Effect of anesthesia and cerebral blood flow on neuronal injury in a rat middle cerebral artery occlusion (MCAO) model

Abstract

Middle cerebral artery occlusion (MCAO) models have become well established as the most suitable way to simulate stroke in experimental studies. The high variability in the size of the resulting infarct due to filament composition, rodent strain and vessel anatomy makes the setup of such models very complex. Beside controllable variables of homeostasis, the choice of anesthetics and the grade of ischemia and reperfusion played a major role for extent of neurological injury. Transient MCAO was induced during either isoflurane or ketamine/xylazine (ket/xyl) anesthesia with simultaneously measurement of cerebral blood flow (CBF) in 60 male Wistar rats (380-420 g). Neurological injury was quantified after 24 h. Isoflurane compared with ket/xyl improved mortality 24 h after MCAO (10 vs. 50 %, p = 0.037) and predominantly led to striatal infarcts (78 vs. 18 %, p = 0.009) without involvement of the neocortex and medial caudoputamen. Independent of anesthesia type, cortical infarcts could be predicted with a sensitivity of 67 % and a specificity of 100 % if CBF did not exceed 35 % of the baseline value during ischemia. In all other cases, cortical infarcts developed if the reperfusion values remained below 50 %. Hyperemia during reperfusion significantly increased infarct and edema volumes. The cause of frequent striatal infarcts after isoflurane anesthesia might be attributed to an improved CBF during ischemia (46 ± 15 % vs. 35 ± 19 %, p = 0.04). S-100β release, edema volume and upregulation of IL-6 and IL-1β expression were impeded by isoflurane. Thus, anesthetic management as well as the grade of ischemia and reperfusion after transient MCAO demonstrated important effects on neurological injury.

Hemodynamic effects of intraoperative anesthetics administration in photothrombotic stroke model: a study using laser speckle imaging

“…For instance, a longitudinal MRI study carried out between 6 h and 21 days after ischemia showed that isoflurane altered regional CBF and constrained the deleterious hemodynamic variation in ischemia reperfusion injury [12]. LDF is an in vivo real-time imaging technique, which has been commonly utilized to monitor transient focal CBF throughout surgery or during the induction of ischemia [26, 27]. For example, Bleilevens et al [27] observed the focal CBF in the ischemic area of isoflurane anesthetized rats by LDF at various time points before and after the onset of ischemia, finding significantly higher values at 50 min after ischemia in comparison with ketamine/xylazine anesthetized rats.…”

“…LDF is an in vivo real-time imaging technique, which has been commonly utilized to monitor transient focal CBF throughout surgery or during the induction of ischemia [26, 27]. For example, Bleilevens et al [27] observed the focal CBF in the ischemic area of isoflurane anesthetized rats by LDF at various time points before and after the onset of ischemia, finding significantly higher values at 50 min after ischemia in comparison with ketamine/xylazine anesthetized rats. Compared with LDF, LSI provides full-field CBF information with high spatial and temporal resolution [28].…”

Effects of Quercetin and Mannitol on Erythropoietin Levels in Rats Following Acute Severe Traumatic Brain Injury

“…Forty male Wistar rats (weight, 318.3±5 g) were divided randomly into four groups (n=10/group): group I, sham; group II, TBI; group III, TBI+quercetin (50 mg/kg intravenous); and group IV, TBI+mannitol (1 mg/kg intravenous). The rats were anesthetized intraperitoneally with 100 mg/kg s-ketamine (Ketanest S; Pfizer, New York, NY, USA) and 10 mg/kg xylazine (Xylazin 2%; Medistar, Ascheberg, Germany)7).…”

Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential involvement of deep cerebral arteries?

“…Anesthetic drugs have a strong influence on murine hypotension, which should be taken into account in experiments (Schwarzkopf et al, 2013). When isoflurane is used, infarct volumes in MCAO animals are smaller than those in animals anesthetized with ketamine/xylazine (Zhao et al, 2008;Bleilevens et al, 2013). This could be explained by the fact that, volatile anesthetics inhibit NMDA and AMPA receptors while ketamine blocks only the NMDA receptor and that isoflurane leads to cerebral vasodilatation (Kehl et al, 2002).…”