Brain research
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The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. ⋯ CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug.
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Traumatic brain injury (TBI) is one of the largest health problems in the United States and affects both cognitive and motor function. Although weakness is common in TBI patients, few studies have demonstrated a reduction in strength in models of brain injury. ⋯ Following CCI, volitional forelimb strength is reduced by 36% and remains significantly reduced after 6 weeks of post-lesion training. We also show that CCI results in impairment of multiple additional measures of forelimb function for several weeks post-injury.
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Neurological complications contribute largely to the morbidity and mortality in patients with acute renal failure. In order to study pathophysiological complications of renal failure, a murine model of renal ischemia/reperfusion-induced acute kidney injury (AKI) was generated by 60min bilateral ischemia, and followed by 2h or 24h reperfusion (B-60'IRI). Compared to the sham-operated mice, B-60'IRI mice exhibited a significant inflammatory injury to remote brain. ⋯ The technology of cDNA microarray and quantitated RT-PCR are used to identify hippocampal genes whose expression is altered in response to AKI in B-60' IRI mice. The initiation of transcriptional abnormality was indicated by the finding that B-60' IRI mice exhibited upregulated mRNA levels of genes involved in inflammation, cell signaling, extracellular matrix and cell-cycle regulation and downregulated mRNA levels of genes involved in transporters, G protein-coupled receptor signaling, cell survival and chaperone. Our data suggest that renal IR contributes to a complicated hippocampal gene irregulation in inflammation and physiological homeostasis.
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mild traumatic brain injury (mTBI) can produce lasting memory deficits even in the absence of cell loss. We investigated changes in hippocampal firing patterns during exploration and during a novel object recognition (NOR) task. ⋯ memory deficits after mTBI are associated with decreased intrinsic burst activity and impaired context-specific firing patterns in the hippocampus during object exploration.
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A secondary and often lethal consequence of traumatic brain injury is cellular edema that we posit is due to astrocytic swelling caused by transmembrane water fluxes augmented by vasopressin-regulated aquaporin-4 (AQP4). We therefore tested whether vasopressin 1a receptor (V1aR) inhibition would suppress astrocyte AQP4, reduce astrocytic edema, and thereby diminish TBI-induced edematous changes. V1aR inhibition by SR49059 significantly reduced brain edema after cortical contusion injury (CCI) in rat 5h post-injury. ⋯ In CCI-vehicle, sham and CCI-SR49059 groups, fluorescence intensity of GFAP was 349±38, 56±5, and 244±30, respectively, V1aR was 601±71, 117.8±14, and 390±76, and AQP4 was 818±117, 158±5, and 458±55 (n=3/group). The results support that edema was predominantly cellular following CCI and documented that V1aR inhibition with SR49059 suppressed injury-induced up regulation of GFAP, V1A and AQP4, blunting edematous changes. Our findings suggest V1aR inhibitors may be potential therapeutic tools to prevent cellular swelling and provide treatment for post-traumatic brain edema.