Articles: traumatic-brain-injuries.
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Experimental neurology · Nov 2013
Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent cognitive and memory deficits in a rat model of mild traumatic brain injury.
Traumatic brain injury (TBI) differs in severity from severe to mild. This study examined whether a combination of the drugs minocycline (MINO) plus N-acetylcysteine (NAC) produces behavioral and histological improvements in a mild version of the controlled cortical impact model of TBI (mCCI). Following mCCI, rats acquired an active place avoidance task by learning the location of a stationary shock zone on a rotating arena. ⋯ MINO plus NAC acted synergistically to increase Iba-1 expression since MINO alone suppressed expression and NAC alone had no effect. Despite the known anti-inflammatory actions of the individual drugs, MINO plus NAC appeared to modulate, rather than suppress neuroinflammation. This modulation of neuroinflammation may underlie the synergistic improvement in memory and set-shifting by the drug combination after mCCI.
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Neuroscience letters · Oct 2013
Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury.
Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. ⋯ Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI.
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Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. ⋯ Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand.
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Progranulin (PGRN) is known to play a role in the pathogenesis of neurodegenerative diseases. Recently, it has been demonstrated that patients with the homozygous mutation in the GRN gene present with neuronal ceroid lipofuscinosis, and there is growing evidence that PGRN is related to lysosomal function. In the present study, we investigated the possible role of PGRN in the lysosomes of activated microglia in the cerebral cortex after traumatic brain injury (TBI). ⋯ S6K1 phosphorylation in KO mice was significantly lower than that in WT mice. In addition, the number of nissl-positive and fluoro-jade B-positive cells around the injury was significantly decreased and increased, respectively, in KO as compared with WT mice. These results suggest that PGRN localized in the lysosome is involved in the activation of mTORC1, and its deficiency leads to increased TFEB nuclear translocation with a resultant increase in lysosomal biogenesis in activated microglia and exacerbated neuronal damage in the cerebral cortex after TBI.