Segmental arterial mediolysis: a commonly overlooked aetiology of acute abdominal pain.

Segmental arterial mediolysis (SAM) is an uncommon condition and commonly missed diagnostic aetiology of acute abdominal pain, initially described in 1976. SAM is a non-inflammatory, non-atherosclerotic vasculopathy mostly involving the abdominal arteries with notable asymmetric involvement of the walls of the mesenteric arteries and their branches. Clinical presentation ranges from postprandial abdominal discomfort suggestive of mesenteric ischaemia to intra-abdominal bleeding. Pathophysiological explanation and prognosis of these cases are not well understood and therefore no clear guidelines for management exist. In this case report, we emphasise the imaging modalities used to reach the diagnosis and the management options available.

Disease progression in a mouse model of amyotrophic lateral sclerosis: the influence of chronic stress and corticosterone.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron cell loss, muscular atrophy, and a shortened life span. Survival is highly variable, as some patients die within months, while others live for many years. Exposure to stress or the development of a nonoptimal stress response to disease might account for some of this variability. We show in the SOD1(G93A) mouse model of ALS that recurrent exposure to restraint stress led to an earlier onset of astrogliosis and microglial activation within the spinal cord, accelerated muscular weakness, and a significant decrease in median survival (105 vs. 122 d) when compared to nonstressed animals. Moreover, during normal disease course, ALS mice display a cacostatic stress response by developing an aberrant serum corticosterone circadian rhythm. Interestingly, we also found that higher corticosterone levels were significantly correlated with both an earlier onset of paralysis (males: r(2)=0.746; females: r(2)=0.707) and shorter survival times (males: r(2)=0.680; females: r(2)=0.552) in ALS mice. These results suggest that stress is capable of accelerating disease progression and that strategies that modulate glucocorticoid metabolism might be a viable treatment approach for ALS.

Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders.

Adeno-associated virus type 9 (AAV9) is a powerful tool for delivering genes throughout the central nervous system (CNS) following intravenous injection. Preclinical results in pediatric models of spinal muscular atrophy (SMA) and lysosomal storage disorders provide a compelling case for advancing AAV9 to the clinic. An important translational step is to demonstrate efficient CNS targeting in large animals at various ages. In the present study, we tested systemically injected AAV9 in cynomolgus macaques, administered at birth through 3 years of age for targeting CNS and peripheral tissues. We show that AAV9 was efficient at crossing the blood-brain barrier (BBB) at all time points investigated. Transgene expression was detected primarily in glial cells throughout the brain, dorsal root ganglia neurons and motor neurons within the spinal cord, providing confidence for translation to SMA patients. Systemic injection also efficiently targeted skeletal muscle and peripheral organs. To specifically target the CNS, we explored AAV9 delivery to cerebrospinal fluid (CSF). CSF injection efficiently targeted motor neurons, and restricted gene expression to the CNS, providing an alternate delivery route and potentially lower manufacturing requirements for older, larger patients. Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations.

Physical activity and neuroprotection in amyotrophic lateral sclerosis.

Physical exercise exerts a wide range of benefits on an organism's overall health and well-being. Exercise contributes positively toward an individual's healthy weight, muscle strength, immune system, and cardiovascular health. Indeed, exercise has been demonstrated to reduce life-threatening conditions such as high blood pressure, heart disease, obesity, and diabetes. Of particular interest to this review, exercise has also been shown to be neuroprotective in both the central and peripheral nervous systems. Naturally, such findings apply broadly to the study of neurodegenerative disease with numerous reports demonstrating that exercise has beneficial effects on disease progression. One of the most devastating neurodegenerative diseases is amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease in the United States, or motor neuron disease in the United Kingdom, resulting from the progressive loss of brain and spinal cord motor neurons. Several human studies show that moderate exercise regimens improve ALS patients' scoring on functionality tests and ameliorate disease symptoms. Other promising recent works using transgenic mouse models of familial ALS have shown markedly slowed disease progression, improved function, and extension of survival in moderately exercised animals. Possible explanations for these findings include the exercise-induced changes in motor neuron morphology, muscle-nerve interaction, glial activation, and altering levels of gene expression of anti-apoptotic proteins and neurotrophic factors in the active tissue. Here we review the current literature on exercise and motor neuron disease, focusing on rodent and human studies to define the proper type, intensity, and duration of exercise necessary to enhance neuron survival as well discuss current mechanistic studies to further define the exercise-mediated pathways of neuroprotection.