Inflammogenesis of Secondary Spinal Cord Injury

Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine.Grant #NPRP 4-571-3-171 from the Qatar National Research Fund(a member of Qatar Foundation)

Metabolic and Behavioral Compensatory Responses to Exercise Interventions: Barriers to Weight Loss

An activity-induced increase in energy expenditure theoretically disturbs energy balance (EB) by creating an acute energy deficit. Compensatory responses could influence the weight loss associated with the energy deficit. Individual variability in compensation for perturbations in EB could partly explain why some individuals fail to lose weight with exercise. It is accepted that the regulatory system will readily defend impositions that promote a negative EB. Therefore, a criticism of exercise interventions is that they will be ineffective and futile methods of weight control because the acute energy deficit is counteracted. Compensation for exercise-induced energy deficits can be categorized into behavioral or metabolic responses and automatic or volitional. An automatic compensatory response is a biological inevitability and considered to be obligatory. An automatic compensatory response is typically a metabolic consequence (e.g., reduced resting metabolic rate) of a negative EB. In contrast, a volitional compensatory response tends to be deliberate and behavioral, which the individual intentionally performs (e.g., increased snack intake). The purpose of this review is to highlight the various metabolic and behavioral compensatory responses that could reduce the effectiveness of exercise and explain why some individuals experience a lower than expected weight loss. We propose that the extent and degree of compensation will vary between individuals. That is, some individuals will be predisposed to compensatory responses that render them resistant to the weight loss benefits theoretically associated with an exercise-induced increase in energy expenditure. Therefore, given the inter-individual variability in behavioral and metabolic compensatory responses, exercise prescriptions might be more effective if tailored to suit individuals