Bone Marrow to Brain in Neonatal Hypoxic-Ischemic injury

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Recent studies show that bone
marrow-derived stem cells differentiate into microglia, astrocytes, and
neurons. A variety of preparations, including crude bone marrow, marrow stromal
cells, and hematopoietic stem cells have been used for transplantation into
animal models. Brain injury may enhance this differentiation. We plan to
compare the potential of different bone marrow preparations to differentiate
into brain cells in a mouse model of neonatal hypoxic-ischemic (HI) injury. Our
hypothesis is that undifferentiated bone marrow assists in recovery from this
injury by the contribution of cells which differentiate into cerebral
endothelial cells, astrocytes, oligodendrocytes, and neurons.

Our specific aims are: 1) determine the expression of neural and endothelial
markers in cells arising from exogenous bone marrow preparations in injured
brain of the bone marrow recipient, and 2) determine if bone marrow-derived
cells develop into functioning neurons and glial cells after HI injury.

In this proposal we will deliver the HI injury to female mice on the seventh
postnatal day. At eight weeks of age, they will undergo irradiation and receive
bone marrow transplants from male mice of the same strain, some transgenic for
Green Fluorescent Protein (GFP). The cells for transplantation will be prepared
as crude marrow, marrow stromal cells or hematopoietic stem cells. The animals
will be sacrificed at intervals after the transplant for immunohistochemical
assessment of the male (Y chromosome) and GFP cells resulting in brain,
followed by electrophysiologic testing of the GFP cells.

This proposal satisfies the aims of the R21 model. We plan to obtain
preliminary data for a future proposal which will deal with methods of
enhancing bone marrow-derived cells in brain. Also, the proposal undertakes the
novel use of a neonatal injury model, with the animals treated at a later age.
This approach mimics what would occur in a clinical situation.
StatusNot started