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Comparative Study
. 2021 Dec 17;22(24):13544.
doi: 10.3390/ijms222413544.

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

Mikhail V Onufriev  1   2 , Yulia V Moiseeva  1 , Marina Y Zhanina  1   2 , Natalia A Lazareva  1 , Natalia V Gulyaeva  1   2
Affiliations
Comparative Study

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

Mikhail V Onufriev et al. Int J Mol Sci. .

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.

Keywords: adrenocorticotropic hormone; corticosterone; distant damage; frontal cortex; hippocampus; interleukins; middle cerebral artery occlusion; neuroinflammation; stroke.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Neurological deficits (a,b), weight loss (c), and infarct volume (d) in MCAO-KM and MCAO-LM. (a) 5-score test after surgery (day 0), 1, and 3 days after surgery. (b) Tongue protrusion test 1 and 3 days after surgery; % of initial values. (c) Body mass 3 days after surgery; % of initial mass. (d) Infarct volume 3 days after surgery; % of the contralateral hemisphere; examples of TTC-stained frontal slices −4.5 ÷ −6.5 mm from bregma. ** p < 0.01 compared to the respective sham-operated groups.
Figure 2
Figure 2
Blood levels of corticosterone (a), ACTH (b), and IL1β (c) in the MCAO-KM and MCAO-LM groups 3 days after surgery. (a) Corticosterone, nmol/mL. (b) ACTH, ng/mL. (c) IL1β, pg/mL. ** p < 0.01, * p < 0.05, and + p < 0.1 compared to the respective sham-operated groups or control rats.
Figure 3
Figure 3
Corticosterone levels in the hippocampus (a,b) and FC (c,d) in MCAO-KM and MCAO-LM groups 3 days after surgery. (a) Ipsilateral hippocampus. (b) Contralateral hippocampus. (c) Ipsilateral FC. (d) Contralateral FC. (a–d) Corticosterone, pmol/g tissue.** p < 0.01, * p < 0.05, and + p < 0.1 compared to the respective sham-operated groups or control rats.
Figure 4
Figure 4
IL1β levels in the hippocampus (a,b) and FC (c,d) in MCAO-KM and MCAO-LM groups 3 days after surgery. (a) Ipsilateral hippocampus. (b) Contralateral hippocampus. (c) Ipsilateral FC. (d) Contralateral FC. (a–d) IL1β, pg/g tissue. * p < 0.05 and + p < 0.1 compared to the respective sham-operated groups or control rats.
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