Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia studies in the rat: A comparative study

Abstract

Abstractα-chloralose is widely used as an anesthetic in studies of the cerebrovasculature because it provides robust metabolic and hemodynamic responses to functional stimulation. However, there have been no controlled studies of focal ischemia in the rat under α-chloralose anesthesia. Artificially ventilated rats were prepared using 1.2−1.5 % isoflurane anesthesia for filament occlusion of the right middle cerebral artery (MCA), and anesthesia was either switched to α-chloralose (60 mg/kg bolus, 30 mg/ kg/hr; n=10) or was maintained on 1% isoflurane (n=10). Following temporary MCA occlusion EEG was monitored from a screw electrode and changes in cerebral blood flow (rCBF) measured with a laser Doppler probe placed over the ischemic cortex. This study shows that α-chloralose is a safe anesthetic for ischemia studies and provides excellent survival. Compared with isoflurane, the cortical and total infarct volumes are larger in the α-chloralose anesthetized animals, while the functional outcome at 72 hours is similar. The total duration of peri-infarct flow transients (PIFTs) is also significantly longer in α-chloralose anesthetized animals. The average amplitude of the flow transients showed a good correlation with the extent of edema in all animals as did the total duration of non-convulsive seizures (NCS) in the α-chloralose anesthetized animals.

The predictive value of peri-infarct flow transients in focal brain ischemia

“…As discussed above (see Laser Doppler Flowmetry), the criteria for the detection of PIFTs using one LDF probe have been established previously (Luckl et al, 2008(Luckl et al, , 2009. In the present study we determined that PIFTs are in fact associated with negative DC shifts typical of spreading depolarization.…”

“…Residual flow during ischemia (0-90th min) and the reperfusion (0-10th min) were calculated as percentage of baseline prior to MCAO. Criteria for identifying PIFTs have been established previously based on LD recordings with two probes and the comparison of simultaneous LD and LS monitoring during filament MCAO in the rat (Luckl et al, 2008(Luckl et al, , 2009): (a) flow transient with amplitude greater than 5% of pre-ischemic baseline; (b) duration of CBF changes longer than 60 s; and (c) stable blood pressure during the event. Since our original description of the criteria for identifying PIFTs we found in a few animals that the amplitudes of PIFTs can also be 3-4% (lower than 5%) in animals with more severe ischemia (intraischemic CBF less than 20%).…”

On the use of α-chloralose for repeated BOLD fMRI measurements in rats

“…Therefore, providing a comfortable breathing position even in an oxygen enriched environment increases the survival rate. In fact previous research using tracheotomy during experimentation and oxygen enriched environment during recovery have shown a complete survival rate too (Luckl et al, 2008).…”

“…(Balis and Monroe, 1964) and reported a lethal dose of 120 mg/kg. Furthermore, new studies measuring stroke effects in rats by laser Doppler flow show that AC can be recoverable (Luckl et al, 2008). To our knowledge, the nonrecoverable concept has not been challenged lately for its use in fMRI.…”

Cornel iridoid glycoside reduces infarct size measured by magnetic resonance imaging and improves neurological function after focal cerebral ischemia in rats

“…(14) In murine ischemia/reperfusion models, many studies have evaluated the change of infarct size. (21)(22)(23) An increase in T2 signal can be seen extremely early in the infarct area, which is indicative of edema and breakdown of the bloodbrain barrier. (13,(24)(25)(26) In the present study, we found that 2 days after MCAO, when cerebral edema reaches its maximum, (27,28) the T2-weighted signal was increased in the damaged area.…”