Ideal treatment in Parkinson's disease (PD) aims at relieving symptoms and slowing disease progression. Of all remedies, levodopa remains the most effective for symptomatic relief, but the medical need for neuroprotectant drugs is still unfulfilled. Safinamide, currently in phase III clinical trials for the treatment of PD, is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model. Safinamide potentiates levodopa-mediated increase of DA levels in DA-depleted mice and reverses the waning motor response after prolonged levodopa treatment in 6-OHDA-lesioned rats. Safinamide has excellent bioavailability, linear kinetics, and is suitable for once-a-day administration. Therefore, safinamide may be used in PD to reduce l-dopa dosage and also represents a valuable therapeutic drug to test disease-modifying potential.

Background Environmental enrichment (EE) enhances motor and cognitive performance after traumatic brain injury (TBI). However, whether the EE-mediated benefits are time-dependent and task-specific is unclear. A preliminary study, in which only half of the possible temporal manipulations were evaluated, revealed that the beneficial effects of enrichment were only observed when provided concurrently with specific training (i.e., motor or cognitive), suggesting task-specific dependence. Objective To further assess the effects of time of initiation and duration of EE on neurobehavioral recovery after TBI by evaluating and directly comparing all the temporal permutations. Methods Anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to eight groups receiving continuous, or early and delayed EE with either 1 or 2 weeks of exposure. Functional outcome was assessed with established motor (beam-balance/walk) and cognitive (Morris water maze) tests on post-injury days 1-5 and 14-18, respectively. Results Motor ability was enhanced in the TBI groups that received early EE (i.e., during testing) vs. standard housing. In contrast, acquisition of spatial learning was facilitated in the groups receiving delayed EE (i.e., during training). Conclusions These data support the conclusion from the previous study that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience, and extends those preliminary findings by demonstrating that the duration of enriched exposure is also important for functional recovery.

Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. Motor function was assessed with beam-balance/beam-walk and rotarod tasks on post-operative days 1–5 and every other day from 1–19, respectively. Spatial learning/memory was evaluated in a Morris water maze on days 14–19. Morphologically intact hippocampal CA 1/3 cells and cortical lesion volume were quantified 3 weeks after injury. No differences were observed between the EE and STD sham groups in any endpoint measure and thus the data were pooled. In the TBI groups, EE improved beam-balance, beam-walk, rotarod, and spatial learning performance vs. STD (p’s < 0.05). EE also provided significant histological protection as confirmed by increased CA1/3 cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation.

Insulin-like growth factor 1 (IGF-1) plays a critical role in CNS development. IGF-1 can block neuronal apoptosis in vitro and in vivo. IGF-1 is thought to be cleaved into des-N-(1-3)-IGF-1 and an amino terminal glycine-proline-glutamate (GPE tripeptide). Here we report a neuroprotective role for GPE tripeptide, with enhanced survival of the CA1-2 hippocampal neurons following an excitotoxic insult in vitro. Binding and displacement studies suggest uniquely distributed sites of action within the rat including the hippocampal CA1-2, pyriform cortex, amygdala, choroid plexus, blood vessels and to a lesser extent in the cortical regions. A similar pattern of binding was seen in the human. This finding could lead to new strategies to reduce neuronal death after injury and in disease.

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