10 research outputs found
Correction: Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury
Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition
xiii, 348 hlm.; 21 cm
Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson\u27s disease.
Premarin Reduces Neurodegeneration and Promotes Improvement of Function in an Animal Model of Spinal Cord Injury
Spinal cord injury (SCI) causes significant mortality and morbidity. Currently, no FDA-approved pharmacotherapy is available for treating SCI. Previously, low doses of estrogen (17β-estradiol, E2) were shown to improve the post-injury outcome in a rat SCI model. However, the range of associated side effects makes advocating its therapeutic use difficult. Therefore, this study aimed at investigating the therapeutic efficacy of Premarin (PRM) in SCI. PRM is an FDA-approved E2 (10%) formulation, which is used for hormone replacement therapy with minimal risk of serious side effects. The effects of PRM on SCI were examined by magnetic resonance imaging, immunofluorescent staining, and western blot analysis in a rat model. SCI animals treated with vehicle alone, PRM, E2 receptor antagonist (ICI), or PRM + ICI were graded in a blinded way for locomotor function by using the Basso–Beattie–Bresnahan (BBB) locomotor scale. PRM treatment for 7 days decreased post-SCI lesion volume and attenuated neuronal cell death, inflammation, and axonal damage. PRM also altered the balance of pro- and anti-apoptotic proteins in favor of cell survival and improved angiogenesis and microvascular growth. Increased expression of estrogen receptors (ERs) ERα and ERβ following PRM treatment and their inhibition by ER inhibitor indicated that the neuroprotection associated with PRM treatment might be E2-receptor mediated. The attenuation of glial activation with decreased inflammation and cell death, and increased angiogenesis by PRM led to improved functional outcome as determined by the BBB locomotor scale. These results suggest that PRM treatment has significant therapeutic implications for the improvement of post-SCI outcome
Inhibition of Calpain Activation Protects MPTP-Induced Nigral and Spinal Cord Neurodegeneration, Reduces Inflammation, and Improves Gait Dynamics in Mice
Low dose Estrogen Prevents Neuronal Degeneration and Microglial Reactivity in an Acute Model of Spinal Cord Injury: Effect of Dosing, Route of Administration, and Therapy Delay
Cell-Permeable Calpain Inhibitor SJA6017 Provides Functional Protection to Spinal Motoneurons Exposed to MPP+
Inhibition of Cysteine Proteases in Acute and Chronic Spinal Cord Injury
Spinal cord injury (SCI) is a serious neurological disorder that debilitates mostly young people. Unfortunately, we still do not have suitable therapeutic agents for treatment of SCI and prevention of its devastating consequences. However, we have gained a good understanding of pathological mechanisms that cause neurodegeneration leading to paralysis or even death following SCI. Primary injury to the spinal cord initiates the secondary injury process that includes various deleterious factors for ultimate activation of different cysteine proteases for degradation of cellular key cytoskeleton and other crucial proteins for delayed death of neurons and glial cells at the site of SCI and its penumbra in different animal models. An important aspect of SCI is the increase in intracellular free Ca2+ concentration within a short time of primary injury. Various studies in different laboratories demonstrate that the most important cysteine protease for neurodegeneration in SCI is calpain, which absolutely requires intracellular free Ca2+ for its activation. Furthermore, other cysteine proteases, such as caspases and cathepsin B also make a contribution to neurodegeneration in SCI. Therefore, inhibition of cysteine proteases is an important goal in prevention of neurodegeneration in SCI. Studies showed that individual inhibitors of cysteine proteases provided significant neuroprotection in animal models of SCI. Recent studies suggest that physiological hormones, such as estrogen and melatonin, can be successfully used for prevention of neurodegeneration and preservation of motor function in acute SCI as well as in chronic SCI in rats