A modified suture technique produces consistent cerebral infarction in rats

Abstract

Intraluminal occlusion of the middle cerebral artery (MCA) is used extensively in cerebral ischemia research. We tested a modified nylon suture in a rat model of middle cerebral artery occlusion (MCAO) under two anesthesia regimens. Sprague-Dawley rats were divided into six groups (Group 1, Poly-L-lysine-coated suture under ketamine/xylazine anesthesia; Group 2, modified suture under ketamine/xylazine anesthesia; Group 3, Poly-L-lysine-coated suture under ketamine/xylazine anesthesia with mechanical ventilation; Group 4, modified suture under ketamine/xylazine anesthesia with mechanical ventilation; Group 5, Poly-L-lysine-coated suture under isoflurane anesthesia; Group 6, modified suture under isoflurane anesthesia) and subjected to 2 hours MCAO. Regional cerebral blood flow (rCBF) was monitored by Laser-Doppler flowmetry. Neurological evaluation and ischemic lesion (TTC stain) were assessed at 24 hr of reperfusion. The total ischemic lesion (sum of areas with lacking and intermediate TTC staining) was similar among all six groups. Compared with a Poly-L-lysine-coated suture technique, the modified suture technique produced a lower rCBF, larger infarct size, smaller variance of infarct size, and greater neurological deficit. In addition, isoflurane significantly reduced infarct size. We conclude that use of this modified suture technique with ketamine/xylazine anesthesia and mechanical ventilation produces a more consistent change in cerebral ischemic damage following MCAO in rats.

Mitochondrial function and cerebral blood flow variable responses to middle cerebral artery occlusion

“…Early unexpected reperfusion may be an indication to an incomplete occlusion (Hungerhuber et al, 2006). which may be attributed to spontaneous withdrawal of the occluding filament, or abnormality in blood vessel anatomy (Gerriets et al, 2004;Zhao et al, 2008). Our results showed spontaneous reperfusion was distributed almost equally in all of the ischemic durations and therefore is unlikely influenced by the length of the ischemia.…”

“…However, as previously reported by many studies, the induction of MCAO in rats may not always lead to the anticipated outcomes, as expressed by the variability in neurological scores, size of infarct, cases of sub-arachnoid haemorrhage and occurrence of death (Laing et al, 1993;Schmid-Elsaesser et al, 1998;Gerriets et al, 2004;Lourbopoulos et al, 2008;Zhao et al, 2008). Up to date, no report that characterized the experiments that failed and examined their patterns was published.…”

“…Collateral pathways usually lead to better perfusion in the penumbra compared to the core (Lipton, 1999). Studies show that MCAO tend to be variable in their lesion size and magnitude due to variance in collateral blood supply (Lee et al, 2007), or abnormal anatomy of cerebral blood vessels (Gerriets et al, 2004;Zhao et al, 2008). Normal or elevated blood supply, accompanied by regular mitochondrial activity, might be an outcome of abnormal collateral pathways and may explain the variability in some of the mentioned studies.…”

An experimental model of focal ischemia using an internal carotid artery approach

“…This fact might be explained by the more complete occlusion of the MCA with the siliconecoated thread, and the closure of additional collateral arteries supplying the hemisphere such as the hypothalamic artery, anterior choridal artery, and posterior communicating artery (Fox et al, 1993). The silicone-coated thread may be able to better occlude the MCA in rats who have anatomical variations in both the MCA and the circle of Willis (approximately 17% of all rats) (Fox et al, 1993;Niiro et al, 1996;Zhao et al, 2008), such as a more distal or proximal origin of the MCA, or accessory arteries feeding the MCA. When compared to the silicone-coated thread, the monofilament offers a rather fixed point of occlusion with no ability to compensate for anatomic variations.…”

Secondary Damage in the Spinal Cord after Motor Cortex Injury in Rats

“…We chose devascularization because it is a well-established method for generating ischemic lesions that reliably damage all layers of the cortex in a defined area (Whishaw, 2000). In addition, the consistency in lesion volume and location is far superior to other forms of ischemic injury, such as middle cerebral artery occulsion or endothelin injection (Windle et al, 2006;Zhao et al, 2008).…”