Pathogenesis and Prevention of Intraventricular Hemorrhage

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Key points

  • Pathogenesis of intraventricular hemorrhage (IVH) is ascribed to the intrinsic weakness of germinal matrix vasculature and to the fluctuation in the cerebral blood flow.

  • The germinal matrix displays accelerated angiogenesis, which orchestrates formation of nascent vessels that lack pericytes, display immature basal lamina low in fibronectin, and has astrocyte end-feet coverage deficient in glial fibrillary acidic protein. These morphologic and molecular factors contribute to the fragility of the

Pathogenesis of IVH

Pathogenesis of IVH is multifactorial, complex, and heterogeneous. An inherent fragility of the germinal matrix vasculature sets the ground for hemorrhage, and fluctuation in the cerebral blood flow induces the rupture of vasculature (Box 1). If there are associated platelet or coagulation disorders, the homeostasis mechanisms are impaired, which might accentuate the hemorrhage. Vaginal delivery, low Apgar score, severe respiratory distress syndrome, pneumothorax, hypoxia, hypercapnia,

Rationale of Preventive Therapies

Because IVH is primarily attributed to increased vascular fragility and disturbance in CBF, the strategies should be directed to strengthening the germinal matrix vasculature and to stabilizing the CBF. Germinal matrix has a subset of vessels that are angiogenic, immature, and lack pericytes, and they thrive because of high levels of VEGF and angiopoietin-2.13, 22 These blood vessels exhibit high fragility and propensity to bleed. It appears that the immature neovasculature are pruned within a

Summary

IVH is a major complication of prematurity. IVH usually initiates in the periventricular germinal matrix and progresses to IVH on the rupture of the underlying ependyma. The pathogenesis of IVH is ascribed to the intrinsic fragility of germinal matrix vasculature and to fluctuations in the CBF. The germinal matrix exhibits accelerated angiogenesis, which orchestrates formation of nascent vessels that lack pericytes, display immature basal lamina low in fibronectin, and have astrocyte end-feet

Acknowledgments

Authors thank Drs Laura Ment and Barabara Stonstreet for the critical review of the article and Joanne Abrahams for the assistance with images.

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    Source of Funding: NIH/NINDS grant RO1 NS071263.

    Conflict of Interest: None.

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