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Neuroglial activation and Cx43 expression are reduced upon transplantation of human umbilical cord blood cells after perinatal hypoxic-ischemic injury.

Abstract：

:Glial cells play a crucial role in the pathomechanism of perinatal hypoxic-ischemic brain injury (HI) and are involved in the maintenance of a chronic state of inflammation that causes delayed neuronal damage. Activation of astrocytes is one factor prolonging brain damage and contributing to the formation of a glial scar that limits neuronal plasticity. In this context, the major astrocytic gap junction protein Connexin 43 (Cx43) has been ascribed various functions including regulation of astrocytic migration and proliferation. Here, we investigate glial responses like microglia/macrophages and astrocytic activation in a rat model of neonatal HI and characterize changes of these parameters upon transplantation of human umbilical cord blood cells (hUCB). As an alleviation of motor function in lesioned rats has previously been described in transplanted animals, we analyze the putative correlation between motor function and glial activation over time. The lesion-induced impairment of motor function, assessed by forelimb use bias, muscle strength and distal spasticity, was alleviated upon transplantation of hUCB short and long term. HI induced an acute inflammatory reaction with activation of microglia/macrophages and reactive astrogliosis associated with perilesional upregulation of Cx43 that slowly declined during the chronic post-ischemic phase. hUCB transplantation accelerated the regression of inflammatory events, narrowed the perilesional astrocytic wall and led to a downregulation of the investigated astrocytic proteins. Thus, in the immature brain, hUCB may indirectly reduce secondary cell death upon hypoxia-ischemia and facilitate post-ischemic plasticity through the attenuation of reactive gliosis. This article is part of a Special Issue entitled Electrical Synapses.

journal_name

Brain Res

journal_title

Brain research

authors

Wasielewski B,Jensen A,Roth-Härer A,Dermietzel R,Meier C

doi

10.1016/j.brainres.2012.05.066

subject

Has Abstract

pub_date

2012-12-03 00:00:00

pages

39-53

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(12)01151-1

journal_volume

1487

pub_type

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Neuroglial activation and Cx43 expression are reduced upon transplantation of human umbilical cord blood cells after perinatal hypoxic-ischemic injury.