Neuronano (Sweden)

Abstract A paradigm in neurology is that brain injury-induced motor deficits (e.g. hemiparesis and hemiplegia) arise due to aberrant activity of descending neural pathways. We discovered that a unilateral injury of the hindlimb sensorimotor cortex of rats with completely transected thoracic spinal cord produces hindlimb postural asymmetry with contralateral flexion, and asymmetric changes in nociceptive hindlimb withdrawal reflexes and gene expression patterns in lumbar spinal cord. The injury-induced postural effects were abolished by prior hypophysectomy and were mimicked by transfusion of serum from animals with unilateral brain injury. Antagonists of the opioid and vasopressin receptors blocked formation of hindlimb postural asymmetry suggesting that these neurohormones mediate effects of brain injury on lateralized motor responses. Our data indicate that descending neural control of spinal circuits is complemented by a previously unknown humoral signaling from injured brain to the contra- and ipsilesional hindlimbs, and suggest the existence of a body side-specific neuroendocrine regulation in bilaterally symmetric animals.

Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the synthesis of serotonin, dopamine, and certain trace amines and is present in a variety of organs including the brain and spinal cord. It is previously reported that in mammalian spinal cord AADC cells (called D-cells) were largely confined to a region around the central canal and that they do not produce monoamines. To date, there has not been a detailed description of their distribution and morphology in mammals. In the present study this issue is systematically investigated using immunohistochemistry. We have found that AADC cells in the rat spinal cord are both more numerous and more widely distributed than previously reported. In the gray matter, AADC neurons immunolabeled for NeuN were not only found in the region around the central canal but also in the dorsal horn, intermediate zone, and ventral horn. In the white matter a large number of glial cells were AADC-immunopositive in different spinal segments and the vast majority of these cells expressed oligodendrocyte and radial glial phenotypes. Additionally, a small number of AADC neurons labeled for NeuN were found in the white matter along the ventral median fissure. The shapes and sizes of AADC neurons varied according to their location. For example, throughout cervical and lumbar segments AADC neurons in the intermediate zone and ventral horn tended to be rather large and weakly immunolabeled, whereas those in comparable regions of sacrocaudal segments were smaller and more densely immunolabeled. The diverse morphological characteristics of the AADC cells suggests that they could be further divided into several subtypes. These results indicate that AADC cells are heterogeneously distributed in the rat spinal cord and they may exert different functions in different physiological and pathological situations.

BackgroundLittle is known about factors contributing to the altered movement patterns observed in many individuals with anterior cruciate ligament (ACL) injury. We addressed whether altered muscular activity is such a factor.Methods16 participants with unilateral, non-reconstructed ACL rupture were scored for altered movement patterns according to Test for Substitution Patterns (TSP), which includes the single-leg squat (SLS). Surface electromyography (SEMG), was recorded in the lower extremities at initiation of weight-transfer from double-leg to single-leg stance (eyes closed), simulating the initiation of an SLS. Normalised SEMG amplitudes 200–300 ms after weight-transfer initiation were compared between injured and non-injured sides, and correlated to the TSP scores for the SLS. Peak absolute SEMG amplitudes during 5 TSP test movements were also compared between sides.ResultsAt weight-transfer initiation, muscle activity was lower in the tibialis anterior, gastrocnemius and peroneus longus muscles on the injured side. Low muscle activity correlated moderately to worse TSP scores for the SLS for the gluteus medius (rs=−0.56, p=0.03), and gastrocnemius muscles (rs=−0.56, p=0.02). Median peak absolute amplitude during TSP movements was lower in the quadriceps, gastrocnemius and peroneus longus muscles on the injured side.ConclusionsThe altered patterns of muscle activity at weight-transfer initiation, correlations between lower activity at movement initiation and altered movement patterns during SLS and the altered peak amplitudes during TSP movements together indicate alterations in sensorimotor control that may contribute to the observed altered movement patterns. Future studies will determine if exercises targeting muscle activity initiation should complement customary ACL injury rehabilitation.

Summary: Brain Computer interfaces (BCIs) are stable inside the brain over long periods of time and that have minimal effects on the physiological conditions of the neural tissue. This chapter reviews the state-of-the-art of neural interfaces and the concepts behind recent research and development of biocompatible BCIs. It focuses on various tissue responses in the brain to an implanted foreign body. A number of implantable micro-electrode arrays have been developed for use as neural interfaces for BCIs. The chapter then focuses on how to minimize the foreign body reactions and loss of neurons around the implant that has resulted in identification of several key features that electrodes need to fulfill and the development of novel ultra-thin/elastic and flexible constructs that fulfill these requirements. By using hard but dissolvable matrix materials, arrays of ultra-flexible electrodes can be implanted. Importantly, gelatin-based embedding materials also appear to protect the neurons close to the BCI. (Less)

Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca2+ ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS.

Background: A major challenge in the field of neural interfaces is to overcome the problem of poor stability of neuronal recordings, which impedes long-term studies of individual neurons in the brain. Conceivably, unstable recordings reflect relative movements between electrode and tissue. To address this challenge, we have developed a new ultra-flexible electrode array and evaluated its performance in awake non-restrained animals.Methods:An array of eight separated gold leads (4 × 10 μm), individually flexible in 3D, were cut from a gold sheet using laser milling and insulated with Parylene C. To provide structural support during implantation into rat cortex, the electrode array was embedded in a hard gelatin based material, which dissolves after implantation. Recordings were made during 3 weeks. At termination, the animals were perfused with fixative and frozen to prevent dislocation of the implanted electrodes. A thick slice of brain tissue, with the electrode array still in situ, was made transparent using methyl salicylate to evaluate the conformation of the implanted electrode array.Results: Median noise levels and signal/noise remained relatively stable during the 3 week observation period; 4.3–5.9 μV and 2.8–4.2, respectively. The spike amplitudes were often quite stable within recording sessions and for 15% of recordings where single-units were identified, the highest-SNR unit had an amplitude higher than 150 μV. In addition, high correlations (>0.96) between unit waveforms recorded at different time points were obtained for 58% of the electrode sites. The structure of the electrode array was well preserved 3 weeks after implantation.Conclusions: A new implantable multichannel neural interface, comprising electrodes individually flexible in 3D that retain its architecture and functionality after implantation has been developed. Since the new neural interface design is adaptable, it offers a versatile tool to explore the function of various brain structures.

Neural cultures are very useful in neuroscience, providing simpler and better controlled systems than the in vivo situation. Neural tissue contains two main cell types, neurons and glia, and interactions between these are essential for appropriate neuronal development. In neural cultures, glial cells tend to overgrow neurons, limiting the access to neuronal interrogation. There is therefore a pressing need for improved systems that enable a good separation when coculturing neurons and glial cells simultaneously, allowing one to address the neurons unequivocally. Here, we used substrates consisting of dense arrays of vertical nanowires intercalated by flat regions to separate retinal neurons and glial cells in distinct, but neighboring, compartments. We also generated a nanowire patterning capable of guiding optic nerve axons. The results will facilitate the design of surfaces aimed at studying and controlling neuronal networks.