A modified rehabilitation paradigm bilaterally increased rat extensor digitorum communis muscle size but did not improve forelimb function after stroke.

Malnutrition after stroke may lessen the beneficial effects of rehabilitation on motor recovery through influences on both brain and skeletal muscle. Enriched rehabilitation (ER), a combination of environmental enrichment and forelimb reaching practice, is used preclinically to study recovery of skilled reaching after stroke. However, the chronic food restriction typically used to motivate engagement in reaching practice is a barrier to using ER to investigate interactions between nutritional status and rehabilitation.

Liposomal Phytosterols as LDL-Cholesterol-Lowering Agents in Diet-Induced Hyperlipidemia.

The high blood level of low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease. Plant sterols, known as phytosterols (PSs), can reduce LDL-C in a range of 8-14%. The extent of LDL-C reduction depends on its formulation.

Preventing protein-energy malnutrition after cortical stroke enhances recovery of symmetry in forelimb use during spontaneous exploration.

Protein-energy malnutrition (PEM) commonly arises after stroke. We investigated the effects of preventing PEM on spontaneous recovery of forelimb use, infarct size, and the acute phase response in the chronic post-stroke period. Male, adult, Sprague-Dawley rats were acclimatized to control diet (12.

Protein-Energy Malnutrition Exacerbates Stroke-Induced Forelimb Abnormalities and Dampens Neuroinflammation.

Protein-energy malnutrition (PEM) pre-existing at stroke onset is believed to worsen functional outcome, yet the underlying mechanisms are not fully understood. Since brain inflammation is an important modulator of neurological recovery after stroke, we explored the impact of PEM on neuroinflammation in the acute period in relation to stroke-initiated sensori-motor abnormalities. Adult rats were fed a low-protein (LP) or normal protein (NP) diet for 28 days before inducing photothrombotic stroke (St) in the forelimb region of the motor cortex or sham surgery; the diets continued for 3 days after the stroke.

Parallel changes in cortical neuron biochemistry and motor function in protein-energy malnourished adult rats.

While protein-energy malnutrition in the adult has been reported to induce motor abnormalities and exaggerate motor deficits caused by stroke, it is not known if alterations in mature cortical neurons contribute to the functional deficits. Therefore, we explored if PEM in adult rats provoked changes in the biochemical profile of neurons in the forelimb and hindlimb regions of the motor cortex. Fourier transform infrared spectroscopic imaging using a synchrotron generated light source revealed for the first time altered lipid composition in neurons and subcellular domains (cytosol and nuclei) in a cortical layer and region-specific manner.

Rehabilitation Augments Hematoma Clearance and Attenuates Oxidative Injury and Ion Dyshomeostasis After Brain Hemorrhage.

Background And Purpose: We assessed the elemental and biochemical effects of rehabilitation after intracerebral hemorrhage, with emphasis on iron-mediated oxidative stress, using a novel multimodal biospectroscopic imaging approach.

Methods: Collagenase-induced striatal hemorrhage was produced in rats that were randomized to enriched rehabilitation or control intervention starting on day 7. Animals were euthanized on day 14 or 21, a period of ongoing cell death.

Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat.

Synchrotron-based X-ray fluorescence imaging (XFI) of zinc (Zn) has been recently implemented to understand the efficiency of various therapeutic interventions targeting post-stroke neuroprotection and neuroplasticity. However, it is uncertain if micro XFI can resolve neuroplasticity-induced changes. Thus, we explored if learning-associated behavioral changes would be accompanied by changes in cortical Zn concentration measured by XFI in healthy adult rats.

Imaging Taurine in the Central Nervous System Using Chemically Specific X-ray Fluorescence Imaging at the Sulfur K-Edge.

A method to image taurine distributions within the central nervous system and other organs has long been sought. Since taurine is small and mobile, it cannot be chemically "tagged" and imaged using conventional immuno-histochemistry methods. Combining numerous indirect measurements, taurine is known to play critical roles in brain function during health and disease and is proposed to act as a neuro-osmolyte, neuro-modulator, and possibly a neuro-transmitter.

Novel bio-spectroscopic imaging reveals disturbed protein homeostasis and thiol redox with protein aggregation prior to hippocampal CA1 pyramidal neuron death induced by global brain ischemia in the rat.

Global brain ischemia resulting from cardiac arrest and cardiac surgery can lead to permanent brain damage and mental impairment. A clinical hallmark of global brain ischemia is delayed neurodegeneration, particularly within the CA1 subsector of the hippocampus. Unfortunately, the biochemical mechanisms have not been fully elucidated, hindering optimization of current therapies (i.

Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats.

Background: Adult protein-energy malnutrition (PEM) often occurs in combination with neurological disorders affecting hand use and walking ability. The independent effects of PEM on motor function are not well characterized and may be obscured by these comorbidities.

