Intracranial injection of recombinant stromal-derived factor-1 alpha (SDF-1α) attenuates traumatic brain injury in rats - PubMed (original) (raw)
Intracranial injection of recombinant stromal-derived factor-1 alpha (SDF-1α) attenuates traumatic brain injury in rats
Weifeng Sun et al. Inflamm Res. 2014 Apr.
Abstract
Objective: This study was conducted to investigate the role of stromal-derived factor-1 alpha (SDF-1α) in a secondary brain injury after traumatic brain injury (TBI) in rats, and to further elucidate its underlying regulatory mechanisms.
Materials and methods: Male Sprague-Dawley rats underwent TBI for 30 min, and then received intracranial injections of recombinant SDF-1α, SDF-1α antibody, or saline as a vehicle control. At 24 h after TBI, brain tissues from the experimental animals were subjected to histology, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and western blot analyses.
Results: TBI-induced brain edema and blood-brain barrier disruption were ameliorated by post-injury injections of SDF-1α. TBI-induced neuronal degradation and apoptosis, accompanied by increased cleaved caspase-3, cleaved PARP and Bax, and decreased Bcl-2 were found to be attenuated by SDF-1α injection. Nitric oxide (NO) and inducible nitric oxide synthase (iNOS) levels decreased in SDF-1α treated animals after TBI. SDF-1α repressed inflammatory responses by inhibiting the expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6. However, neutralizing the effect of SDF-1α with its antibody abolished these therapeutic alterations in TBI animals. Importantly, SDF-1α attenuated the brain lesion by affecting the ERK and NF-κB signaling pathways after mechanical head trauma in rats.
Conclusions: SDF-1α ameliorates mechanical trauma-induced pathological changes via its anti-apoptotic and anti-inflammatory action in the brain.
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