Oxygen treatment reduces neurological deficits and demyelination in two animal models of multiple sclerosis.

Aims: The objective of the study is to explore the importance of tissue hypoxia in causing neurological deficits and demyelination in the inflamed CNS, and the value of inspiratory oxygen treatment, using both active and passive experimental autoimmune encephalomyelitis (EAE).

Methods: Normobaric oxygen treatment was administered to Dark Agouti rats with either active or passive EAE, compared with room air-treated, and naïve, controls.

Results: Severe neurological deficits in active EAE were significantly improved after just 1 h of breathing approximately 95% oxygen.

Nimodipine Reduces Dysfunction and Demyelination in Models of Multiple Sclerosis.

Objective: Treatment of relapses in multiple sclerosis (MS) has not advanced beyond steroid use, which reduces acute loss of function, but has little effect on residual disability. Acute loss of function in an MS model (experimental autoimmune encephalomyelitis [EAE]) is partly due to central nervous system (CNS) hypoxia, and function can promptly improve upon breathing oxygen. Here, we investigate the cause of the hypoxia and whether it is due to a deficit in oxygen supply arising from impaired vascular perfusion.

Hyperspectral Imaging of the Hemodynamic and Metabolic States of the Exposed Cortex: Investigating a Commercial Snapshot Solution.

Hyperspectral imaging (HSI) systems have the potential to retrieve in vivo hemodynamic and metabolic signals from the exposed cerebral cortex. The use of multiple narrow wavelength bands in the near infrared (NIR) range theoretically allows not only to image brain tissue oxygenation and hemodynamics via mapping of hemoglobin concentration changes, but also to directly quantify cerebral metabolism via measurement of the redox states of mitochondrial cytochrome-c-oxidase (CCO). The aim of this study is to assess the possibility of performing hyperspectral imaging of in vivo cerebral oxyhemoglobin (HbO), deoxyhemoglobin (HHb) and oxidized CCO (oxCCO) using commercially available HSI devices.

A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature.

Quantification of blood oxygen saturation (SO) in vivo is essential for understanding the pathogenesis of diseases in which hypoxia is thought to play a role, including inflammatory disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). We describe a low-cost multispectral microscope and oximetry technique for calibration-free absolute oximetry of surgically exposed blood vessels in vivo. We imaged the vasculature of the dorsal spinal cord in healthy rats, and varied inspired oxygen (FiO) in order to evaluate the sensitivity of the imaging system to changes in SO.

Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis.

Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.

Cause and prevention of demyelination in a model multiple sclerosis lesion.

Objective: Demyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination can occur in the relative absence of lymphocytes, and with distinctive characteristics suggestive of a tissue energy deficit. The objective was to examine an experimental model of the early multiple sclerosis lesion and identify pathogenic mechanisms and opportunities for therapy.

Neurological deficits caused by tissue hypoxia in neuroinflammatory disease.

Objective: To explore the presence and consequences of tissue hypoxia in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).

Methods: EAE was induced in Dark Agouti rats by immunization with recombinant myelin oligodendrocyte glycoprotein and adjuvant. Tissue hypoxia was assessed in vivo using 2 independent methods: an immunohistochemical probe administered intravenously, and insertion of a physical, oxygen-sensitive probe into the spinal cord.

Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury.

Objective: To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects.

Design: Cross-sectional study.

Setting: Clinical research unit.

Recombinant human TNFalpha induces concentration-dependent and reversible alterations in the electrophysiological properties of axons in mammalian spinal cord.

Increased expression of the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) and its soluble receptors is evident within the central nervous system (CNS) following traumatic brain injury and spinal cord injury. TNFalpha is integral to the acute inflammatory cascade that follows neurotrauma and has been shown to have both beneficial and detrimental properties. We examined the effects of varying concentrations (1-5000 ng/mL) of recombinant human TNFalpha (rhTNFalpha) on select electrophysiological properties of excised guinea pig spinal cord tissue.