Rat middle cerebral artery occlusion is not a suitable model for the study of stroke-induced spontaneous infections

PLoS One. 2014 Jun 12;9(6):e99169. doi: 10.1371/journal.pone.0099169. eCollection 2014.

Abstract

Background: Infections related to stroke-induced immunodepression are an important complication causing a high rate of death in patients. Several experimental studies in mouse stroke models have described this process but it has never been tested in other species such as rats.

Methods: Our study focused on the appearance of secondary systemic and pulmonary infections in ischemic rats, comparing with sham and naive animals. For that purpose, male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) or to transient MCAO (tMCAO) inserting a nylon filament. Forty-eight hours after ischemia, blood and lung samples were evaluated.

Results: In eMCAO set, ischemic rats showed a significant decrease in blood-peripheral lymphocytes (naive = 58.8±18.1%, ischemic = 22.9±16.4%) together with an increase in polymorphonuclears (PMNs) (naive = 29.2±14.7%, ischemic = 71.7±19.5%), while no change in monocytes was observed. The increase in PMNs counts was positively correlated with worse neurological outcome 48 hours after eMCAO (r = 0.55, p = 0.043). However, sham animals showed similar changes in peripheral leukocytes as those seen in ischemic rats (lymphocytes: 40.1±19.7%; PMNs: 51.7±19.2%). Analysis of bacteriological lung growth showed clear differences between naive (0±0 CFU/mL; log10) and both sham (3.9±2.5 CFU/mL; log10) and ischemic (4.3±2.9 CFU/mL; log10) groups. Additionally, naive animals presented non-pathological lung histology, while both sham and ischemic showed congestion, edema or hemorrhage. Concordant results were found in the second set of animals submitted to a tMCAO.

Conclusions: Inflammatory and infection changes in Wistar rats subjected to MCAO models may be attributed not only to the brain ischemic injury but to the surgical aggression and/or anaesthetic stress. Consequently, we suggest that stroke-induced immunodepression in ischemic experimental models should be interpreted with caution in further experimental and translational studies, at least in rat stroke models that entail cervicotomy and cranial trepanation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coinfection / etiology*
  • Coinfection / immunology
  • Disease Models, Animal
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / immunology
  • Lymphocyte Subsets*
  • Male
  • Postoperative Complications / immunology
  • Rats
  • Rats, Wistar
  • Respiratory Tract Infections / etiology*
  • Respiratory Tract Infections / immunology
  • Sepsis / etiology*
  • Sepsis / immunology

Grants and funding

MC is supported by a FIS grant (FI 10/00508) from the Spanish Ministry of Health, and MHG and AR are senior researchers of the Miguel Servet Programme (CP12/03259 and CP09/00265), all those from the Instituto de Salud Carlos III from the Spanish Ministry of Economy. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements n ° 201024 and n ° 202213 (European Stroke Network), Eurosalud Programme (EUS2008-03610) and the Spanish stroke research network INVICTUS (RD12/0014/0005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.