Elemental characterisation of the pyramidal neuron layer within the rat and mouse hippocampus.

A unique combination of sensitivity, resolution, and penetration make X-ray fluorescence imaging (XFI) ideally suited to investigate trace elemental distributions in the biological context. XFI has gained widespread use as an analytical technique in the biological sciences, and in particular enables exciting new avenues of research in the field of neuroscience. In this study, elemental mapping by XFI was applied to characterise the elemental content within neuronal cell layers of hippocampal sub-regions of mice and rats. Although classical histochemical methods for metal detection exist, such approaches are typically limited to qualitative analysis. Specifically, histochemical methods are not uniformly sensitive to all chemical forms of a metal, often displaying variable sensitivity to specific "pools" or chemical forms of a metal. In addition, histochemical methods require fixation and extensive chemical treatment of samples, creating the strong likelihood for metal redistribution, leaching, or contamination. Direct quantitative elemental mapping of total elemental pools, in situ within ex vivo tissue sections, without the need for chemical fixation or addition of staining reagents is not possible with traditional histochemical methods; however, such a capability, which is provided by XFI, can offer an enormous analytical advantage. The results we report herein demonstrate the analytical advantage of XFI elemental mapping for direct, label-free metal quantification, in situ within ex vivo brain tissue sections. Specifically, we definitively characterise for the first time, the abundance of Fe within the pyramidal cell layers of the hippocampus. Localisation of Fe to this cell layer is not reproducibly achieved with classical Perls histochemical Fe stains. The ability of XFI to directly quantify neuronal elemental (P, S, Cl, K, Ca, Fe, Cu, Zn) distributions, revealed unique profiles of Fe and Zn within anatomical sub-regions of the hippocampus i.e., cornu ammonis 1, 2 or 3 (CA1, CA2 or CA3) sub-regions. Interestingly, our study reveals a unique Fe gradient across neuron populations within the non-degenerating and pathology free rat hippocampus, which curiously mirrors the pattern of region-specific vulnerability of the hippocampus that has previously been established to occur in various neurodegenerative diseases.

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis.

Plasticity of residual cortical tissue has been identified as an important mediator of functional post-stroke recovery. Many studies have been directed toward describing biochemical, electrophysiological, and cytoarchitectural changes in residual cortex and correlating them with functional changes. Additionally, after neonatal stroke the thickness of residual tissue can change, the tissue can move, and tissue can fill in the stroke core. The purpose of the present study was to systematically investigate and document possible gross morphological changes in peri-infarct tissue after forelimb motor cortex stroke in the adult rat. Rats received a unilateral forelimb motor cortex stroke of equivalent size by pial strip devascularization or photothrombotic occlusion and were then examined using histology or magnetic resonance imaging (MRI) at 1 h, 1, 3, 7, 14, or 31 days post-stroke. Middle cerebral artery occlusion was used as a control stroke procedure. Decreases in cortical thickness, volume, and neural density were found to extend far beyond the stroke infarct and included most of the sensorimotor regions of the stroke and intact hemispheres. Movement of residual tissue towards the infarct was observed and confirmed using anatomical markers placed in intact cortical tissue at the time of stroke induction. The results are discussed in relation to the idea that extensive time-dependent morphological changes that occur in residual tissue must be considered when evaluating plasticity-related cortical changes associated with post-stroke recovery of function.

Compensation aids skilled reaching in aging and in recovery from forelimb motor cortex stroke in the rat.

Compensatory movements mediate success in skilled reaching for food after stroke to the forelimb region of motor cortex (MtCx) in the rat. The present study asks whether the neural plasticity that enables compensation after motor stroke is preserved in aging. In order to avoid potential confounding effects of age-related negative-learning, rats were trained in a single pellet reaching task during young-adulthood. Subgroups were retested before and after contralateral forelimb MtCx stroke via pial stripping given at 3, 18, or 23 months of age. Over a two-month post-stroke rehabilitation period, end point measures were made of learned nonuse, recovery, retention, and performance ratings were made of reaching movement elements. Prior to stroke, young and aged rats maintained equivalent end point performance but older rats displayed compensatory changes in limb use as measured with ratings of the elements of forelimb movement. Following stroke, the aged groups of rats were more impaired on end point, movement, and anatomical measures. Nevertheless, the aged rats displayed substantial recovery via the use of compensatory movements. Thus, this study demonstrates that the neural plasticity that mediates compensatory movements after stroke in young adults is preserved prior to and following stroke in aging.

Acute but not chronic differences in skilled reaching for food following motor cortex devascularization vs. photothrombotic stroke in the rat.

The variability in the behavioral outcome of human and nonhuman animals after stroke raises the question whether the way that a stroke occurs is a contributing factor. Photothrombotic stroke in rats has been reported to produce especially variable results, with some animals showing either slight to no impairment to other animals displaying severe impairments. The present study investigated this variability. Rats received three different-sized photothrombotic treatments and were contrasted to rats receiving a "standard" motor cortex stroke produced by pial stripping. Rats were assessed acutely and chronically on a skilled reaching for food task using end-point measures and movement assessment in a constraint-induced rehabilitation paradigm. The results indicated that as the size of the photothrombotic infarct approached the size of the pial strip infarct so did chronic behavioral deficits. Nevertheless there were differences in the time course of recovery. Rats with photothrombotic lesions of all sizes were less impaired in the acute period of recovery both on measures of learned nonuse and constrained-induced recovery. The findings are discussed in relation to the idea that whereas the course of recovery might be altered as a function of the type of stroke, chronic deficits are more closely related to the ensuing damage.

[Concerning a conflict nature of the "spatial delayed response" test]. / O konfliktnoi prirode testa "prostranstvennaia otsrochennaia reaktsiia".

Neuropsychological analysis of rats' performance of the spatial delayed response (SDR) in different testing conditions revealed a conflict nature of the indirect variation of the SDR task. It was found that the execution of the response based on the image short-term memory interferes with the response differentiation acquired during learning the rule of indirect SDR performance, i.e., during acquisition of the spatial discrimination. It is evident that the maximization of conditions, which promote the acquisition of response differentiation (additional training of animals for spatial discrimination), makes it difficult to perform the indirect variation of the SDR task, while the minimization of these conditions facilitates the correct task performance.