Experimental neurology
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Experimental neurology · Mar 2015
Gap junction blockers attenuate beta oscillations and improve forelimb function in hemiparkinsonian rats.
Parkinson's disease (PD) is a neurodegenerative disease characterized by akinesia, bradykinesia, resting tremors and postural instability. Although various models have been developed to explain basal ganglia (BG) pathophysiology in PD, the recent reports that dominant beta (β) oscillations (12-30Hz) in BG nuclei of PD patients and parkinsonian animals coincide with motor dysfunction has led to an emerging idea that these oscillations may be a characteristic of PD. Due to the recent realization of these oscillations, the cellular and network mechanism(s) that underlie this process remain ill-defined. ⋯ Finally, we systemically injected CBX (200mg/kg) into hemiparkinsonian rats which attenuated dominant β oscillations in the right GPe and also improved left forepaw akinesia in the step test. Conversely, direct injection of TMA into the right GPe of naive rats induced contralateral left forelimb akinesia. Overall, our results suggest that GJs contribute to β oscillations in the GPe of hemiparkinsonian rats.
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Experimental neurology · Mar 2015
Hyperbaric oxygen preconditioning attenuates hemorrhagic transformation through increasing PPARγ in hyperglycemic MCAO rats.
Hyperbaric oxygen preconditioning (HBO-PC) has been demonstrated to attenuate hemorrhagic transformation (HT) after middle cerebral artery occlusion (MCAO) in hyperglycemic rats. However, the mechanisms remain to be illustrated. Recently, HBO-PC has been shown to activate peroxisome proliferator-activated receptor-gamma (PPARγ) by increasing 15d-PGJ2 in primary cultured neurons. ⋯ The levels of 15d-PGJ2, PPARγ, TNF-α and IL-1β, tight junction proteins as well as the activity of MMP-2 and MMP-9 were evaluated 24h after MCAO. HBO-PC reduced HT, improved neurological function, down-regulated inflammatory molecules and inhibited the activation of MMP-9 by increasing 15d-PGJ2 and PPARγ at 24h after MCAO. The results suggested that HBO-PC might be an alternative measure to decrease HT in ischemic stroke.
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Experimental neurology · Mar 2015
Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.
Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. ⋯ Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.
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Experimental neurology · Feb 2015
Nrf2-ARE activator carnosic acid decreases mitochondrial dysfunction, oxidative damage and neuronal cytoskeletal degradation following traumatic brain injury in mice.
The importance of free radical-induced oxidative damage after traumatic brain injury (TBI) has been well documented. Despite multiple clinical trials with radical-scavenging antioxidants that are neuroprotective in TBI models, none is approved for acute TBI patients. As an alternative antioxidant target, Nrf2 is a transcription factor that activates expression of antioxidant and cytoprotective genes by binding to antioxidant response elements (AREs) within DNA. ⋯ This was accompanied by decreased oxidative damage to mitochondrial proteins, suggesting the mechanistic connection of the two effects. Lastly, delaying the initial administration of CA up to 8h post-TBI was still capable of reducing cytoskeletal breakdown, thereby demonstrating a clinically relevant therapeutic window for this approach. This study demonstrates that pharmacological Nrf2-ARE induction is capable of neuroprotective efficacy when administered after TBI.
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Experimental neurology · Feb 2015
Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury.
Transplantation of neural progenitor cells (NPCs) may be a potential treatment strategy for traumatic brain injury (TBI) due to their intrinsic advantages, including the secretion of neurotrophins. Neurotrophins are critical for neuronal survival and repair, but their clinical use is limited. In this study, we hypothesized that pericontusional transplantation of NPCs genetically modified to secrete a synthetic, human multineurotrophin (MNTS1) would overcome some of the limitations of traditional neurotrophin therapy. ⋯ Transplant recipients exhibited escape latencies approximately half that of injured vehicle controls. While we observed greater transplant survival and neuronal differentiation of MNTS1-NPCs, our collective findings suggest that MNTS1 may be superfluous in terms of preserving the cytoarchitecture and rescuing behavioral deficits given the lack of significant difference between MNTS1- and GFP-control transplanted groups. Nevertheless, our overall findings support the potential of syngeneic NPC transplantation to enhance endogenous neuroreparative responses and may therefore be an effective treatment for TBI.