Extract Derived from Rat Brains in the Acute Phase Following Traumatic Brain Injury Impairs Survival of Undifferentiated Stem Cells and Induces Rapid Differentiation of Surviving Cells

Abstract

Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and /or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro. Rats were sacrificed at t = 45 minutes following lateral fluid-percussion injury and extracts of cerebral tissue were prepared from 4-6 healthy or injured rat brain hemispheres. Murine embryonic stem cells (CGR8) cultured in serum-free medium were then conditioned for a week with HBE or TBE. Omission of serum from the culture medium induced neural differentiation of CGR8 stem cells, as indicated by a significant time dependent down-regulation of oct-4 with a concomitant upregulation of nestin after 7 days. In parallel cell loss was observed that seemed to be largely due to apoptotic cell death. In TBE treated cells, on the other hand, a significant amplification of apoptotic cell death, enhancement of nestin and MAP2 expression and marked morphological changes such as axonal-like outgrowth was observed within 3 days of conditioning. Treatment of stem cells with HBE resulted in less pronounced neuronal differentiation processes. Axonal-like outgrowth was not observed. Our data suggest that during the early acute phase of traumatic injury the cerebral environment is disposed to detrimental as well as potent protective signals that seem to rapidly induce neurogenic processes.

Metabolomics analysis of the hippocampus in a rat model of traumatic brain injury during the acute phase

“…Traumatic brain injury is a severe cranial injury induced by sudden external force. Generally, we take 1-3 days after onset of TBI as time points to explore the effects of experimental acute TBI (Bentz et al, 2010;Yang et al, 2019;Zhang et al, 2014). Generally, we take 1-3 days after onset of TBI as time points to explore the effects of experimental acute TBI (Bentz et al, 2010;Yang et al, 2019;Zhang et al, 2014).…”

The effect of fetal rat brain extract on morphology of bone marrow-derived mesenchymal stem cells

“…Furthermore, in a similar experiment, differentiation of BMMSCs to neurons, astrocytes, and glial cells were performed using mouse spinal extract (Jamous et al 2010). In addition, Bentz et al (2010) showed that some fractions of hippocampus, cerebellum, or cortex could form bipolar and multipolar phenotypes. Formation of cells with neural phenotypes from BM-MSCs had been demonstrated in several experiments (Abouelfetouh et al 2004;Kim et al 2007;Qian and Saltzman 2004).…”

Impurity of Stem Cell Graft by Murine Embryonic Fibroblasts – Implications for Cell-Based Therapy of the Central Nervous System

“…Various interactions between different cell types and the brain microenvironment were reported in several studies (Bentz et al, 2006, 2007, 2010; Molcanyi et al, 2007). We previously showed that incubation of ESCs with brain extract in vitro resulted in the release of neurotrophic factors, which was accompanied by the considerable co-production of these neurotrophins by inactivated co-cultured MEFs (Bentz et al, 2007).…”