BackgroundTraumatic brain injury (TBI) is a global health concern that typically causes emotional disturbances and cognitive dysfunction. Secondary pathologies following TBI may be associated with chronic neurodegenerative disorders and an enhanced likelihood of developing dementia-like disease in later life. There are currently no approved drugs for mitigating the acute or chronic effects of TBI.MethodsThe effects of the drug pomalidomide (Pom), an FDA-approved immunomodulatory agent, were evaluated in a rat model of moderate to severe TBI induced by controlled cortical impact. Post-TBI intravenous administration of Pom (0.5 mg/kg at 5 or 7 h and 0.1 mg/kg at 5 h) was evaluated on functional and histological measures that included motor function, fine more coordination, somatosensory function, lesion volume, cortical neurodegeneration, neuronal apoptosis, and the induction of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).ResultsPom 0.5 mg/kg administration at 5 h, but not at 7 h post-TBI, significantly mitigated the TBI-induced injury volume and functional impairments, neurodegeneration, neuronal apoptosis, and cytokine mRNA and protein induction. To evaluate underlying mechanisms, the actions of Pom on neuronal survival, microglial activation, and the induction of TNF-α were assessed in mixed cortical cultures following a glutamate challenge. Pom dose-dependently ameliorated glutamate-mediated cytotoxic effects on cell viability and reduced microglial cell activation, significantly attenuating the induction of TNF-α.ConclusionsPost-injury treatment with a single Pom dose within 5 h significantly reduced functional impairments in a well-characterized animal model of TBI. Pom decreased the injury lesion volume, augmented neuronal survival, and provided anti-inflammatory properties. These findings strongly support the further evaluation and optimization of Pom for potential use in clinical TBI.

The seed of the plant Jatropha curcas contains a toxic protein, designated as curcin, which was purified to apparent homogeneity by the combined use of chromatography on Sephdex G-100. The molecular weight of 28.2 kDa and the pI of 8.54 were determined. The protein was found to be a glycoprotein; the total neutral-surge content was 4.91%. It strongly inhibits the protein synthesis of rabbit reticulocyte lysate, with an IC(50) of 0.42 nM. It was determined by Edman that the sequence of the N-terminal thirty-two amino acids was: A-G/Y-S/K-T/A-P/D-T-L-T-I-T-Y-D-A-T/A-A-D-K-K-N-Y-A-Q-F-I-K-D-L-R-E-A-F/A-G. The isolated curcin had a hemagglutinating activity, when its concentration was more than 7.8 mg/L. The secondary structure of curcin was analyzed by Circular Dichroism (CD) spectrum. The result shows the curcin contains alpha-helix (22.3%), beta-sheet (43.5%), and random coil and corner (34.2%). The results of acute toxicity in mice show that mice oral semi-lethal dose LD(50) was 104.737 +/- 29.447 mg/kg; mice parenteral semi-lethal dose LD(50) was 67.20 +/- 10.445 mg/kg.

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