Review Article

Rodent Models of Developmental Ischemic Stroke for Translational Research: Strengths and Weaknesses

Table 1

Summary of main rodent models of the developmental stroke used in translational research.

AnimalAge of lesion inductionMethod of inductionAge of assessmentVariables assessed

Rat [40, 49, 63, 73, 79, 80, 180183, 185, 186]; mouse [49, 61, 63, 64]P7 [40, 49, 63, 73, 80, 180183, 185, 186]; P9 [61, 64]; P10 [79]; P3 [175]Hypoxia-ischemia based on the Levine-Rice methodUp to P11 [189]; P9 [40, 73, 181, 183]; P8 [190]; up to P67 [191]; P12 [63, 175, 182]; P21 [175, 185]; within 3 hr after lesion [186]; P11 and P40 [79]; from P21 to P60 [80]; up to P10 [40]; 6 hr post-HI and at P16 [61]; P31 [64]Analysis of damage by MRI [73, 189]; analysis of brain edema by histology [192]; behavioral assessment of sensorimotor function [73]; analysis of intracellular calcium accumulation [190]; phosphocreatine, neuronal MAP-2, SNAP-25, and glial GFAP [193]; analysis of lesion volume and of white matter injury by histology [49, 61, 73, 187, 191, 192, 194]; analysis of systemic physiological variables (mean arterial blood pressure, heart rate, PO2, PCO2, pH, lactate, and glucose) and of high-energy phosphate and glycolytic intermediates [195]; effects of adiponectin treatment efficacy on the brain infarct area, apoptosis, brain atrophy, and neurological function [79]; investigation of efficacy of combining constraint-induced movement therapy (CIMT) and electroacupuncture on motor asymmetry and on lesion size and astrogliosis [80]; analysis of the role of AMPK signaling in the developing rat brain with HI [40]; analysis of inflammatory activation by immunohistochemistry [187]; assessment of oxidative stress after injury [49]; assessment of JAK/STAT signaling in brain inflammation [61, 63] and neuroprotection [63] by biochemical, molecular, and histological approaches [61, 63]; role of GFAP deletion on astrogliosis after HI and on infarct volume by immunohistochemistry [64]

RatP7Embolus MCAOUp to P8Analysis of lesion volume by histology [88]

RatP7MCA electrocoagulation associated with 1-hour left CCAOUp to P90Analysis of inflammatory responses by histology [196]

Rat [59, 65, 85, 86, 91, 188, 189]; mouse [60]P14-P18 [85]; P7 [30, 59, 60, 67, 86, 188, 189]; P10 [65, 91]Transient MCAOP8 [85]; up to P90 [188]; P8 [67] up to P10 [60, 189]; P8 [30]; P10 [91]; P8 and P10 [59]; up to P38 [65]Analysis of lesion volume by histology [59, 65, 85, 86, 91, 197, 198]; analysis of lesion evolution by MRI [59, 65, 67] and neuroprotection assessment [30, 91]; microglia activation by histology [59]; BBB integrity postinjury by histological, biochemical, and molecular techniques [67]; assessment of the role of microglia on hemorrhages by histological, biochemical, and molecular techniques [60]; assessment of brain edema through brain aquaporin-4 expression profiling [65]

Mouse [30, 89, 90]P12 [92]; P7 [30]; P20-25 [89]MCAOUp to P68 [90]; P8 [30]; 22 hr after lesion [89]Analysis of lesion volume by histology and behavioral assessment of functional deficits [92]; anatomical analysis of caspase-3 activation in the ischemic core and penumbra [30]; effects of ischemia and estrogen treatment on the proapoptotic gene Bax [89]

Mouse [76, 77]From P3 to P10 [76]; from P3 to P10 [77]Chronic hypoxiaP10 and P48 [76]; P18 and P48 [77]Analysis of injury by histology and unbiased stereological analysis of neurogenesis by BrdU assay [76, 77]

RatP7PhotothrombosisP12 and P25Study of PTZ-seizure susceptibility by EEG recordings [100]

Rat [103105]P14 [103]; P21 [103, 104]; P12 and P25 [105]ET1 injection: intracortical [103]; intrastriatal [104]; intrahippocampal [105]From P60 [103]; not specified [104]; up to 22 hr postinjury [105]Assessment of lesion timing on damage volume, long-term motor outcome, and axonal sprouting of contralesional CST at the red nucleus and spinal cord level using anterograde tracing [122]; MRI analysis of damage extension, CBF volume and metabolic changes, and BBB integrity [123]; assessment of ischemia-induced seizures by video/EEG recordings [124]