, Amiri H, Hacke W, Juttler E. Hemicraniectomy in the management of space-occupying ischemic stroke. J Clin Neurosci 2013; 20:6-12.
16. Els T, Oehm E, Voigt S, Klisch J, Hetzel A, Kassubek J. Safety and therapeutical benefit of hemicraniectomy combined with mild hypothermia in comparison with hemicraniectomy alone in patients with malignant ischemic stroke. Cerebrovasc Dis 2006; 21:79-85.
17. Delashaw JB, Broaddus WC, Kassell NF, Haley EC, Pendleton GA, Vollmer DG, et al. Treatment of right hemispheric cerebral infarction by hemicraniectomy. Stroke 1990; 21:874-881.
18. Foerch C, Lang JM, Krause J, Raabe A, Sitzer M, Seifert V, et al. Functional impairment, disability, and quality of life outcome after decompressive hemicraniectomy in malignant middle cerebral artery infarction. J Neurosurg 2004; 101:248-254.
19. Vahedi K, Vicaut E, Mateo J, Kurtz A, Orabi M, Guichard JP, et al. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke 2007; 38:2506-2517.
20. Doerfler A, Schwab S, Hoffmann TT, Engelhorn T, Forsting M. Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats. Stroke 2001; 32:2675-2681.
21. Nagel S, Su Y, Horstmann S, Heiland S, Gardner H, Koziol J, et al. Minocycline and hypothermia for reperfusion injury after focal cerebral ischemia in the rat: effects on BBB breakdown and MMP expression in the acute and subacute phase. Brain Res 2008; 1188:198-206.
22. Schwartz AE, Finck AD, Stone JG, Connolly ES, Edwards NM, Mongero L. Delayed selective cerebral hypothermia decreases infarct volume after reperfused stroke in baboons. J Neurosurg Anesthesiol 2011; 23:124-130.
23. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20:84-91.
24. Onesti ST, Baker CJ, Sun PP, Solomon RA. Transient hypothermia reduces focal ischemic brain injury in the rat. Neurosurgery 1991; 29:369-373.
25.  Allahtavakoli RM, Arababadi NK, Shamsizadeh A, Javanmardi K. Delayed post ischemic treatment with Rosiglitazone attenuates infarct volume, neurological deficits and neutrophilia after embolic stroke in rat. Brain Res 2009; 1271:121–127.
26. Rezazadeh H, Hoseini Kahnuee M, Roohbakhsh A, Shamsizadeh A, Rahmani MR, Bidaki R, et al. Neuroprotective consequences of postconditioning on embolic model of cerebral ischemia in rat. Iran J Basic Med Sci 2013; 16:144-149.
27. Whishaw IQ, Kolb B. The Behavior of the Laboratory Rat. 1st Ed. New York: Oxford University Press; 2005. 
28. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986; 17:472-476.
29. Prinz V, Laufs U, Gertz K, Kronenberg G, Balkaya M, Leithner C, et al. Intravenous rosuvastatin for acute stroke treatment: an animal study. Stroke 2008; 39:433-438.
30. Awad AS. Role of AT1 receptors in permeability of the blood-brain barrier in diabetic hypertensive rats. Vascul Pharmacol 2006; 45:141-147.
31. Mohammadi MT, Shid-Moosavi SM, Dehghani GA. Contribution of nitric oxide synthase (NOS) in blood-brain barrier disruption during acute focal cerebral ischemia in normal rat. Pathophysiology 2012; 19: 13-20. 
32. Cho DY, Chen TC, Lee HC. Ultra-early decompressive craniectomy for malignant middle cerebral artery infarction. Surg Neurol 2003; 60:227-232.
33. Clark DL, Colbourne F. A simple method to induce focal brain hypothermia in rats. J Cereb Blood Flow Metab 2007; 27:115-122.
34. Kollmar R, Schabitz WR, Heiland S, Georgiadis D, Schellinger PD, Bardutzky J, et al. Neuroprotective effect of delayed moderate hypothermia after focal
cerebral ischemia: an MRI study. Stroke 2002; 33:1899-1904.
35. Baker CJ, Fiore AJ, Frazzini VI, Choudhri TF, Zubay GP, Solomon RA. Intraischemic hypothermia decreases the release of glutamate in the cores of permanent focal cerebral infarcts. Neurosurgery 1995; 36:994-1001.
36. Ji X, Luo Y, Ling F, Stetler RA, Lan J, Cao G, et al. Mild hypothermia diminishes oxidative DNA damage and pro-death signaling events after cerebral ischemia: a mechanism for neuroprotection. Front Biosci 2007; 12:1737-1747.
37. Burk J, Burggraf D, Vosko M, Dichgans M, Hamann GF. Protection of cerebral microvasculature after moderate hypothermia following experimental focal cerebral ischemia in mice. Brain Res 2008; 1226:248-255.
38. Ohta H, Terao Y, Shintani Y, Kiyota Y. Therapeutic time window of post-ischemic mild hypothermia and the gene expression associated with the neuroprotection in rat focal cerebral ischemia. Neurosci Res 2007; 57:424-433.
39. Goto Y, Kassell NF, Hiramatsu K, Soleau SW, Lee KS. Effects of intraischemic hypothermia on cerebral damage in a model of reversible focal ischemia. Neurosurgery 1993; 32:980-984.
40. Ji Y, Wu Y, Ji Z, Song W, Xu S, Wang Y, et al. [Comparison of neuroprotective effects of hypothermia induced by different methods in rats with early cerebral ischemia]. Nan Fang Yi Ke Da Xue Xue Bao 2012; 32:89-92.
41. Campbell K, Meloni BP, Knuckey NW. Combined magnesium and mild hypothermia (35 degrees C) treatment reduces infarct volumes after permanent middle cerebral artery occlusion in the rat at 2 and 4, but not 6 h. Brain Res 2008; 1230:258-264.
42. Sahin S, Alkan T, Temel SG, Tureyen K, Tolunay S, Korfali E. Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats. J Clin Neurosci 2010; 17:227-231.
43. Jieyong B, Zhong W, Shiming Z, Dai Z, Kato Y, Kanno T, et al. Decompressive craniectomy and mild hypothermia reduces infarction size and counterregulates Bax and Bcl-2 expression after permanent focal ischemia in rats. Neurosurg Rev 2006; 29:168-172.

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