After cerebral ischemia, events like neural plasticity and tissue reorganization intervene in lesioned and non-lesioned areas of the brain. These processes are tightly related to functional improvement and successful rehabilitation in patients. Plastic remodeling in the brain is associated with limited spontaneous functional recovery in patients. Improvement depends on the initial deficit, size, nature and localization of the infarction, together with the sex and age of the patient, all of them affecting the favorable outcome of reorganization and repair of damaged areas. A better understanding of cerebral plasticity is pivotal to design effective therapeutic strategies. Experimental models and clinical studies have fueled the current understanding of the cellular and molecular processes responsible for plastic remodeling. In this review, we describe the known mechanisms, in patients and animal models, underlying cerebral reorganization and contributing to functional recovery after ischemic stroke. We also discuss the manipulations and therapies that can stimulate neural plasticity. We finally explore a new topic in the field of ischemic stroke pathophysiology, namely the brain-gut axis.

Tissue regeneration is a rapidly evolving and interdisciplinary field at the intersection of life science, biology, material science, and engineering. Centrally, it involves functional cell-free or cell-laden constructs or biomaterial scaffolds that are fabricated utilizing various strategies. [1] Cell-free biomaterial scaffolds implanted directly at the sites of injury may mechanically support local cells to promote local tissue repair. [2] Furthermore, they can be functionalized both on the surface or in the interior with bioactive materials to stimulate regeneration of functional tissues. [3] In cell therapy applications, cell-laden constructs may enhance both survival and differentiation of the therapeutic cells compared with cell transplantation alone. The grafted cells may then ideally replace lost tissue and/or exert beneficial effects on the host tissue. [4] Among different biomaterial constructs, 3D fibrous scaffolds recreate a 3D microenvironment, which closely resembles the native extracellular matrix (ECM), including both structural and biochemical properties that guide cell survival and differentiation. [5] Scaffolds with fibrous networks possess unique characteristics, including sufficiently high interconnected porosity, high specific surface area, tunable mechanical properties, as well as optimal morphological features. The high porosity of the fibrous scaffolds facilitates mass transfer for effective nutrient supply, oxygen diffusion, metabolic waste removal, and enhancement of intercellular communications, consequently allowing high cell viability and function throughout the entire scaffold. [6] In addition, compared with 2D culture, the 3D cell culture provides a more realistic biochemical and biomechanical microenvironment, [7] creating an optimal environment for cell migration, proliferation, and differentiation. Hence, nanofibrous scaffolds with appropriate biomechanical properties are highly suitable for tissue engineering. [8] Electrospinning, as a relatively simple and versatile fiber preparation technique, has been developed to create fiber-based constructs in combination with cells, bioactive molecules, proteins, and biocompatible nanomaterials. [9] Many studies have demonstrated that the electrospinning technology has the potential for significant progress within the field of tissue regeneration. Chen et al. [10] summarized the methods for producing electrospun 1D nanofiber bundles, 2D

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Background: Stroke is the first cause of disability in adults in western countries. Infarct of the internal capsule (IC) may be related to motor impairment and poor prognosis in stroke patients. Functional deficits due to medium-sized infarcts are difficult to predict, except if the specific site of the lesion is taken into account. None of the few pre-clinical models recapitulating this type of stroke has shown clear, reproducible, and long-lasting sensorimotor deficits. Here, we developed a rat model of lacunar infarction within the IC, key structure of the sensorimotor pathways, by precise injection of malonate.Methods: The mitochondrial toxin malonate was injected during stereotactic surgery into the IC of rat brains. Rats were divided in three groups: two groups received malonate solution at 1.5M (n = 12) or at 3M (n = 10) and a sham group (n = 5) received PBS. Three key motor functions usually evaluated following cerebral lesion in the clinic strength, target reaching, and fine dexterity were assessed in rats by a forelimb grip strength test, a skilled reaching task (staircase) for reaching and dexterity, and single pellet retrieval task. Sensorimotor functions were evaluated by a neurological scale. Live brain imaging, using magnetic resonance (MRI), and post-mortem immunohistochemistry in brain slices were performed to characterize the lesion site after malonate injection.Results: Intracerebral injection of malonate produced a 100% success rate in inducing a lesion in the IC. All rats receiving the toxin, regardless the dose injected, had similar deficits in strength and dexterity of the contralateral forepaw, and showed significant neurological impairment. Additionally, only partial recovery was observed with respect to strength, while no recovery was observed for dexterity and neurological deficit. MRI and immunostaining show volume size and precise location of the lesion in the IC, destruction of axonal structures and Wallerian degeneration of fibers in the area above the injection site.Conclusions: This pre-clinical model of lacunar stroke induces a lesion in the IC with measurable and reproducible sensorimotor deficits, and limited recovery with stabilization of performance 2 weeks post-injury. Future therapies in stroke may be successfully tested in this model.