In vivo biocompatibility assessment of 3D printed bioresorbable polymers for brain tissue regeneration. A feasibility study.

Introduction: The limited capacity of brain tissue to regenerate after acute injury, hampered by cell death, edema and inflammation, has led to an interest in promising and innovative approaches such as implantable regenerative scaffolds designed to improve brain plasticity. Leveraging the capabilities of bioprinting, these scaffolds can be tailored to match the intricate architecture of the brain.

Methods: In this methodological study, we performed in vivo biocompatibility assessments after a brain lesion on three distinct bioeliminable or bioresorbable materials: Poly(ethylene glycol) diacrylate (PEGDA), Polycaprolactone (PCL) and a PEGDA mixed with gelatin methacrylate (PEGDA-GelMA).

Evidence of cerebral hypoperfusion consecutive to ultrasound-mediated blood-brain barrier opening in rats.

Purpose: This work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats.

Methods: Two groups of n = 5 rats were included in this study. The first group was used to investigate the impact of BBB opening on the Arterial Spin Labeling (ASL) signal, in particular on the arterial transit time (ATT).

Long-Term Intranasal Nerve Growth Factor Treatment Favors Neuron Formation in Brain Tissue.

Objective: To date, no safe and effective pharmacological treatment has been clinically validated for improving post-stroke neurogenesis. Growth factors are good candidates but low safety has limited their application in the clinic. An additional restraint is the delivery route.

Present and future avenues of cell-based therapy for brain injury: The enteric nervous system as a potential cell source.

Cell therapy is a promising strategy in the field of regenerative medicine; however, several concerns limit the effective clinical use, namely a valid cell source. The gastrointestinal tract, which contains a highly organized network of nerves called the enteric nervous system (ENS), is a valuable reservoir of nerve cells. Together with neurons and neuronal precursor cells, it contains glial cells with a well described neurotrophic potential and a newly identified neurogenic one.

Controlling for lesions, kinematics and physiological noise: impact on fMRI results of spastic post-stroke patients.

Functional magnetic resonance imaging (fMRI) is a widely used technique for assessing brain function in both healthy and pathological populations. Some factors, such as motion, physiological noise and lesion presence, can contribute to signal change and confound the fMRI data, but fMRI data processing techniques have been developed to correct for these confounding effects. Fifteen spastic subacute stroke patients underwent fMRI while performing a highly controlled task (i.

Cross-Modal Functional Connectivity of the Premotor Cortex Reflects Residual Motor Output After Stroke.

Stroke is known to cause widespread activation and connectivity changes resulting in different levels of functional impairment. Recovery of motor functions is thought to rely mainly on reorganizations within the sensorimotor cortex, but increasing attention is being paid to other cerebral regions. To investigate the motor task-related functional connectivity (FC) of the ipsilesional premotor cortex (PMC) and its relation to residual motor output after stroke in a population of mostly poorly recoverd patients.

A Reproducible New Model of Focal Ischemic Injury in the Marmoset Monkey: MRI and Behavioural Follow-Up.

Ischemic stroke mostly affects the primary motor cortex and descending motor fibres, with consequent motor impairment. Pre-clinical models of stroke with reproducible and long-lasting sensorimotor deficits in higher-order animals are lacking. We describe a new method to induce focal brain damage targeting the motor cortex to study damage to the descending motor tracts in the non-human primate.

Post-stroke remodeling processes in animal models and humans.

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.

Interfacing cells with microengineered scaffolds for neural tissue reconstruction.

The development of cellular microenvironments suitable for neural tissue engineering purposes involves a plethora of research fields ranging from cell biology to biochemistry, neurosciences, physics, nanotechnology, mechanobiology. In the last two decades, this multi-disciplinary activity has led to the emergence of numerous strategies to create architectures capable of reproducing the topological, biochemical and mechanical properties of the extracellular matrix present in the central (CNS) and peripheral nervous system (PNS). Some of these approaches have succeeded in inducing the functional recovery of damaged areas in the CNS and the PNS to address the current lack of effective medical treatments for this type of injury.

Wet spinning and radial self-assembly of a carbohydrate low molecular weight gelator into well organized hydrogel filaments.

In this work, we describe how a simple single low molecular weight gelator (LMWG) molecule - N-heptyl-d-galactonamide, which is easy to produce at the gram scale - is spun into gel filaments by a wet spinning process based on solvent exchange. A solution of the gelator in DMSO is injected into water and the solvent diffusion triggers the supramolecular self-assembly of the N-heptyl-d-galactonamide molecules into nanometric fibers. These fibers entrap around 97% of water, thus forming a highly hydrated hydrogel filament, deposited in a well organized coil and locally aligned.

Focal Malonate Injection Into the Internal Capsule of Rats as a Model of Lacunar Stroke.

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.

