Axonal injury after TBI can be reliably quantified using plasma NfL, which predicts long-term functional outcomes and progressive neurodegeneration.

Background: While supportive treatment for traumatic brain injury (TBI) has progressed, specific neuroprotective interventions are still lacking. Models of ischaemic heart and brain injury show a therapeutic potential for Argon gas, but it is still not known whether inhaled Argon (iAr) is protective in TBI. We tested the effects of iAr administered acutely to TBI mice on brain oedema, tissue microenvironmental changes, neurological functions and structural outcome.Methods: Anaesthetized adult C57BL/6J mice were subjected to severe TBI by controlled cortical impact. Ten minutes after TBI, mice were randomized to 24h treatment with iAr 70%-O2 30% or air (iCtr). Sensorimotor deficits were evaluated up to six weeks post-TBI by three independent tests.Cognitive function was evaluated by Barnes maze test at four weeks. Magnetic resonance imaging (MRI) was done to examine brain oedema at three days and white matter damages at five weeks.Microglia/macrophage activation and functional commitment was evaluated at one week after TBI by immunohistochemistry.Results: iAr significantly accelerated sensorimotor recovery and improved cognitive deficits one month after TBI, with less white matter damage in the ipsilateral fimbria and body of the corpus callosum. Early changes underpinning protection included a reduction of pericontusional vasogenic oedema and action on the inflammatory response. iAr significantly reduced microglial activation with increases in ramified cells and the M2-like marker YM1. Conclusion: iAr accelerates recovery of sensorimotor function and improves cognitive and structural outcome one-month after severe TBI in mice. Early effects include a reduction of brain oedema and neuroinflammation in the contused tissue.

Brain-derived neurotrophic factor (BDNF) dynamic changes were investigated in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) during use and the early phases of cocaine abstinence after 14 sessions (2 h self-administration/d; 0.25 mg/0.1 ml.6 s infusion) by employing a 'yoked control-operant paradigm'. The effect on BDNF was region-specific and dependent on the withdrawal time. In the NAc, BDNF protein levels increased immediately after the last self-administration session, with a larger increase in passively cocaine-exposed rats. In the mPFC, BDNF expression was elevated 24 h after the last self-administration session, independently of how the drug was encountered. No changes were found in NAc and mPFC 7 d after the last self-administration session. Analysis of transcript levels in the mPFC indicated that action on exon I might contribute to BDNF's cortical induction. These findings indicate a finely tuned modulation of BDNF expression during use and early phases of cocaine abstinence.

Chronic self-administration of nicotine induces maladaptive changes in the cortico-accumbal glutamate (Glu) network. Consequently, re-exposure to nicotine-associated cues raises extracellular Glu in the nucleus accumbens reinstating drug-seeking. Restoring basal concentrations of extracellular Glu, thereby increasing tonic activation of the presynaptic group II metabotropic Glu receptors (mGluR2/3) with N-acetylcysteine (N-AC), might offer a valid therapeutic approach for maintaining smoking abstinence. Although N-AC modulates nicotine-seeking behavior by drug-associated stimuli in abstinent rats, it is still unclear whether it occurs through activation of mGluR2/3. Male Wistar rats were trained to associate discriminative stimuli (S s) with the availability of intravenous nicotine (0.03 mg/kg/65 µl/2-second/infusion) or oral saccharin (100 µl of 50 mg/l) self-administration versus non-reward. Reinforced response was followed by a cue signaling 20-second time-out (CSs). Once the training criterion was met, rats underwent lever press extinction, without reinforcers, S s and CSs. Re-exposure to nicotine or saccharin S /CS , but not non-reward S /CS , revived responding on the previously reinforced lever. Acute N-AC, 100 but not 60 or 30 mg/kg i.p., reduced cue-induced nicotine-seeking. N-AC 100 mg/kg did not modify cue-induced saccharin-seeking behavior or influenced locomotor activity. Blocking mGluR2/3 with the selective antagonist LY341495, 1 mg/kg i.p., completely prevented the antirelapse activity of N-AC. The finding that N-AC prevents cue-induced nicotine-seeking by stimulating mGluR2/3 might indicate a therapeutic opportunity for acute cue-controlled nicotine-seeking. Future studies could evaluate the persistent effects of chronic N-AC in promoting enduring suppression of nicotine-cue conditioned responding.