Objective: Our goal was to undertake a comprehensive evaluation of sensorimotor function with the onset and progression of PEM in an adult male rat model.

Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model.

Background: The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability.

A new method to image heme-Fe, total Fe, and aggregated protein levels after intracerebral hemorrhage.

An intracerebral hemorrhage (ICH) is a devastating stroke that results in high mortality and significant disability in survivors. Unfortunately, the underlying mechanisms of this injury are not yet fully understood. After the primary (mechanical) trauma, secondary degenerative events contribute to ongoing cell death in the peri-hematoma region.

In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain.

Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation.

Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied.

Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex.

Protein-energy malnutrition induces an aberrant acute-phase response and modifies the circadian rhythm of core temperature.

Protein-energy malnutrition (PEM), present in 12%-19% of stroke patients upon hospital admission, appears to be a detrimental comorbidity factor that impairs functional outcome, but the mechanisms are not fully elucidated. Because ischemic brain injury is highly temperature-sensitive, the objectives of this study were to investigate whether PEM causes sustained changes in temperature that are associated with an inflammatory response. Activity levels were recorded as a possible explanation for the immediate elevation in temperature upon introduction to a low protein diet.

Subcellular biochemical investigation of purkinje neurons using synchrotron radiation fourier transform infrared spectroscopic imaging with a focal plane array detector.

Coupling Fourier transform infrared spectroscopy with focal plane array detectors at synchrotron radiation sources (SR-FTIR-FPA) has provided a rapid method to simultaneously image numerous biochemical markers in situ at diffraction limited resolution. Since cells and nuclei are well resolved at this spatial resolution, a direct comparison can be made between FTIR functional group images and the histology of the same section. To allow histological analysis of the same section analyzed with infrared imaging, unfixed air-dried tissue sections are typically fixed (after infrared spectroscopic analysis is completed) via immersion fixation.

X-ray absorption spectroscopy at the sulfur K-edge: a new tool to investigate the biochemical mechanisms of neurodegeneration.

Sulfur containing molecules such as thiols, disulfides, sulfoxides, sulfonic acids, and sulfates may contribute to neurodegenerative processes. However, previous study in this field has been limited by the lack of in situ analytical techniques. This limitation may now be largely overcome following the development of synchrotron radiation X-ray absorption spectroscopy at the sulfur K-edge, which has been validated as a novel tool to investigate and image the speciation of sulfur in situ.

Iron deficiency anemia prevalence at first stroke or transient ischemic attack.

Background: Iron deficiency anemia (IDA) has been implicated in the etiology of transient ischemic attack and ischemic stroke. This study aimed to: 1) document IDA prevalence in patients ≥ 65 years of age admitted to hospital with transient ischemic attack or first ischemic stroke, and 2) investigate dietary intake as a predictor of iron status.

Methods: Ninety-four patients were enrolled.

Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem.

Protein-energy malnutrition alters thermoregulatory homeostasis and the response to brain ischemia.

Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery.

Protein-energy malnutrition alters hippocampal plasticity-associated protein expression following global ischemia in the gerbil.

Previously it has been demonstrated that protein-energy malnutrition (PEM) impairs habituation in the open field test following global ischemia. The present study examined the hypothesis that PEM exerts some of its deleterious effects on functional outcome by altering the post-ischemic expression of the plasticity-associated genes brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-related kinase B (trkB), and growth-associated protein-43 (GAP-43). Male, Mongolian gerbils (11-12 wk) were randomized to either control diet (12.

Protein-energy malnutrition increases activation of the transcription factor, nuclear factor kappaB, in the gerbil hippocampus following global ischemia.

Protein-energy malnutrition (PEM) exacerbates functional impairment caused by brain ischemia. This is correlated with reactive gliosis, which suggests an increased inflammatory response. The objective of the current study was to investigate if PEM increases hippocampal activation of nuclear factor kappaB (NFkappaB), a transcription factor that amplifies the inflammatory response involved in ischemic brain injury.

Can a reward-based behavioural test be used to investigate the effect of protein-energy malnutrition on hippocampal function?

Our laboratory is investigating the effects of protein-energy malnutrition (PEM) on cognitive outcome following global ischemia. Here, we investigated whether PEM independently impairs working memory in the T-maze and if the associated food reward reverses PEM. Gerbils were fed 12.

The FOOD Trial Collaboration: nutritional supplementation strategies and acute stroke outcome.

Results from three large, randomized, multicenter FOOD (Feed or Ordinary Food) Collaboration Trials showed no reduction in death or poor outcome with routine oral protein-energy supplementation of stroke patients who were primarily well nourished upon admission to the hospital. Nasogastric tube feeding was favored over percutaneous endoscopic gastrostomy as the early route of feeding in dysphagic stroke patients.