Animal models of spontaneous intracerebral hemorrhage.
OBJECTIVE
Intracerebral hemorrhage (ICH) is a type of stroke that results in significant mortality and morbidity. Currently there is no definitive treatment for this disease. The paucity of animal models that reflect the heterogeneity of this spontaneous human disease could be the reason.


METHODS
In this review, we searched the literature for animal models of spontaneous ICH and found eight relevant papers.


RESULTS
Two were related to hypertension and six were related to cerebral amyloid angiopathy (CAA). One model used double transgenic mice overexpressing human renin and angiotensinogen which caused the mice to be hypertensive. Induction of ICH, however required addition of a high salt diet and nitric oxide synthase inhibition. Another mouse model of hypertension employed subcutaneous angiotensin II infusion and nitric oxide synthase inhibition plus acute injections of angiotensin to further elevate blood pressure. Five CAA models were in transgenic mice overexpressing amyloid precursor protein. One relied on the natural development of CAA in squirrel monkeys.


CONCLUSIONS
While all of the spontaneous ICH models have some advantages, the disadvantages include the sporadic time of onset of ICH and variability in size and location of ICH. Since there are no known efficacious treatments for ICH, it is not known if findings in the animal models will find treatments that are effective in humans.
a Division of Neurosurgery , St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital , Toronto , Ontario , Canada.|b Department of Surgery , University of Toronto , Toronto , Ontario , Canada.
Bader Murshed
BM
Alharbi
a Division of Neurosurgery , St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital , Toronto , Ontario , Canada.|b Department of Surgery , University of Toronto , Toronto , Ontario , Canada.
Michael K
MK
Tso
a Division of Neurosurgery , St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute of St. Michael's Hospital , Toronto , Ontario , Canada.|b Department of Surgery , University of Toronto , Toronto , Ontario , Canada.
R Loch
RL
Macdonald
D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000209:etiology; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D008822:Mice, Transgenic; D012307:Risk Factors
Animal model; Cerebral amyloid angiopathy; Hypertension; Intracerebral hemorrhage; Spontaneous