Comparison of Different Preclinical Models of Intracerebral Hemorrhage

Abstract

Intracerebral hemorrhage (ICH) is the most devastating type of stroke. It is characterized by spontaneous bleeding in brain parenchyma and is associated with a high rate of morbidity and mortality. Presently, there is neither an effective therapy to increase survival after intracerebral hemorrhage nor a treatment to improve the quality of life for survivors. A reproducible animal model of spontaneous ICH mimicking the development of acute and delayed brain injury after ICH is an invaluable tool for improving our understanding of the underlying mechanisms of ICH-induced brain injury and evaluating potential therapeutic interventions. A number of models have been developed. While different species have been studied, rodents have become the most popular and widely utilized animals used in ICH research. The most often used methods for experimental induction of ICH are injection of bacterial collagenase and direct injection of blood into the brain parenchyma. The “balloon” method has also been used to mimic ICH for study. In this summary, we intend to provide a comparative overview of the technical methods, aspects, and pathologic findings of these types of ICH models. We will also focus on the similarities and differences among these rodent models, achievements in technical aspects of the ICH model, and discuss important aspects in selecting relevant models for study.

Acute and delayed protective effects of pharmacologically induced hypothermia in an intracerebral hemorrhage stroke model of mice

“…The blood injection-induced ICH model may not fully reflect the pathology of clinical hemorrhagic stroke. In this case, the use of the collagenase-induced ICH model might be an alternative methodology to investigate the mechanism of the PIH effect (Manaenko et al, 2011). Additionally, the duration of hypothermia was 6 hrs in our experiments.…”

Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury

“…62 Furthermore, because of the diffuse activity of collagenase, rebleeding is often achieved. 81 Neurological deficits seen in this model are typically more severe than in whole-blood injection, 45 and animals do not frequently exhibit spontaneous recovery.…”

“…Furthermore, this model does not achieve the rebleeding phenomenon that is typical of clinical ICH. 43 Finally, injection of whole blood produces a less severe neurological deficit than seen in the clinical setting 45 and can even allow for spontaneous recovery. 21,33,70 In the collagenase model, bacterial collagenase is injected into the caudate nucleus to erode the basal lamina of blood vessels and induce in situ hemorrhage.…”

“…45 Both ICH models are performed in rodents, which are relatively inexpensive to house, genetically modifiable, and have well-established parameters for functional assessment. 40 However, mice and rats are disadvantaged by a relative lack of white matter when compared with humans.…”

Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage

“…Although promising, the potential efficacy of progesterone after ICH remains unclear and must be fully explored before its prospective therapeutic value can be tested in clinical trials. To this end and to closely mimic the human disease, we employed a rat model of collagenous-induced intrastriatal ICH for its consistent and reproducible hematoma with expansion over the initial 24 h [43]. Sex differences in the response to progesterone treatment after ICH were investigated.…”