International e-Delphi survey to define best practice in the reporting of intracranial pressure monitoring recording data.

Introduction: Intracranial pressure (ICP) monitoring is a very commonly performed neurosurgical procedure but there is a wide variation in how it is reported, hindering analysis of it. The current study sought to generate consensus on the reporting of ICP monitoring recording data.

Research Question: "What should be included in an ICP monitoring report?"

Material And Methods: The exercise was completed via a modified eDelphi survey.

Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury.

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture risk. Prevention and treatment of osteoporotic fractures is essential for reductions in mortality, morbidity, and the economic burden, particularly considering the aging global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralyzed limbs following complete spinal cord injury (SCI).

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling.

Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here, we investigate the role of interneurons that continue to express NPY (NPY-INs) in the adult mouse spinal cord.

Spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury in skeletally mature rats.

Objective: Characterise the spatiotemporal responses of trabecular and cortical bone to complete spinal cord injury (SCI) in the skeletally mature rat in the acute (4-week) period following injury.

Methods: The spinal cord of 5-month old male rats was transected at the T9 level. Outcome measures were assessed using micro-computed tomography, three-point bending and serum markers at 1-, 2-, and 4-weeks post-transection.

A novel poly-ε-lysine based implant, Proliferate®, for promotion of CNS repair following spinal cord injury.

The limited regenerative capacity of the CNS poses formidable challenges to the repair of spinal cord injury (SCI). Two key barriers to repair are (i) the physical gap left by the injury, and (ii) the inhibitory milieu surrounding the injury, the glial scar. Biomaterial implantation into the injury site can fill the cavity, provide a substrate for cell migration, and potentially attenuate the glial scar.

Global and site-specific analysis of bone in a rat model of spinal cord injury-induced osteoporosis.

Micro-Computed Tomography bone analysis is the gold standard method for assessing trabecular and cortical bone microarchitecture in small animal bones. This technique reports morphometric parameters as averages over selected volumes of interest (VOIs). This study proposes the introduction of an additional global 2D morphometric step into the analysis process, that provides a survey of the underlying morphometric variation present throughout both trabecular and cortical bone.

Morphological and functional properties distinguish the substance P and gastrin-releasing peptide subsets of excitatory interneuron in the spinal cord dorsal horn.

Excitatory interneurons account for the majority of neurons in the superficial dorsal horn, but despite their presumed contribution to pain and itch, there is still limited information about their organisation and function. We recently identified 2 populations of excitatory interneuron defined by expression of gastrin-releasing peptide (GRP) or substance P (SP). Here, we demonstrate that these cells show major differences in their morphological, electrophysiological, and pharmacological properties.

Author Correction: Circuit dissection of the role of somatostatin in itch and pain.

In the version of this article initially published online, the labels were switched for the right-hand pair of bars in Fig. 4e. The left one of the two should be Chloroquine + veh, the right one Chloroquine + CNO.

Circuit dissection of the role of somatostatin in itch and pain.

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin.

Human olfactory mesenchymal stromal cell transplants promote remyelination and earlier improvement in gait co-ordination after spinal cord injury.

Autologous cell transplantation is a promising strategy for repair of the injured spinal cord. Here we have studied the repair potential of mesenchymal stromal cells isolated from the human olfactory mucosa after transplantation into a rodent model of incomplete spinal cord injury. Investigation of peripheral type remyelination at the injury site using immunocytochemistry for P0, showed a more extensive distribution in transplanted compared with control animals.

Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis.

A combined electrophysiological and morphological study of neuropeptide Y-expressing inhibitory interneurons in the spinal dorsal horn of the mouse.

The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population.

Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets.

The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter.

Gait analysis in a Mecp2 knockout mouse model of Rett syndrome reveals early-onset and progressive motor deficits.

Rett syndrome (RTT) is a genetic disorder characterized by a range of features including cognitive impairment, gait abnormalities and a reduction in purposeful hand skills. Mice harbouring knockout mutations in the Mecp2 gene display many RTT-like characteristics and are central to efforts to find novel therapies for the disorder. As hand stereotypies and gait abnormalities constitute major diagnostic criteria in RTT, it is clear that motor and gait-related phenotypes will be of importance in assessing preclinical therapeutic outcomes.

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn.

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons.

Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse.

Background: Inhibitory interneurons in the superficial dorsal horn play important roles in modulating sensory transmission, and these roles are thought to be performed by distinct functional populations. We have identified 4 non-overlapping classes among the inhibitory interneurons in the rat, defined by the presence of galanin, neuropeptide Y, neuronal nitric oxide synthase (nNOS) and parvalbumin. The somatostatin receptor sst2A is expressed by ~50% of the inhibitory interneurons in this region, and is particularly associated with nNOS- and galanin-expressing cells.

A comparative study of glial and non-neural cell properties for transplant-mediated repair of the injured spinal cord.

Cell transplantation is one strategy for encouraging regeneration after spinal cord injury and a range of cell types have been investigated for their repair potential. However, variations in study design complicate determination of which cells are most effective. In this study we have carried out a direct comparison of the regenerative and integrative properties of several cell preparations following transplantation into the lesioned rat spinal cord.

Transplant-mediated repair properties of rat olfactory mucosal OM-I and OM-II sphere-forming cells.

Olfactory mucosa is a source of cells for transplant-mediated repair of spinal cord injury (SCI) and is currently being assessed in clinical trials. We previously reported that olfactory mucosa can generate two types of sphere-forming cells with stem cell-like properties. Here we have assessed the repair potential of these cells in a rodent SCI model.

Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach.

Lamina II contains a large number of interneurons involved in modulation and transmission of somatosensory (including nociceptive) information. However, its neuronal circuitry is poorly understood due to the difficulty of identifying functional populations of interneurons. This information is important for understanding nociceptive processing and for identifying changes that underlie chronic pain.

Evidence against AMPA receptor-lacking glutamatergic synapses in the superficial dorsal horn of the rat spinal cord.

Pure NMDA receptor (NMDAr)-mediated EPSCs, thought to correspond to "silent" glutamatergic synapses that lack AMPA receptors (AMPArs), have been observed in superficial spinal dorsal horn of neonatal but not adult rats. Recent anatomical studies suggest that AMPArs are present at virtually all glutamatergic synapses in this region in adults. We used antigen retrieval to examine colocalization of AMPArs and PSD-95 (a marker for glutamatergic synapses) in laminae I-II of neonatal and adult rats.

Olfactory mucosa for transplant-mediated repair: a complex tissue for a complex injury?

Damage to the brain and spinal cord leads to permanent functional disability because of the very limited capacity of the central nervous system (CNS) for repair. Transplantation of cells into regions of CNS damage represents one approach to enhancing this repair. At present, the ideal cell type for transplant-mediated repair has not been identified but autologous transplantation would be advantageous.

Identification of nonepithelial multipotent cells in the embryonic olfactory mucosa.

Olfactory mucosal (OM) tissue, a potential source of stem cells, is currently being assessed in the clinic as a candidate tissue for transplant-mediated repair of spinal cord injury. We examined the ability of embryonic rat OM tissue to generate stem cells using culture conditions known to promote neural stem cell proliferation. Primary spheres formed that proliferated and exhibited two main morphologies: (a) CNS neurosphere-like (OM-I) and (b) small, tight spheroid-like (OM-II).

FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis.

After injury, the CNS undergoes an astrocyte stress response characterized by reactive astrocytosis/proliferation, boundary formation, and increased glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycan (CSPG) expression. Previously, we showed that in vitro astrocytes exhibit this stress response when in contact with Schwann cells but not olfactory ensheathing cells (OECs). In this study, we confirm this finding in vivo by demonstrating that astrocytes mingle with OECs but not Schwann cells after injection into normal spinal cord.