Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier

Cesario V. Borlongan; Jeffrey G. Lind; Ora Dillon-Carter; Guolong Yu; Martin Hadman; Charles Cheng; James Carroll; David C. Hess

doi:10.1016/j.brainres.2004.02.050

Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier

Cesario V. Borlongan, Jeffrey G. Lind, Ora Dillon-Carter, Guolong Yu, Martin Hadman, Charles Cheng, James Carroll, David C. Hess

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.

Original language	English (US)
Pages (from-to)	26-33
Number of pages	8
Journal	Brain Research
Volume	1009
Issue number	1-2
DOIs	https://doi.org/10.1016/j.brainres.2004.02.050
State	Published - May 29 2004

Keywords

Cross-species
Development and regeneration
Immunosuppression
Neural transplantation
Neuroprotection
Stem cell
Striatum
Transplantation

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2004.02.050

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title = "Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier",

abstract = "We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.",

keywords = "Cross-species, Development and regeneration, Immunosuppression, Neural transplantation, Neuroprotection, Stem cell, Striatum, Transplantation",

author = "Borlongan, {Cesario V.} and Lind, {Jeffrey G.} and Ora Dillon-Carter and Guolong Yu and Martin Hadman and Charles Cheng and James Carroll and Hess, {David C.}",

note = "Funding Information: CVB is supported by VA VISN7 Career Development Award and AHA Southeast Affiliate Grant-In-Aid 0355225B; JC by NIH grant R21-NS43439-01; DCH by VA Merit Review and NIH R21-NS43487-01. The authors thank Dr. Michael Chopp for his valuable critique.",

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AU - Borlongan, Cesario V.

AU - Lind, Jeffrey G.

AU - Dillon-Carter, Ora

AU - Yu, Guolong

AU - Hadman, Martin

AU - Cheng, Charles

AU - Carroll, James

AU - Hess, David C.

N1 - Funding Information: CVB is supported by VA VISN7 Career Development Award and AHA Southeast Affiliate Grant-In-Aid 0355225B; JC by NIH grant R21-NS43439-01; DCH by VA Merit Review and NIH R21-NS43487-01. The authors thank Dr. Michael Chopp for his valuable critique.

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N2 - We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.

AB - We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.

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KW - Development and regeneration

KW - Immunosuppression

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KW - Striatum

KW - Transplantation

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ER -

Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier

Abstract

Keywords

ASJC Scopus subject areas

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