Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders. Here, we describe the current roles of sEH in the pathology and treatment of CNS disorders such as stroke, traumatic brain injury, Parkinson's disease, epilepsy, cognitive impairment, dementia and depression. In view of the robust anti-inflammatory effects of stem cells, we also outlined the potency of stem cell treatment and sEH inhibitors as a combination therapy for these CNS disorders. This review highlights the gaps in current knowledge about the pathologic and therapeutic roles of sEH in CNS disorders, which should guide future basic science research towards translational and clinical applications of sEH inhibitors for treatment of neurological diseases.
Sex differences have been well identified in many brain tumors. Even though glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has the worst outcome, well-established differences between men and women are limited to incidence and outcome. Little is known about sex differences in GBM at the disease phenotype and genetical/molecular level. This review focuses on a deep understanding of the pathophysiology of GBM, including hormones, metabolic pathways, the immune system, and molecular changes, along with differences between men and women and how these dimorphisms affect disease outcome. The information analyzed in this review shows a greater incidence and worse outcome in male patients with GBM compared with female patients. We highlight the protective role of estrogen and the upregulation of androgen receptors and testosterone having detrimental effects on GBM. Moreover, hormones and the immune system work in synergy to directly affect the GBM microenvironment. Genetic and molecular differences have also recently been identified. Specific genes and molecular pathways, either upregulated or downregulated depending on sex, could potentially directly dictate GBM outcome differences. It appears that sexual dimorphism in GBM affects patient outcome and requires an individualized approach to management considering the sex of the patient, especially in relation to differences at the molecular level.
Spinal cord injury is a serious damage to the spinal cord that can lead to life-long disability. Based on its etiology, spinal cord injury can be classified as traumatic or non-traumatic spinal cord injury. Furthermore, the pathology of spinal cord injury can be divided into two phases, a primary injury phase, and a secondary injury phase. The primary spinal cord injury phase involves the initial mechanical injury in which the physical force of impact is directly imparted to the spinal cord, disrupting blood vessels, axons, and neural cell membranes. After the primary injury, a cascade of secondary events begins, expanding the zone of neural tissue damage, and exacerbating neurological deficits. Secondary injury is a progressive condition characterized by pro-inflammatory cytokines, reactive oxygen species, oxidative damage, excitatory amino acids such as glutamate, loss of ionic homeostasis, mitochondrial dysfunction, and cell death. This secondary phase lasts for several weeks or months and can be further subdivided into acute, subacute, and chronic. One of the most frequent and devastating complications developed among the spinal cord injury population is cognitive impairment. The risk of cognitive decline after spinal cord injury has been reported to be 13 times higher than in healthy individuals. The exact etiology of this neurological complication remains unclear, however, many factors have been proposed as potential contributors to the development of this disorder, such as concomitant traumatic brain injury, hypoxia, anoxia, autonomic dysfunction, sleep disorders such as obstructive sleep apnea, body temperature dysregulation, alcohol abuse, and certain drugs. This review focuses on a deep understanding of the pathophysiology of spinal cord injury and its relationship to cognitive impairment. We highlight the main mechanisms that lead to the development of this neurological complication in patients with spinal cord injury.
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