A Comparative Study of Koizumi and Longa Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Rats: Early Corticosterone and Inflammatory Response in the Hippocampus and Frontal Cortex

Abstract

Two classical surgical approaches for intraluminal filament middle cerebral artery occlusion (MCAO), the Longa et al. (LM) and Koizumi et al. methods (KM), are used as alternatives in preclinical studies to induce stroke in rodents. Comparisons of these MCAO models in mice showed critical differences between them along with similarities (Smith et al. 2015; Morris et al. 2016). In this study, a direct comparison of MCAO-KM and MCAO-LM in rats was performed. Three days after MCAO, infarct volume, mortality rate, neurological deficit, and weight loss were similar in these models. MCAO-LM rats showed an increase in ACTH levels, while MCAO-KM rats demonstrated elevated corticosterone and interleukin-1β in blood serum. Corticosterone accumulation was detected in the frontal cortex (FC) and the hippocampus of the MCAO-KM group. IL1β beta increased in the ipsilateral hippocampus in the MCAO-KM group and decreased in the contralateral FC of MCAO-LM rats. Differences revealed between MCAO-KM and MCAO-LM suggest that corticosterone and interleukin-1β release as well as hippocampal accumulation is more expressed in MCAO-KM rats, predisposing them to corticosterone-dependent distant neuroinflammatory hippocampal damage. The differences between two models, particularly, malfunction of the hypothalamic–pituitary–adrenal axis, should be considered in the interpretation, comparison, and translation of pre-clinical experimental results.

A Comparative Study of Two Models of Intraluminal Filament Middle Cerebral Artery Occlusion in Rats: Long-Lasting Accumulation of Corticosterone and Interleukins in the Hippocampus and Frontal Cortex in Koizumi Model

“…It should be noted that the hippocampus and prefrontal cortex are central structures of the cortico–limbic network associated with both cognitive processes (e.g., learning and memory) and the control of emotions [ 46 ], whereas their dysconnectivity may underlie different brain diseases [ 47 ]. This may explain why both in our previous [ 15 ] and present study, we found similar trends to the increased corticosterone accumulation both in the hippocampus and FC of the MCAO-KM rats. Importantly, the accumulation of corticosterone and Il1β in the hippocampus and FC was not only in the injured but also in the contralateral hemisphere, which substantiates the hypothesis of potential distant damage.…”

“…For rats showing a neurological deficit according to the 5-point scale, the survival rate within 48 h was 52% (12 of 23) for the MCAO-KM rats and 52% (11 of 21) for the MCAO-LM rats; the survival within 3 months was 35% (8 of 23) and 43% (9 of 21), respectively. The short-term survival did not differ significantly from the data reported previously for the MCAO-KM (57% within 72 h) and the MCAO-LM (63%) [ 15 ]. Similar to the reports of Smith et al [ 13 ] and Morris et al [ 14 ], in mice, the mortality did not differ in the MCAO-LM and MCAO-KM and was very high during the first 24 h after MCAO (e.g., the after 60 min occlusion survival rate was 38.5% within 24 h in the MCAO-KM mice).…”

“…These MCAO models in mice were directly compared and, though similar in many respects, showed significant differences [ 13 , 14 ]. Recently, we have performed a direct comparison of MCAO-KM and MCAO-LM in rats during the early post-ischemic period [ 15 ]. We showed a lack of differences in the infarct volume, mortality rate, neurological deficits, and weight loss in these models 3 days after MCAO.…”

“…Critical surgery-specific differences were found in these two MCAO models in mice, including significantly greater reperfusion in the MCAO-LM [ 14 ] and a greater and more robust inflammatory response in the MCAO-LM [ 13 ]. As the MCAO-KM or MCAO-LM in rats, similar to the respective MCAO models in mice, are presently used randomly, and, most importantly, the data are compared without taking into account the specific features of each model, we have recently studied the early post-stroke period in the MCAO-KM and MCAO-LM in rats and found that, though the infarct volumes and neurological deficits were similar in both models, the MCAO-KM rats demonstrated a greater secretion and accumulation in the hippocampus and FC of corticosterone and IL1β [ 15 ]. In the present study, we confirmed our previous data showing a lack of difference between the models in terms of neurological deficits and body mass changes during the first two weeks after the surgery ( Figure 2 ).…”

“…Comparisons of these MCAO models in mice demonstrated significant dissimilarities between them along with an obvious resemblance [ 13 , 14 ]. Recently, we have performed a direct comparison of the Koizumi model (MCAO-KM) and Longa model (MCAO-LM) in rats [ 15 ]. Though the infarct volume, mortality rate, neurological deficits, and weight loss were similar in the MCAO-KM and MCAO-LM rats, during the acute period, the MCAO-KM animals showed elevated corticosterone (CS) and interleukin-1β (IL1β) in blood serum.…”