development-of-a-3d-graphene-electrode-dielectrophoretic-device

Development of a 3D Graphene Electrode Dielectrophoretic Device

The design and fabrication of a novel 3D electrode microdevice using 50 &#181;m thick graphene paper and 100 &#181;m double sided tape is described. The ...

Michigan Technological University

External stimuli, including environmental enrichment (EE) and physical activity, have been shown to significantly facilitate recovery from brain injury. However, whether EE can be used as a preconditioning method to induce cerebral ischemic tolerance has never been investigated. Furthermore, whether, and to what extent, such environmental stimuli regulate physical activity to promote neuroprotection is largely unclear. To examine the neuroprotective effects of pre-ischemic EE (PIEE) and to investigate the relationship between these effects and EE-induced physical activity, we tested neurobehavioral and morphological recovery of rats following transient focal cerebral ischemia. Our study showed that PIEE improved the recovery of motor function, spatial learning and memory without reduction in brain edema or infarct volume. We also found that PIEE robustly increased the level of physical activity of rats that positively correlated with the extent of neurobehavioral recovery. Our results suggest that PIEE may induce brain ischemic tolerance through, at least partially, increasing physical activity.

Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase.

Enriched environments (EE) have been used for a long time to promote recovery in many neurological disorders, however, a growing body of inconsistent results strongly calls for a rigorous standardization of experimental EE paradigms. Although some core principles are well accepted as standards, a method to quantitatively assess the complexity of EE in various experimental designs is still lacking. In this study, we tracked and recorded the physical exercise of rats in four housing conditions, namely isolated condition, social condition, novel condition and EE. Then, we analyzed whether and to what extent, enrichment-induced exercise reflected the degree of enrichment. We next examined rat exercise in a conventional environment condition and under different light intensities, to explore whether environment-related exercise could be considered a parameter to quantify the degree of enrichment. The results obtained showed that (1) both inanimate and social stimulations enhanced the exercise level and (2) EE combined the effects of the two stimulations. Furthermore, exercise durability which correlated positively with degree of enrichment, was an objective measure of different housing conditions. Exercise-related parameters also sensitively reflected the impacts of light intensity even in the same enrichment arrangements. Our results indicate that there is a direct and measurable correlation between degree of environmental enrichment and enrichment-induced exercise, and therefore enrichment-induced exercise could be used as a helpful tool to evaluate the degree of housing conditions and to standardize the EE protocols.

Enrichment-induced exercise to quantify the effect of different housing conditions: a tool to standardize enriched environment protocols.

This study examined whether very early initiated physical rehabilitation (VEIPR), as a recommended therapy for postischemia, could improve motor performance and cerebral blood flow (CBF). Adult male rats with ischemic injury caused by middle cerebral artery occlusion (MCAO) were trained to run on a treadmill for 30min per day at 12m/min. Through such exercise training for 3 days, the ischemic rats exhibited increased motor function and decreased infarct volume, as measured by a behavioral score and 2,3,5-triphenyltetrazolium chloride (TTC) staining method, as well as accelerated CBF, as detected with laser speckle imaging (LSI). Furthermore, to determine whether the observed improved CBF provided the protective factor for motor function recovery, we investigated the apoptosis of ischemic rat brain microvascular endothelial cells (rBMECs), which accepted the mechanical force of CBF directly, under flow intervention. The findings indicated that a modest flow decreased cell apoptosis in the ischemic condition and that this effect is magnitude dependent, as excessive flow increased apoptosis.

Early exercise training improves ischemic outcome in rats by cerebral hemodynamics.

Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury is neuroprotective in animal models. However, little is known about of the neuroprotective effects of EE exposure prior to injury. The current study examined the effects of prior EE exposure on inducible and neuronal nitric oxide syntheses (iNOS and nNOS) after transient middle cerebral artery occlusion (tMCAO) in rats. A total of 72 rats were exposed to EE or standard housing condition (SC) for 1 month, followed by 90-min MCAO and reperfusion or sham surgery, leading to the following three groups: (1) EE+MCAO (n=24), (2) SC+MCAO (n=24), (3) SC+sham (n=24). Rats were sacrificed at 1, 6, or 24h after MCAO (n=6/group) for iNOS and nNOS mRNA quantification by real-time PCR and at 24h after MCAO (n=6/group) for iNOS and nNOS protein quantification by Western blot or were evaluated for neurological function outcomes, then sacrificed to assess infarct volume (n=6/group). Results showed that prior exposure to EE reduced iNOS and nNOS mRNA and protein and improved neurological status after MCAO without affecting infarct volume, suggesting that EE may provide neuroprotection via ischemic preconditioning.

Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats.

Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury is neuroprotective in animal models. Recent studies have demonstrated that animals housed in an enriched environment condition after an experimental stroke obtained a better functional outcome than those housed in a standard condition. However, little is known about the underlying mechanisms of neuroprotective effects of enriched environment exposure prior to injury. The current study examined the neuroprotective effects of prior enriched environment exposure after transient middle cerebral artery occlusion (MCAO) in rats. Male Sprague Dawley (SD) rats, weighing 55-65g at the beginning of the experiment, were randomly assigned to a pre-ischemic enriched environment (PIEE) or pre-ischemic standard condition (PISC) group for 1 month. They were weighed on days1, 7, 18, and 28, and their locomotor activity was tracked during the period between 9:00am and 3:00pm daily. After 1 month, ischemia was induced by occluding the middle cerebral artery for 90min, followed by reperfusion. After approximately 24h of the operation, functional outcomes were assessed using the beam-walking test and a neurological evaluation scale in all rats. We measured the expression of extracellular signal regulated protein kinases1/2 (ERK1/2) by western blotting and gene expression levels of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthasen (iNOS) by Real-Time PCR in the cortical area affected by ischemia. Finally, we measured the level of malondialdehyde (MDA) content, which is a biomarker of oxidative stress. The results showed that rats in the PIEE group had lighter weight than those in the PISC group. The functional outcomes of rats in the PIEE group were better than those in the PISC group, and substances associated with inflammation, such as MDA, nNOS, iNOS, and phospho-ERK1/2, were lower in the PIEE group compared with the PISC group. These results indicate that enriched environment may provide neuroprotection via ischemic preconditioning and enhance resilience to cerebral ischemia.

Article	Year
Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase. Brain research\| PubMed ID: 23501217	2013
Enrichment-induced exercise to quantify the effect of different housing conditions: a tool to standardize enriched environment protocols. Behavioural brain research\| PubMed ID: 23624191	2013
Early exercise training improves ischemic outcome in rats by cerebral hemodynamics. Brain research\| PubMed ID: 23948104	2013
Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats. Neurotoxicology\| PubMed ID: 24055239	2013
Neuroprotective effects of prior exposure to enriched environment on cerebral ischemia/reperfusion injury in rats: the possible molecular mechanism. Brain research\| PubMed ID: 24084470	2013

Hongyu Xie

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