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Review
. 2012 Jul 6;10:139.
doi: 10.1186/1479-5876-10-139.

Standards and Pitfalls of Focal Ischemia Models in Spontaneously Hypertensive Rats: With a Systematic Review of Recent Articles

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Free PMC article
Review

Standards and Pitfalls of Focal Ischemia Models in Spontaneously Hypertensive Rats: With a Systematic Review of Recent Articles

Hiroshi Yao et al. J Transl Med. .
Free PMC article

Abstract

We reviewed the early development of various focal ischemia models in spontaneously hypertensive rats (SHR), and summarized recent reports on this topic. Among 6 focal ischemia models established in divergent substrains of SHR, distal middle cerebral artery occlusion is the most frequently used and relevant method of focal ischemia in the light of penumbra concept. We performed an online PubMed search (2001-2010), and identified 118 original articles with focal ischemia in SHR. Physiological parameters such as age, body weight, and even blood pressure were often neglected in the literature: the information regarding the physiological parameters of SHR is critical, and should be provided within the methodology section of all articles related to stroke models in SHR. Although the quality of recent studies on neuroprotective strategy is improving, the mechanisms underlying the protection should be more clearly recognized so as to facilitate the translation from animal studies to human stroke. To overcome the genetic heterogeneity in substrains of SHR, new approaches, such as a huge repository of genetic markers in rat strains and the congenic strategy, are currently in progress.

Figures

Figure 1
Figure 1
Focal ischemia models in divergent substrains of spontaneously hypertensive rats (SHR). SHR were sent to National Institute of Health (NIH) at the F13 generation in 1966 (SHR/N), and then from NIH to Charles River, Taconic Farms, and Harlan. In France, Iffa-Credo received their original breeding stocks of SHR from NIH in 1976, and Janvier started breedings in 1978 with SHR derived from the Delalande Research Center, which in turn received their original breeding stocks from Kyoto University in 1974. Two colonies of SHRSP (SHRSP/A3N [NIH] and SHRSP/Bbb [Heidelberg]) were separated at F35, 36 in 1975. CNRS, Centre National de la Recherche Scientifique; SHRSP or SP, stroke prone SHR: NIH, National Institute of Health; MCAO, middle cerebral artery occlusion; d, distal; p, proximal; CCAO, common carotid artery occlusion; YAG, yttrium-aluminium-garnet (laser).
Figure 2
Figure 2
Schematic representation of the ischemic penumbra. Glucose utilization (anaerobic glycolysis) transiently increases at a CBF value below about 40% of normal, which corresponds to the beginning of acidosis with lactate accumulation. At a CBF value below about 20% of normal, a breakdown of energy state begins with reduced adenosine triphosphate (ATP), resulting in the condition of ischemic core. The penumbra is defined as an area in which metabolism is impaired due to reduced CBF, but the cellular polarization is still maintained without diffusion- weighted imaging lesions on magnetic resonance imaging. Therefore, an acidosis/diffusion- weighted imaging mismatch represents penumbra.
Figure 3
Figure 3
Box and whisker plot of resting mean arterial blood pressure in experiments with low and high concentrations of anesthesia. The box shows median value and 25th and 75th percentiles. *P=0.000 for difference in mean arterial blood pressure between the groups (Mann–Whitney u-test).

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