Germinal matrix hemorrhage refers to bleeding that arises from the subependymal (or periventricular) germinal region of the immature brain. Clinical studies have shown that infants who experience germinal matrix hemorrhage can develop hydrocephalus or suffer from long-term neurologic dysfunction, including cerebral palsy, seizures, and learning disabilities. Understanding the causative factors and the pathogenesis of subsequent brain damage is important if germinal matrix hemorrhage is to be prevented or treated. Appropriate animal models are necessary to achieve this understanding. A number of animal species, including mice, rats, rabbits, sheep, pigs, dogs, cats, and primates, have been used to model germinal matrix hemorrhage. This literature review critically evaluates the animal models of germinal matrix hemorrhage. Each model has its own advantages and disadvantages; no single model is suitable for the study of all aspects of brain damage.

Periventricular/intraventricular hemorrhage (PVH/IVH) into brain can occur in premature infants and is associated with poor developmental outcome. The purpose of this study was to develop and characterize a model of PVH/IVH in newborn mouse. We hypothesized that periventricular germinal matrix would exhibit reduced cell proliferation. PVH/IVH was induced in 1-day-old mice by injection of autologous blood into the periventricular tissue. Magnetic resonance images (MRI) were obtained from 15 minutes to 14 days later. Mice were killed 4 hours to 28 days later. Cell proliferation, dying cells, astrocyte and microglial reactions, neutrophils, and lymphocytes were quantified. Histological studies showed that MRI accurately localizes the hematoma but overestimates its size. The hematoma, located in the striatum and germinal tissue, always extended into the lateral ventricles. Cell proliferation, measured by Ki67 immunoreactivity, was suppressed bilaterally in germinal matrix and beyond from 8 hours to 7 days. Increased cell death was observed in the ipsilateral striatum and germinal matrix 1 and 2 days after PVH/IVH. Astrocyte and microglia reaction peaked at 2 days and persisted up to 28 days. Inflammatory response was minimal. Extravasated blood might play an important role in brain damage following PVH/IVH through suppression of cell proliferation.

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