Modification of the method of thread manufacture improves stroke induction rate and reduces mortality after thread-occlusion of the middle cerebral artery in young or aged rats

Improving models of human stroke by the use of aged animals has been advocated; however the commonly used rat middle cerebral artery thread-occlusion model has produced suboptimal stroke induction and excess mortality in aged rats. We report the development of a modified method for silicone-coating the tip of occluding threads which produces a malleable silicone-coated tip which is firmly bonded and of highly consistent diameter, and overcomes problems of thread insertion through the narrowed carotid canal found in aged animals. Comparison of stroke outcomes and mortality were made between these threads and heat-treated poly-L-lysine coated threads. The rate of successful stroke induction in aged rats was significantly improved (from 14% to 86%). Similarly, mortality fell from 21-31% to 3-7% or less in both young and old rats with or without diabetes and hypertension. An occluding thread tip diameter of 0.35-0.38 mm was optimal for induction of mid-sized strokes in both young and old rats. This method of thread manufacture overcomes problems of inconsistency of diameter and bonding of the silicone-coated tip, and these threads produce significant improvements in stroke induction by MCA occlusion, particularly in aged animals and those with co-morbidities.

[1]  T. Jones,et al.  Long-Lasting Functional Disabilities in Middle-Aged Rats with Small Cerebral Infarcts , 2003, The Journal of Neuroscience.

[2]  H. Reulen,et al.  A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. , 1998, Stroke.

[3]  Stroke Therapy Academic Industry Roundtable Recommendations for standards regarding preclinical neuroprotective and restorative drug development. , 1999, Stroke.

[4]  Aspey,et al.  Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke , 1998, Neuropathology and applied neurobiology.

[5]  Takeshi Hayashi,et al.  Different expression of glycogen synthase kinase-3β between young and old rat brains after transient middle cerebral artery occlusion , 2001, Neurological research.

[6]  R. Traystman,et al.  Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. , 2000, Stroke.

[7]  G. Donnan,et al.  Imaging the Ischemic Penumbra with 18F-Fluoromisonidazole in a Rat Model of Ischemic Stroke , 2004, Stroke.

[8]  A reproducible model of middle cerebral infarcts, compatible with long-term survival, in aged rats. , 1995, Stroke.

[9]  K. Kogure,et al.  Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. , 1989, Stroke.

[10]  R. Laing,et al.  Middle Cerebral Artery Occlusion Without Craniectomy in Rats: Which Method Works Best? , 1993, Stroke.

[11]  P. Weinstein,et al.  Reversible middle cerebral artery occlusion without craniectomy in rats. , 1989, Stroke.

[12]  B. Aspey,et al.  Temporary middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke and reperfusion , 2000, Neuropathology and applied neurobiology.

[13]  M. Fisher,et al.  Reproducibility and reliability of middle cerebral artery occlusion using a silicone-coated suture (Koizumi) in rats , 1997, Journal of the Neurological Sciences.

[14]  M D Ginsberg,et al.  Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. , 1996, Stroke.

[15]  K Minematsu,et al.  Nylon monofilament for intraluminal middle cerebral artery occlusion in rats. , 1995, Stroke.

[16]  Yoji Yoshida,et al.  Experimental studies of ischemic brain edema , 1986 .

[17]  G. Sutherland,et al.  Effect of age in rodent models of focal and forebrain ischemia. , 1996, Stroke.