Serotonin Selective Reuptake Inhibitors (SSRIs) and Stroke.

Purpose Of Review: The interest in SSRIs after stroke has increased in the past few years, with better knowledge of post-stroke depression and with the demonstrated capacity of some SSRIs to act on the functional recovery of non-depressed subjects.

Recent Findings: Arguments for the action of SSRIs in favour of post-stroke neurological function recovery have improved through new elements: basic science and preclinical data, positive clinical trials and repeated series of stroke patient meta-analysis, and confirmation of favourable safety conditions in post-stroke patients. Global coherence is appearing, showing that SSRIs improve stroke recovery in non-depressed patients when given for 3 months after the stroke, with highly favourable safety conditions and a favourable benefit/risk ratio.

Simple Synthetic Molecular Hydrogels from Self-Assembling Alkylgalactonamides as Scaffold for 3D Neuronal Cell Growth.

In this work, we demonstrated that the hydrogel obtained from a very simple and single synthetic molecule, N-heptyl-galactonamide was a suitable scaffold for the growth of neuronal cells in 3D. We evidenced by confocal microscopy the presence of the cells into the gel up to a depth of around 200 μm, demonstrating that the latter was permissive to cell growth and enabled a true 3D colonization and organization. It also supported successfully the differentiation of adult human neuronal stem cells (hNSCs) into both glial and neuronal cells and the development of a really dense neurofilament network.

Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants.

Stroke represents the first cause of adult acquired disability. Spontaneous recovery, dependent on endogenous neurogenesis, allows for limited recovery in 50% of patients who remain functionally dependent despite physiotherapy. Here, we propose a review of novel drug therapies with strong potential in the clinic.

Five-day course of paired associative stimulation fails to improve motor function in stroke patients.

Background: Non-invasive brain stimulation has been studied as a therapeutic adjunct for upper-limb recovery in patients with stroke. One type of stimulation, paired associative stimulation (PAS), has effects on plasticity in both patients and healthy participants. Lasting several hours, these effects are reversible and topographically specific.

Action, observation or imitation of virtual hand movement affect differently regions of the mirror neuron system and the default mode network.

Virtual reality (VR)-based paradigms use visual stimuli that can modulate visuo-motor networks leading to the stimulation of brain circuits. The aims of this study were to compare the changes in blood-oxygenation level dependent (BOLD) signal when watching and imitating moving real (RH) and virtual hands (VH) in 11 healthy participants (HP). No differences were found between the observation of RH or VH making this VR-based experiment a promising tool for rehabilitation protocols.

Regenerative potential of primary adult human neural stem cells on micropatterned bio-implants boosts motor recovery.

Background: The adult brain is unable to regenerate itself sufficiently after large injuries. Therefore, hopes rely on therapies using neural stem cell or biomaterial transplantation to sustain brain reconstruction. The aim of the present study was to evaluate the improvement in sensorimotor recovery brought about by human primary adult neural stem cells (hNSCs) in combination with bio-implants.

Cerebral imaging of post-stroke plasticity and tissue repair.

Six months after stroke onset, 50 % of patients are still disabled and dependent, while many brain mechanisms of recovery remain partially unknown or misunderstood. However, brain imaging and cerebral connectivity analytical techniques have provided invaluable insights into such mechanisms and identified two main patterns of brain reorganization depending on stroke severity. The contralesional primary motor cortex can take over motor function in severely impaired patients, whereas the ipsilesional motor cortex or hemisphere reorganize themselves in good recoverers.

Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

Introduction: Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression.

Methods: A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression.

A shear-induced network of aligned wormlike micelles in a sugar-based molecular gel. From gelation to biocompatibility assays.

A new low molecular weight hydrogelator with a saccharide (lactobionic) polar head linked by azide-alkyne click chemistry was prepared in three steps. It was obtained in high purity without chromatography, by phase separation and ultrafiltration of the aqueous gel. Gelation was not obtained reproducibly by conventional heating-cooling cycles and instead was obtained by shearing the aqueous solutions, from 2 wt% to 0.

Multiphoton Direct Laser Writing and 3D Imaging of Polymeric Freestanding Architectures for Cell Colonization.

The realization of 3D architectures for the study of cell growth, proliferation, and differentiation is a task of fundamental importance for both technological and biological communities involved in the development of biomimetic cell culture environments. Here we report the fabrication of 3D freestanding scaffolds, realized by multiphoton direct laser writing and seeded with neuroblastoma cells, and their multitechnique characterization using advanced 3D fluorescence imaging approaches. The high accuracy of the fabrication process (≈200 nm) allows a much finer control of the micro- and nanoscale features compared to other 3D printing technologies based on fused deposition modeling, inkjet printing, selective laser sintering, or polyjet technology.

Disruption of posteromedial large-scale neural communication predicts recovery from coma.

Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks.

Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation.