Complement-dependent neuroinflammation in spinal cord injury: from pathology to therapeutic implications.

Spinal cord injury remains a major cause of disability in young adults, and beyond acute decompression and rehabilitation, there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population. Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation, a similar role for complement in spinal neuroinflammation is a focus of ongoing research. In this work, we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins, triggers of complement activation, and role of effector functions in the pathology.

Association of Cerebrovascular Injury and Secondary Vascular Insult With Poor Outcomes After Gunshot Wound to the Head in a Large Civilian Population.

Background And Objectives: Cerebrovascular injury (CVI) after civilian gunshot wound to the head (GSWH) likely contributes to poor outcomes, but little supporting evidence exists. The purpose of this study was to determine whether intracranial CVI from GSWH and secondary vascular insult (stroke or rehemorrhage) were associated with poor outcomes in a large civilian population.

Methods: This was a single-institution, retrospective cohort study on patients admitted between January 2014 and July 2022 at a large, metropolitan, level-1 trauma center.

The Role of Vitamin B in the Management and Optimization of Treatment in Patients With Degenerative Cervical Myelopathy.

Study Design: Narrative review.

Objectives: To discuss the relationship between degenerative cervical myelopathy (DCM) and vitamin B deficiency. Specifically, it is the aim to outline the rational for future research into assessment and therapeutic optimization of vitamin B in the treatment of DCM.

Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: A systematic review of cases.

Objective: Vitamin B12 deficiency can lead to subacute combined degeneration (SCD). Nitrous oxide (NO) is an anesthetic which oxidizes the cobalt ion of vitamin B12, interfering with its function as a coenzyme. In this study, we conduct a systematic review of reported cases of SCD following nitrous oxide anesthesia.

Degenerative Cervical Myelopathy: A Clinical Review.

Degenerative Cervical Myelopathy (DCM) is the most common form of spinal cord impairment in adults and results in disability and reduced quality of life. DCM can present with a wide set of clinical and imaging findings, including: 1) pain and reduced range of motion of the neck, and motor and sensory deficits on clinical exam, and 2) cord compression due to static and dynamic injury mechanisms resulting from degenerative changes of the bone, ligaments, and intervertebral discs on MRI. The incidence and prevalence of DCM has been estimated at a minimum of 4.

Genetic deletion and pharmacological inhibition of Nogo-66 receptor impairs cognitive outcome after traumatic brain injury in mice.

Functional recovery is markedly restricted following traumatic brain injury (TBI), partly due to myelin-associated inhibitors including Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), that all bind to the Nogo-66 receptor-1 (NgR1). In previous studies, pharmacological neutralization of both Nogo-A and MAG improved outcome following TBI in the rat, and neutralization of NgR1 improved outcome following spinal cord injury and stroke in rodent models. However, the behavioral and histological effects of NgR1 inhibition have not previously been evaluated in TBI.

Memory impairment in transgenic Alzheimer mice requires cellular prion protein.

Soluble oligomers of the amyloid-beta (Abeta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). Recently, we reported that synthetic Abeta oligomers bind to cellular prion protein (PrP(C)) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric Abeta peptide. We hypothesized that PrP(C) is essential for the ability of brain-derived Abeta to suppress cognitive function.

Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers.

A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-beta peptide of 40-42 amino acid residues. Prefibrillar, soluble oligomers of amyloid-beta have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction. At nanomolar concentrations, soluble amyloid-beta oligomers block hippocampal long-term potentiation, cause dendritic spine retraction from pyramidal cells and impair rodent spatial memory.

Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice.

The production and aggregation of cerebral amyloid-beta (Abeta) peptide are thought to play a causal role in Alzheimer's disease (AD). Previously, we found that the Nogo-66 receptor (NgR) interacts physically with both Abeta and the amyloid precursor protein (APP). The inverse correlation of Abeta levels with NgR levels within the brain may reflect regulation of Abeta production and/or Abeta clearance.

Alzheimer precursor protein interaction with the Nogo-66 receptor reduces amyloid-beta plaque deposition.

Pathophysiologic hypotheses for Alzheimer's disease (AD) are centered on the role of the amyloid plaque Abeta peptide and the mechanism of its derivation from the amyloid precursor protein (APP). As part of the disease process, an aberrant axonal sprouting response is known to occur near Abeta deposits. A Nogo to Nogo-66 receptor (NgR) pathway contributes to determining the ability of adult CNS axons to extend after traumatic injuries.