What is the central question of this study? Can the
neuroprotective agent curcumin affect restorative action of neural stem/progenitor cells in the injured rat brain? What is the main finding and its importance? In the presence of
curcumin,
transplantation of neural stem/progenitor cells in the context of
PuraMatrix reduced lesion size and reactive inflammatory responses, and boosted survival rate of grafted neurons. In addition it improved the neurological status of injured animals. This could be beneficial in designing new therapeutic approaches for
brain injury based on this combination
therapy.
ABSTRACT:
Traumatic brain injury (TBI) is catastrophic neurological damage associated with substantial morbidity and mortality. To date, there is no specific treatment for restoring lost brain tissue. In light of the complex pathology of
brain injury, the present study evaluated the effects of combination
therapy using autologous neural stem/progenitor cells (NS/PCs),
PuraMatrix (PM) and
curcumin in an animal model of
brain injury. After stereotactic biopsy of subventricular zone tissue and culture of NS/PCs, 36 male Wistar rats (150-200 g) were randomly divided into six groups receiving
dimethyl sulfoxide (
DMSO), curcumin (100 mg kg-1 in
DMSO), PM + curcumin (100 mg kg-1 in
DMSO), NS/PCs + curcumin (100 mg kg-1 in
DMSO), NS/PCs + PM +
curcumin (100 mg kg-1 in
DMSO) and NS/PCs + PM +
curcumin (1 µm) following
acute brain injury. The animals were evaluated in term of neurological status for 4 weeks, then decapitated. Nissl and TUNEL staining and immunohistochemistry for
bromodeoxyuridine,
glial fibrillary acidic protein, doublecortin, Map2, Olig2, Iba1 and CD68 were performed. We found that combination
therapy by NS/PCs + PM + curcumin reduced the lesion size,
astrogliosis, macrophage and microglial reaction as well as the number of apoptotic cells. Moreover, the transplanted cells were able to survive and differentiate after 4 weeks. Besides these findings,
transplantation of NS/PCs in the context of PM and
curcumin improved the neurological status of injured animals. In conclusion, our data suggest that this combination
therapy can be beneficial in developing future therapeutic approaches for
brain injury.