Table 2.

Summary of Animal Models for the Study of Preeclampsia and Associated Offspring Phenotype^a

Model	General findings	Offspring neurobiology	Refs
AVP infusion in mice	Dams: gestation-specific hypertension, renal dysfunction, proteinuria; ↑ interferon (IFN)g, IL-17; ↓ IL-4, IL-10 Placentas: ↓ PlGF, altered morphology, blood flow, oxidative stress, and immune dysregulation; ↑ IL-17 Fetuses: growth restriction; ↑ IL-17; ↓ IL-4, IL-10	n/a	[40,89]
IL-17 manipulation in rats	Dams: hypertension, oxidative stress; ↑ IL-6, TNFα, IL-17 Placentas: oxidative stress	n/a	[96,97]
L-NAME treatment in rats	Dams: hypertension, renal dysfunction, proteinuria, oxidative stress; angiogenic dysfunction; stillbirths Placentas: inflammation, structural changes Fetuses: growth restriction	↓ Neonatal brain weight, neurogenesis; ↑ adult gliogenesis; ↓ learning, memory, hippocampal neurogenesis and glucocorticoid receptor expression; neonatal and adult brain ↑ microglial protein, and ↓ glial glutamate transporter protein	[62b,99,100b,102b,117]
PlGF deficiency in mice	Impaired adult angiogenesis and revascularization, abnormal vascular permeability/growth, and inflammation	Impaired memory, locomotor, anxiety- and depressive-like behavior; ↓ regional brain volumes; cerebral blood vessel changes	[69b,70b,105b,106]
RUPP in rats	Dams: hypertension, ↑ sFlt-1, renal dysfunction, proteinuria, oxidative stress; ↑ cortical water; neuroinflammation; altered astrocyte, microglia numbers; ↓ litter size Placentas: hypoxia, inflammation, oxidative stress Fetuses: ↑ hematocrit	↓ fetal brain microglia, ↑ cerebral micro-bleeds, neuroinflammation; cortical thickness unchanged	[52b,76,77,91,114–116,118]
Angiogenic dysregulation and systemic inflammation in mice	Dams: hypertension and albuminuria Fetuses: growth restriction; altered metabolism	n/a	[61]
Impaired umbilical circulation in sheep	Fetuses: ↑ hypoxemia	In fetal cortex: gliosis, myelination, neuronal process defects; white matter lesions; abnormal cerebrovasculature; ↓ Purkinje neurons	[78]

^aSee Table S2 in the supplemental information online for details of each study.

^bReference contains neurobiological offspring outcomes.